Pediatric Nutrition in Practice II

Pediatric Nutrition in

Practice

Editor

Berthold Koletzko Munich

Co-Editors

Peter Cooper Johannesburg Maria Makrides North Adelaide Cutberto Garza Boston, Mass. Ricardo Uauy Santiago de Chile Weiping Wang Shanghai

70 figures, 29 in color, and 119 tables, 2008

Basel • Freiburg • Paris • London • New York • Bangalore • Bangkok • Shanghai • Singapore • Tokyo • Sydney

III Berthold Koletzko Peter Cooper Ricardo Uauy University of Munich Department of Paediatrics INTA Dr. von Hauner Children’s Hospital University of the Witwatersrand & University of Chile Lindwurmstr. 4 Johannesburg Hospital Casilla 138-11 DE–80337 Munich (Germany) Johannesburg 2000 (South Africa) Santiago de Chile (Chile)

Maria Makrides Weiping Wang Child Nutrition Research Centre Fudan University University of Adelaide 138 Yi Xue Yuan Road Women’s & Children’s Hospital 200032 Shanghai (China) 72 King William Road North Adelaide, S.A. 5006 (Australia)

Cutberto Garza Boston College Chestnut Hill, MA 02467 (USA)

Library of Congress Cataloging-in-Publication Data

Pediatric nutrition in practice / editor, Berthold Koletzko ; co-editors, Peter Cooper ... [et al.]. p. ; cm. Includes bibliographical references and indexes. ISBN 978-3-8055-8477-7 (soft cover : alk. paper) 1. Children--Nutrition--Handbooks, manuals, etc. I. Koletzko, B. (Berthold) II. Cooper, Peter, 1951 Sept. 12- [DNLM: 1. Child Nutrition Physiology. WS 130 P3713 2008] RJ206.P3635 2008 618.92--dc22 2008023394

Disclaimer. The statements, options and data contained in this publication are solely those of the individual authors and contributors and not of the publisher and the editor(s). The appearance of advertisements in the book is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher, the editor(s) and Nestlé Nutrition Institute disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content. Drug Dosage. The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any change in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.

Contents

List of Contributors ...... IX Foreword ...... XIII Preface ...... XIV

1 General Aspects of Childhood Nutrition

1.1 Child Growth Kim Fleischer Michaelsen ...... 1 1.2 Nutritional Assessment 1.2.1 Clinical Evaluation and Anthropometry John W.L. Puntis ...... 6 1.2.2 History and Dietary Intake Roxana Valdes-Ramos ...... 13 1.2.3 Use of Technical Measurements in Nutritional Assessment Hillary Burdette ؒ Babette Zemel ؒ Virginia A. Stallings ...... 17 1.2.4 Use of Laboratory Measurements in Nutritional Assessment Ryan Himes ؒ Robert Shulman...... 21 1.3 Nutritional Needs 1.3.1 Nutrient Intake Values: Concepts and Applications Berthold Koletzko ...... 27 1.3.2 Energy Requirements of Infants, Children and Adolescents Nancy Butte ...... 31 1.3.3 Protein Paul Pencharz ؒ Rajavel Elango ...... 37 1.3.4 Digestible and Indigestible Carbohydrates C. Lawrence Kien ...... 42 1.3.5 Fats Patricia Mena ؒ Ricardo Uauy ...... 47 1.3.6 Fluid and Electrolytes George J. Fuchs ...... 52

V 1.3.7 Vitamins and Trace Elements Noel Solomons ...... 57 1.4 Physical Activity: Impact on Child Health and Nutritional Needs Robert M. Malina...... 62 1.5 Early Nutrition and Long-Term Health Berthold Koletzko ...... 67 1.6 Food Safety Hildegard Przyrembel ...... 71 1.7 Gastrointestinal Development, Nutrient Digestion and Absorption Michael J. Lentze ...... 76 1.8 Gut Microbiota in Infants Seppo Salminen ؒ Mimi Tang ...... 80

2 Nutrition of Healthy Infants, Children and Adolescents

2.1 Breastfeeding Kim Fleischer Michaelsen ...... 85 2.2 Formula Feeding Dominique Turck ...... 90 2.3 Marketing of Breast-Milk Substitutes Vinodini Reddy ...... 98 2.4 Complementary Foods Mary Fewtrell ...... 102 2.5 Allergy Prevention through Early Nutrition Sibylle Koletzko ...... 106 2.6 Toddlers, Pre-School and School Children Hildegard Przyrembel ...... 110 2.7 Adolescence Luis A. Moreno ...... 114 2.8 Challenges in Transition from Childhood to Adult Age in Low Income Populations Mauro Fisberg ؒ Marcia Vitolo ؒ Mara Andréa Valverde ...... 118 2.9 Food Choices, Cultural Influences and Nutrition Transition – A Japanese Perspective Yuichiro Yamashiro ...... 122 2.10 Nutrition in Pregnancy and Lactation Renate L. Bergmann ؒ Karl E. Bergmann ...... 125 2.11 Vegetarian Diets Jules Tolboom ...... 130

3 Nutritional Challenges in Special Conditions and Diseases 3.1 Primary and Secondary Undernutrition Kraisid Tontisirin ؒ Lalita Bhattacharjee ...... 133 3.2 Iron Deficiency and Other Nutrient Deficiencies Noel W. Solomons ...... 137

VI 3.3 Enteral Nutrition Support Sanja Kolaček ...... 142 3.4 Parenteral Nutrition Support Berthold Koletzko ...... 147 3.5 Overweight and Obesity Martin Wabitsch ...... 151 3.6 Acute and Chronic Diarrhea Zulfiqar Bhutta ...... 155 3.7 HIV and AIDS Haroon Saloojee ؒ Peter Cooper ...... 162 3.8 Cholestatic Liver Diseases Edmond Rings ...... 168 3.9 Malabsorptive Disorders and Short Bowel Syndrome Olivier Goulet ...... 171 3.10 Celiac Disease Stefano Guandalini ...... 178 3.11 Food Intolerance and Allergy Ralf G. Heine ...... 184 3.12 Regurgitation and Gastroesophageal Reflux Tejas Mehta ؒ Benjamin Gold ...... 191 3.13 Feeding Disorders Richard M. Katz ...... 196 3.14 Preterm and Low Birthweight Infants Ekhard E. Ziegler ...... 200 3.14.1 Feeding the Low Birthweight Infant in a Resource-Restricted Environment Fredrick N. Were ...... 204 3.15 Diabetes Mellitus and Inborn Errors of Metabolism Hansjosef Böhles ...... 208 3.16 Hypercholesterolemia Berthold Koletzko ...... 214 3.17 Enteral Nutrition in Inflammatory Bowel Disease Anne M. Griffiths ؒ Megan Carricato ...... 219 3.18 Nutrition in Cystic Fibrosis Michael Wilschanski ...... 224 3.19 Heart Disease Michelle Steltzer ...... 229 3.20 Renal Disease Lesley Rees ؒ Jean-Pierre Guignard ...... 234 3.21 Anorexia Nervosa and Bulimia Nervosa Ascensión Marcos ...... 239 3.22 Hemato-Oncology John W.L. Puntis ...... 244 3.23 Intensive Care Jessie Hulst ؒ Hans Van Goudoever ...... 248

VII 4 Annex

4.1 The WHO Child Growth Standards Mercedes de Onis ...... 254 4.2 The CDC and Euro Growth Charts Ekhard Ziegler ...... 271 4.3 Reference Nutrient Intakes for Infants, Children and Adolescents Berthold Koletzko ؒ Maria Hermoso ...... 285 4.4 Feeding My Baby – Advice for Families Berthold Koletzko ؒ Katharina Dokoupil ...... 293 4.5 Increasing Dietary Energy and Nutrient Supply Berthold Koletzko ؒ Katharina Dokoupil ...... 296

5 Index Author Index ...... 298 Subject Index ...... 299

VIII

List of Contributors

Karl E. Bergmann Departments of Pediatrics and Obstetrics Megan Carricato Charité University Medicine Berlin Gastroenterology, Hepatology & Nutrition Augustenburger Platz 1 The Hospital for Sick Children DE–13353 Berlin (Germany) 555 University Avenue E-Mail [email protected] Toronto, Ont. M5G 1X8 (Canada) E-Mail [email protected] Renate L. Bergmann Departments of Pediatrics and Obstetrics Peter Cooper Charité University Medicine Berlin Department of Paediatrics Augustenburger Platz 1 University of the Witwatersrand & Johannesburg Hospital DE–13353 Berlin (Germany) Private Bag X39 E-Mail [email protected] Johannesburg 2000 (South Africa) E-Mail [email protected] Lalita Bhattacharjee National Food Policy Capacity Strengthening Programme Mercedes de Onis Food and Agriculture Organization of the United Nations Department of Nutrition House 37, Road 8, Dhanmondi R/A World Health Organization Dhaka 1205 (Bangladesh) Avenue Appia 20 E-Mail [email protected] CH–1211 Geneva 27 (Switzerland) E-Mail [email protected] Zulﬁ qar Ahmed Bhutta Husein Lalji Dewraj Professor & Chairman Katharina Dokoupil Department of Paediatrics & Child Health University of Munich Aga Khan University Dr. von Hauner Children’s Hospital Karachi 74800 (Pakistan) Lindwurmstrasse 4 E-Mail zulﬁ [email protected] DE–80337 Munich (Germany) E-Mail [email protected] Hansjosef Böhles Department of Pediatrics Rajavel Elango Zentrum für Kinder- und Jugendmedizin Physiology and Experimental Medicine Division Johann Wolfgang Goethe University Research Institute Theodor Stern Kai 7 The Hospital for Sick Children DE–60590 Frankfurt-am-Main (Germany) Toronto, Ont. M5G 1X8 (Canada) E-Mail [email protected] E-Mail [email protected]

Nancy F. Butte Mary Fewtrell USDA/ARS Children’s Nutrition Research Center Childhood Nutrition Research Centre Baylor College of Medicine UCL Institute of Child Health 1100 Bates Street 30 Guilford Street Houston, TX 77030 (USA) London WC1N 1EH (UK) E-Mail [email protected] E-Mail [email protected]

IX Mauro Fisberg Maria Hermosa Federal University of Sao Paulo University of Munich Nutrition Center, Sao Marcos University Dr. von Hauner Children’s Hospital Rua Botucatu 715, Vila Clementino Lindwurmstrasse 4 04023-062 Sao Paulo (Brazil) DE–80337 Munich (Germany) E-Mail ﬁ [email protected] E-Mail [email protected]

George J. Fuchs Ryan W. Himes Departments of Pediatric Gastroenterology, Hepatology Section of Pediatric Gastroenterology and Nutrition Texas Children’s Hospital University of Arkansas for Medical Sciences Baylor College of Medicine Mail stop 512-7 6621 Fannin St, CCC 1010.00 4301 West Markham Street Houston, TX 77030 (USA) Little Rock, AR 72205 (USA) E-Mail [email protected] E-Mail [email protected] Jessie M. Hulst Benjamin D. Gold Department of Pediatrics Division of Pediatrics and Microbiology, Sophia Children’s Hospital Pediatric Gastroenterology, Hepatology and Nutrition Erasmus Medical Center Emory University School of Medicine PO Box 2060 2015 Uppergate Drive NE NL–3000 CB Rotterdam (The Netherlands) Atlanta, GA 30322 (USA) E-Mail [email protected] E-Mail [email protected] Richard M. Katz Olivier Goulet Mount Washington Pediatric Hospital Hôpital Necker – Enfants Malades 1708 West Rogers Avenue 149 Rue de Sèvres Baltimore, MD 21209 (USA) FR–75743 Paris Cedex 15 (France) E-Mail [email protected] E-Mail [email protected] Craig Lawrence Kien Anne M. Griﬃ ths E203 Given Medical Building, Given Room C417 Hospital for Sick Children University of Vermont 555 University Avenue 89 Beaumont Avenue Toronto, Ont. M5G 1X8 (Canada) Burlington, VT 05405 (USA) E-Mail anne.griﬃ [email protected] E-Mail [email protected]

Stefano Guandalini Sanja Kolaček Pediatric Gastroenterology, MC 4065 Department of Pediatrics University of Chicago Children’s Hospital Zagreb 5839 South Maryland Avenue Referral Center for Pediatric Gastroenterology & Nutrition Chicago, IL 60637 (USA) Klaićeva 16 E-Mail [email protected] CRO–10000 Zagreb (Croatia) E-Mail [email protected] Jean-Pierre Guignard Lausanne University Medical School Berthold Koletzko CHUV-BP 11 University of Munich CH–1011 Lausanne (Switzerland) Dr. von Hauner Children’s Hospital E-Mail [email protected] Lindwurmstrasse 4 DE–80337 Munich (Germany) Ralf G. Heine E-Mail oﬃ [email protected] Department of Gastroenterology & Clinical Nutrition Royal Children’s Hospital, Melbourne Sibylle Koletzko University of Melbourne University of Munich Parkville, Vic. 3052 (Australia) Dr. von Hauner Children’s Hospital E-Mail [email protected] Lindwurmstrasse 4 DE–80337 Munich (Germany) E-Mail [email protected]

X Michael J. Lentze John W.L. Puntis Zentrum für Kinderheilkunde Department of Gastroenterology University of Bonn Room 142 B Floor, Clarendon Wing Adenauerallee 119 General Infi rmary at Leeds DE–53113 Bonn (Germany) Belmont Grove E-Mail [email protected] Leeds LS2 9NS (UK) E-Mail [email protected] Ascensión Marcos Immunonutrition Research Group Vinodini Reddy Department Metabolism and Nutrition Nutrition Consultant Instituto del Frío C/José Antonio Novais, 10 503 Mount Meru Apt. ES–28040 Madrid (Spain) Banjara Hills, Road No. 5 E-Mail [email protected] Hyderabad 500034 (India) E-Mail [email protected] Robert M. Malina 10735 FM 2668 Lesley Rees Bay City, TX 77414 (USA) Renal Offi ce E-Mail [email protected] Gt Ormond St Hospital for Sick Children NHS Trust Gt Ormond Street Tejas R. Mehta London WC1N 3JH (UK) Divison of Pediatric Gastroenterology, E-Mail [email protected] Hepatology and Nutrition Emory University School of Medicine Edmond H.H.M. Rings 2015 Uppergate Dr., NE Department of Pediatrics Atlanta, GA 30322 (USA) Beatrix Children’s Hospital E-Mail tejas_ [email protected] University Medical Center University of Groningen Patricia Mena POB 30.001 INTA, University of Chile NL–9700 RB Groningen (The Netherlands) Casilla 138-11 E-Mail [email protected] Santiago de Chile (Chile) E-Mail [email protected] Seppo Salminen Functional Food Forum Kim Fleischer Michaelsen University of Turku Departments of Paediatric Nutrition FN–20014 Turku (Finland) and Human Nutrition, Faculty of Life Sciences E-Mail seppo.salminen@utu.fi University of Copenhagen Rolighedsvej 30 Haroon Saloojee DK–1958 Frederiksberg C (Denmark) Department of Paediatrics E-Mail [email protected] University of the Witwatersrand & Johannesburg Hospital Luis A. Moreno Private Bag X39 Escuela Universitaria de Ciencias de la Salud Johannesburg 2000 (South Africa) Universidad de Zaragoza E-Mail [email protected] C/Domingo Miral s/n ES–50009 Zaragoza (Spain) Robert J. Shulman E-Mail [email protected] Children’s Nutrition Research Center 1100 Bates Avenue, CNRC 8072 Paul B. Pencharz Houston, TX 77030 (USA) Departments of Paediatrics and Nutritional Sciences E-Mail [email protected] Division of Gastroenterology, Hepatology and Nutrition Hospital for Sick Children Noel W. Solomons 555 University Avenue Scientifi c Director Toronto, Ont. M5G 1X8 (Canada) CeSSIAM E-Mail [email protected] 17a Avenida Marisca No. 16–89, Zona 11 Guatemala City, 01011 (Guatemala) Hildegard Przyrembel E-Mail [email protected] Federal Institute for Risk Assessment Thielallee 88–92 DE–14195 Berlin (Germany) E-Mail [email protected]

XI Virginia A. Stallings Mara Andréia Valverde Division of Gastroenterology, Hepatology and Nutrition Applied Human Nutrition Children’s Hospital of Philadelphia University of São Paulo 34th and Civic Center Blvd. R. Nilo, 241 apto: 52 Aclimação Philadelphia, PA 19104 (USA) 01533-010 São Paulo SP (Brazil) E-Mail [email protected] E-Mail [email protected]

Michelle M. Steltzer Johannes B. van Goudoever Department of Pediatrics Division of Neonatology, Department of Pediatrics Division of Pediatric Cardiology Sophia Children’s Hospital Children’s Hospital of Wisconsin Erasmus Medical Center Herma Heart Center POB 2060 Medical College of Wisconsin NL–3000 CB Rotterdam (The Netherlands) 8701 Watertown Plank Road E-Mail [email protected] Milwaukee, WI 53226 (USA) E-Mail [email protected] Marcia Regina Vitolo Public Health Department/Nutrition Mimi Tang Universidade Federal de Ciências da Saúde de Department of Allergy and Immunology Porto Alegre (UFCSPA) Royal Children’s Hospital Rua Sarmento Leite 245 Melbourne (Australia) 90050-170 Porto Alegre RS (Brazil) E-Mail [email protected] E-Mail [email protected]

Jules J.M. Tolboom Martin Wabitsch Paediatric Gastro-Enterologist Division of Pediatric Endocrinology Principal Consultant in Paediatrics Diabetes and Obesity Unit Radboud University Medical Centre, 833 Department of Pediatrics and Adolescent Medicine University Medical Centre St Radboud, 833 University of Ulm POB 9101 Eythstrasse 24 NL–6500 HB Nijmegen (The Netherlands) DE–89075 Ulm (Germany) E-Mail [email protected] E-Mail [email protected]

Kraisid Tontisirin Fredrick N. Were Institute of Nutrition Department of Paediatrics Mahidol University Salaya University of Nairobi Nakhon Pathom 73170 (Thailand) Kenyatta National Hospital Campus E-Mail [email protected] POB 20956-00202 Nairobi (Kenia) Dominique Turck E-Mail [email protected] Unité de Gastro-Entérologie, Hépatologie et Nutrition Clinique de Pédiatrie Michael Wilschanski Hôpital Jeanne de Flandre Pediatric Gastroenterology and Nutrition Unit 2, avenue Oscar Lambret Hadassah University Hospitals FR–59037 Lille (France) Jerusalem (Israel) E-Mail [email protected] E-Mail [email protected]

Ricardo Uauy Yuichiro Yamashiro INTA Santiago Probiotic Research Laboratory Santiago de Chile (Chile) Juntendo University Graduate School of Medicine E-Mail [email protected] 3rd Floor, 2-9-8 Hongo, Bunkyo-ku Tokyo 113-0033 (Japan) Roxana Valdes-Ramos E-Mail [email protected] Facultad de Medicina Universidad Autonoma del Estado de Mexico Ekhard E. Ziegler Jesus Carranza esq. Paseo Tollocan Department of Pediatrics Col. Moderna de la Cruz University of Iowa 50180, Toluca, Edo. Mex. (Mexico) A-136 MTF, 2501 Crosspark Road E-Mail [email protected] Coralville, IA 52241-8802 (USA) E-Mail [email protected]

XII

Foreword

The Nestlé Nutrition Institute (NNI) was created an accredited e-learning course, available online to provide healthcare professionals with up-to- at www.nestlenutrition-institute.org, which will date information on nutrition and nutrition-re- further increase its utility for pediatricians. lated disorders in order to promote health for The NNI is deeply indebted to the editor of children and adults, in particular those who have this book, Prof. Bert Koletzko from the University specific needs, based on the latest medical and of Munich, Germany, for his outstanding work in scientific breakthroughs. establishing and coordinating the content of Pe- For more than 60 years the NNI has contrib- diatric Nutrition in Practice. We also wish to uted to the continuing nutrition education of warmly thank the co-editors, Prof. Peter Cooper, health professionals. NNI’s activities comprise Johannesburg, South Africa; Dr. Maria Makrides, live events (e.g. congresses, workshops), written Adelaide, Australia; Prof. Ricardo Uauy, Santiago publications, online programs, audio, video, or de Chile, Chile; Prof. Cutberto Garza, Boston, other electronic media. The vast majority of in- Mass., USA, and Prof. Weiping Wang, Shanghai, formation is also available online at www.nestle- China, for their great contribution to the prepa- nutrition-institute.org. ration of this book. Pediatric Nutrition in Practice is a handbook Prof. Ferdinand Haschke, MD, PhD comprising all relevant, practical reference infor- Chairman, Nestlé Nutrition Institute mation for the feeding of generally healthy in- Vevey, Switzerland fants, children and adolescents, and for nutri- Dr. Petra Klassen, PhD tional care in pediatric diseases. It is intended to D r . D e n i s B a r c l a y , P h D be used by pediatricians working in preventive Nestlé Nutrition Institute and curative services around the world, includ- Vevey, Switzerland ing both high- and low-income settings. The content of this book will also be transformed into

Preface

There is no other time in life when the provi- their knowledge, time and effort in preparing sion of appropriate nutrition is of greater impor- their chapters. It has been a great pleasure to work tance than during infancy and childhood. Dur- with the editorial production team at Karger Pub- ing this phase of life characterized by rapid lishers, who did a fantastic and very professional growth and development, an adequate amount job in producing a book of outstanding quality. and composition of substrates both in health and Finally, I gratefully acknowledge the generous fi- disease are of key importance for growth, func- nancial support of the Nestlé Nutrition Institute tional outcomes such as cognition and immune that covered a large portion of the production response, and long-term wellbeing. While a num- costs and will help to widely disseminate this ber of excellent textbooks on pediatric nutrition practical guide. With sincere thanks I also wish are available that provide detailed accounts on to highlight the fact that the Nestlé Nutrition In- the scientific and physiologic basis of nutrition as stitute and its representatives Petra Klassen-Wig- well as its application, busy physicians and other ger, Denis Barclay and Ferdinand Haschke sup- healthcare professionals often find it difficult to ported the editors in making their fully indepen- devote sufficient time to study elaborate and ex- dent choices on content, direction and the authors tensive books on just one aspect of their practice. of this book, and this is greatly appreciated in- Therefore, we decided to develop this compact deed. reference book to provide concise information to It is the sincere hope of the editors that this readers who seek quick guidance on practical rel- book will be useful to many healthcare profes- evant issues in the nutrition of infants, children sionals around the world, and that it may contrib- and adolescents. This book was developed with a ute to further enhancing the quality of feeding truly international perspective to address chal- for healthy infants and children, as well as en- lenges both in affluent and poorer populations, hancing the standards of nutritional care for sick which could only be achieved with the insightful children. We are very keen to have feedback on input of a global editorial board. I wish to thank this book from you, the readers, including sug- my co-editors very much indeed for their enthu- gestions on which aspects might be improved siastic help and support in developing this proj- even further in the future. Thank you very much ect. I am also most grateful to the authors from for your support! all parts of the world, who are renowned experts Berthold Koletzko, Munich in their fields, for their willingness to dedicate E-Mail [email protected] Koletzko B. (ed): Pediatric Nutrition in Practice. Basel, Karger, 2008, pp 1–5

1 General Aspects of Childhood Nutrition

1.1 Child Growth Kim Fleischer Michaelsen

Growth of the Healthy Child Key Words ؒ Stunting ؒ Wasting ؒ Obesity ؒ Growth monitoring -Insulin-like growth factor-I ؒ Weight ؒ Height ؒ From conception to adulthood, growth can be di -Body mass index ؒ Growth vided into periods: intrauterine, infancy, child hood, and adolescence. Each period has its own characteristic pattern and the mechanisms regu- Key Messages lating growth differ [1] ( fig. 1 ). Nutrition has its R Growth is a sensitive marker of health and nutri- strongest regulatory effect during early life, growth tional status throughout childhood hormone secretion plays an important role during R Growth monitoring is important both in children infancy and growth is modified by sex hormones with diseases and in healthy children during puberty. Insulin-like growth factor-I (IGF- R Early growth is associated with long-term develop- I) mediates the effect of growth hormone on ment and health R Breastfed infants have a slower growth velocity growth, but IGF-I can also be stimulated directly during infancy, which is likely to have beneficial by nutrients. Linear growth velocity and weight long-term effects gain is highest during the first few months after Copyright © 2008 S. Karger AG, Basel birth, with monthly increments of about 4 cm and 1 kg. Then growth velocity declines until the pubertal growth spurt, which is earlier in girls than Introduction in boys ( fig. 2 ). Age at puberty differs considerably between populations with later puberty in popula- Growth is the main characteristic of childhood, tions with a poor nutritional status. and a sensitive indicator of the child’s nutritional Different organs grow at very different rates status. Deviations in growth, especially reduced (fig. 3). The brain and, therefore, head circumfer- growth, are associated with an increased risk of ence grow mainly during the first 2 years of life, diseases both in the short- and long-term. Moni- with head circumference reaching about 80% of toring growth is therefore an important tool for adult values at the age of 2 years. Body fat mass, assessing the health and wellbeing of children, expressed as a percentage of body mass, increases especially in countries where other diagnostic from birth to about 6–9 months, then decreases tools are scarce. It is also an important tool in ad- until the age of about 5–6 years, after which there vanced clinical settings, but often it is not given is an increase again. These changes are reflected the necessary attention, to the detriment of more both in reference curves for body mass index sophisticated examinations. (BMI) and skinfolds ( fig. 4 ). cm cm/year 200 Sex steroids 24 Growth hormone 180 22 Fetal growth 1 + 2 + 3 20 160 1 + 2 18 140 16 Combined 120 14

100 12

80 10 Boy Infancy (1) Girl 8 60 Childhood (2) 6 40 4 20 Puberty (3) 2

0 0 –1 3 7 11 15 19 1357911 13 15 17 19 Age, years Age, years

Fig. 1. The infancy, childhood, puberty (ICP) growth Fig. 2. Linear growth velocity according to age in girls model by Karlberg [1]. and boys. Modified from Tanner et al. [6, 7].

Regulation of Growth Nutrition has a marked influence on growth, especially during the first years of life. Breastfed Many factors influence growth. Genetic influ- infants have a slower growth with regard to both ences are strong, but can be modified by many weight and length than formula-fed infants [3] , environmental factors. Ethnic differences are and it seems that this has beneficial effects in the likely to be caused more by environmental than long-term. It seems that a difference in protein genetic factors as preschool children from differ- intake may cause these differences. This is in line ent parts of the world seem to have the same with evidence suggesting that cow’s milk has a growth potential, as shown in the new WHO stimulating effect on linear growth, also in well- growth standards in which preschool children nourished populations [4] . Nutrition is also a key from different parts of the world have the same factor in the development of overweight and obe- growth pattern if they have optimal nutritional sity as discussed in Chapter 3.4. and socioeconomic conditions (see Chapter 4.1). Other studies show that the growth patterns of children from families moving to a country with Nutritional Problems Affecting Growth very different dietary and socioeconomic conditions change within one generation, and that the In a global perspective, the most common cause growth pattern in a population can change over of poor growth is an insufficient diet in which time, the so-called secular trend [2] . especially a lack of energy and some micronutri-

2 Pediatric Nutrition in Practice ents, e.g. zinc, is important. Protein deficiency can also affect growth, but protein deficiency without energy deficiency is not common among 160 malnourished children in developing countries and rare among malnourished patients in indus- 140 trialized countries. Undernutrition, low weight- for-age, can be caused by low height-for-age 120 Thymus (stunting), low weight-for-height (wasting or thinness), or a combination of these. In popula- 100 tions with poor nutrition, stunting is regarded as 80 a result of chronic malnutrition and wasting a re- Brain 1 sult of acute malnutrition, but in the individual 60 Liver this is often a simplification.

Many acute and chronic diseases result in % of adult weight Organ weight, 40 Heart poor appetite and eating difficulties and, conse- quently, malnutrition. Infections and diseases 20 Body weight with inflammation, such as autoimmune diseas- Testes es and cancers, are associated with anorexia. Psy- 0 chological problems, such as nonorganic failure 0 1 2 4 6 8 10 14 18 to thrive and eating disorders are also associated Age, years with anorexia and malnutrition. Obesity is characterized by an increased body fat mass, but as fat mass is too complicated to Fig. 3. Relative growth of different organs as percentage of adult body weight. Modified from Koletzko [8] . measure routinely, the BMI (weight/length 2 ) is commonly used to describe overweight and obesity [5] . Overweight children are often taller than children with normal weight until puberty, which low stature being associated with cardiovascular they typically reach earlier than normal weight disease and tall stature being associated with sev- children. Therefore, there are no major differenc- eral types of cancer. Early nutrition plays a role as es in height after puberty. described in Chapter 1.5. However, the mechanisms are not clear and there is only little information about the degree to which the deviations Growth and Long-Term Health in growth alone or the factors responsible for the deviation in growth are the cause of the increased There is strong evidence that marked deviations risk of disease later in life. from the average growth pattern, especially during early life, are associated with impaired development and increased risk of many non-com- Growth Monitoring municable diseases later in life. Examples are increased risk of cardiovascular disease in indi- Regular measurements of weight and height and viduals with low birthweight and increased risk plotting of weight curves including earlier mea- of type-2 diabetes and obesity in individuals with surements are important tools in monitoring the a high growth velocity during early life. Height as health of children in both the primary healthcare an adult is also associated with several diseases; system and in hospitals. Weight-for-age curves

Child Growth 3 30 27 25 97 97 90 20 25 75 90 15 23 14 50 75 12 21 25 50 9 10 19 8 25 7 3 10 17 6 3

Body mass index 15 5 Subscapular skinfold, mm 13 4

3 9 8 1357911131517 1357911131517 Age, years Age, years

Fig. 4. Reference charts (percentiles) for subscapular skinfold and body mass index for boys. Modified from Tanner and Whitehouse [9] and Nysom et al. [10].

are not sufficient. There is a need for both height- C o n c l u s i o n s for-age and either weight-for-height or BMI curves and calculation of present growth velocity • Regular measurements of weight and length/ to make a comprehensive evaluation. height, and plotting on growth charts, includ- With the development of software, easily avail- ing BMI, are important tools in monitoring able on the internet, e.g. www.who.int/childgrowth/ the health and nutritional status of both chil- software/en/, it has become very easy to enter dren with diseases and healthy children weight and length data, calculate percentiles and • Regular monitoring of growth in healthy chil- standard deviation scores, and plot the curves on dren should be performed by the primary a graph, so that parents will also be able to do the healthcare system, including the school health monitoring. system Surveillance, following trends of malnutrition and overweight and obesity in populations, is an important public health tool in monitoring the nutritional status of populations. It is often relevant to perform such surveillances both at the local, regional and national level.

4 Pediatric Nutrition in Practice References

1 Karlberg J: A biologically-oriented 4 Hoppe C, Molgaard C, Michaelsen KF: 7 Tanner JM, Whitehouse RH, Takaishi mathematical model (ICP) for human Cow’s milk and linear growth in indus- M: Standards from birth to maturity growth. Acta Paediatr Scand Suppl trialized and developing countries. for height, weight, height velocity, and

1989; 350: 70–94. Annu Rev Nutr 2006; 26: 131–173. weight velocity: British children, 1965.

2 Larnkjær A, Schrøder SA, Schmidt IM, 5 Cole TJ, Bellizzi MC, Flegal KM, Dietz II. Arch Dis Child 1966; 41: 613–635. et al: Secular change in adult stature WH: Establishing a standard definition 8 Koletzko B (ed): Kinderheilkunde und has come to a halt in northern Europe for child overweight and obesity world- Jugendmedizin, ed 13. Berlin, Springer,

and Italy. Acta Paediatr 2006; 95: 754– wide: international survey. BMJ 2000; 2007.

755. 320: 1240–1243. 9 Tanner JM, Whitehouse RH: Revised 3 Dewey KG, Peerson JM, Brown KH, et 6 Tanner JM, Whitehouse RH, Takaishi standards for triceps and subscapular al: Growth of breast-fed infants devi- M: Standards from birth to maturity skinfolds in British children. Arch Dis

ates from current reference data: a for height, weight, height velocity, and Child 1975; 50: 142–145. pooled analysis of US, Canadian, and weight velocity: British children, 1965. 10 Nysom K, Mo/lgaard C, Hutchings B, 1 European data sets. World Health Or- I. Arch Dis Child 1966; 41: 454–471. Michaelsen KF: Body mass index of 0 to ganization Working Group on Infant 45-y-old Danes: reference values and

Growth. Pediatrics 1995; 96: 495–503. comparison with published European reference values. Int J Obes Relat Metab Disord 2001;25:177–184.

Child Growth 5 Koletzko B. (ed): Pediatric Nutrition in Practice. Basel, Karger, 2008, pp 6–12

1 General Aspects of Childhood Nutrition

1.2 Nutritional Assessment

1.2.1 Clinical Evaluation and Anthropometry John W.L. Puntis

Nutritional Assessment Key Words ؒ Nutritional assessment ؒ Feeding history Anthropometry ؒ Growth ؒ Malnutrition Malnutrition impairs growth, in time leading to multisystem disease. Nutritional status reflects the balance between supply and demand and the Key Messages consequences of any imbalance. Nutritional as- R Nutritional assessment includes feeding history, sessment is therefore the foundation of nutrition- clinical examination, and anthropometry; basic heal care for children [1] . When judging the need matological and biochemical indices should also for nutritional support, an assessment must be be included if possible in order to identify specific made both of the underlying reasons for any feed- nutrient deficiencies R Careful measurement of growth status and refer- ing difficulties, and of current nutritional status. ence to standard growth charts is essential in order This process includes a detailed dietary history, to identify those children who are malnourished physical examination, anthropometry (weight, R Addition of skinfold thickness measurements and length; head circumference in younger children) mid-upper arm circumference allows estimation of with reference to standard growth charts [2] , and body composition; however, this is not often calcu- basic laboratory indices (cf. Chapter 1.2.4) if pos- lated in routine clinical practice R There are a number of different ways of defining sible. In addition, skinfold thickness and mid-up- malnutrition and no definition universally agreed per arm circumference measurements provide a on simple method for estimating body composition R Short-term malnutrition affects weight so that the [3] . child becomes thin (‘wasting’) R Long-term malnutrition leads to poor linear growth so that the child will have a low height for age (‘stunting’) Nutritional Intake R The point at which deteriorating nutritional status demands invasive intervention (tube feeding) in Questions regarding mealtimes, food intake and order to prevent adverse outcomes is unclear and difficulties with eating should be part of routine will depend on the underlying disease and the history taking, and give a rapid qualitative im- overall clinical status of the individual child R Serial measurements are required to monitor the pression of nutritional intake (cf. Chapter 1.2.2). effectiveness of nutritional intervention For a more quantitative assessment a detailed di- Copyright © 2008 S. Karger AG, Basel etary history must be taken which involves recording a food diary or (less commonly) a weighed food intake. This would usually be undertaken in • How many feeds are taken over 24 h? conjunction with an expert pediatric dietician. • How often are feeds offered – every 2, 3, 4 h? Use of compositional food tables or a computer • What is the volume of feed offered each time? software program allows these data to be ana- • How much feed is taken? lyzed so that a more accurate assessment of the • How long does this take? intake of energy and specific nutrients can be • Is anything else being added to the bottle? made. When considering whether such intakes For older children: are sufficient, reference can be made to dietary • How many meals and snacks are eaten each reference values (DRV) which provide estimates day? of the range of energy and nutrient requirements • What does the child eat at each meal and snack? in groups of individuals [4] . Many countries have (obtain a 1- or 2-day sample meal pattern) 1 their own values, and international values have • How do the parents describe their child’s ap- been published by the FAO/WHO/UNU. DRV petite? are based on the assumption that individual re- • Where does the child eat meals? quirements for a nutrient within a population • Are there family mealtimes? group are normally distributed and that 95% of • Are these happy and enjoyable situations? the population will have requirements within 2 • How much milk does the child drink? standard deviations of the mean (cf. Chapter • How much juice does the child drink? 1.3.1). In a particular individual, intakes above • How often are snacks/snack foods eaten? the reference nutrient intake are almost certainly (Further details are provided in Chapter 1.2.2). adequate, unless there are very high disease-induced requirements for specific nutrients, while intakes below the lower reference nutrient intake Basic Anthropometry: the Assessment of are almost certainly inadequate. Body Form

Accurate measurement and charting of weight Taking a Feeding History and height (‘length’ in children ! 85 cm, or unable to stand) is essential if malnutrition is to be A careful history is an important component of identified; clinical examination without charting nutritional assessment. Listed below are some of anthropometric measurements (‘eye-balling’) the questions and ‘cross-checks’ that are integral has been shown to be very inaccurate [5] . For pre- to an accurate feeding/diet history: mature infants up to 2 years of age, it is essential Infant: is the baby being breastfed or formula fed? to deduct the number of weeks born early from For breastfed infants: the actual (‘chronological’) age in order to derive • How often is the baby being fed and for how the ‘corrected’ age for plotting on growth charts. long on each breast? (check positioning and Head circumference should be routinely mea- technique) sured and plotted in children less than 2 years. • Are supplementary bottles or other foods of- Measurements should be made as follows. fered? Weight: For formula-fed infants: • Weigh infants ! 2 years naked • What type of formula? How is the feed made • Weigh older children only in light clothing up? (i.e. establish the final energy concentra- ( fig. 1 ) tion/100 ml) • Use self-calibrating or regularly calibrated • Is each feed freshly prepared? scales.

Clinical Evaluation and Anthropometry 7 Fig. 2. An infant measuring board; two people are required for accurate determination of length.

• Remove the child’s shoes • Ask the child to look straight ahead • Ensure that the heels, buttocks and shoulder blades make contact with the wall. Head circumference: • Use a tape measure that does not stretch • Find the largest measurement around the mid-forehead and occipital prominence. Mid-upper arm circumference: Fig. 1. Weigh older children only in light clothing using • Mark the mid-upper arm (halfway between the regularly maintained and calibrated scales. acromion of the shoulder and the olecranon of the elbow; fig 4), then use a non-stretch tape measure and take the average of three readings Length: at the mid-point of the upper arm (fig. 5). • If possible use an infant measuring board, Skinfold thickness: measuring mat (easily rolled and transported) • Pinch the skin between two fingers and apply or a measuring rod (see: www.miami-med. specialized skinfold calipers ( fig. 6 ); experi- com.Height_Measuring_Devices.htm) ence is needed to produce accurate and repeat- • Two people are required to use the measuring able measurements (see: http://healthsciences. board: one person holds the head against the qmuc.ac.uk/labweb/Equipment/skin_fold_ headboard, while the other straightens the calipers.htm); take triceps skinfold thickness knees and holds the feet against the moveable readings at the mid-upper arm using the re- foot board ( fig. 2 ). laxed non-dominant arm; the layer of skin and Height: subcutaneous tissue is pulled away from the • Use a stadiometer if possible (fig 3), a device underlying muscle, and readings are taken to for standing height measurement comprising 0.5 mm, 3 s after application of the calipers; a vertical scale with a sliding horizontal board measurements can also be taken at other sites or arm that is adjusted to rest on the top of the (see: http://www.cdc.gov/nchs/data/nhanes/ head nhanes3/cdrom/nchs/manuals/anthro.pdf).

8 Pediatric Nutrition in Practice 1

Fig. 3. A stadiometer should be used for accurate assessment of height.

4 5

Fig. 4. The mid-upper arm is the point halfway between the acromion of the shoulder and the olecranon of the elbow (marked with a pen). Fig. 5. To determine mid-upper arm circumference, take the average of three readings made with a non- stretch tape measure at the mid-upper arm point.

Growth that continues until puberty, a phase of growth lasting from adolescence onwards. During pu- Growth rate in infancy is a continuation of the berty, the major sex differences in height are intrauterine growth curve, and is rapidly decel- established, with a final height difference of erating up to 3 years. Growth in childhood is a around 12.5 cm between males and females. steady and slowly decelerating growth curve Growth charts are derived from measurements

Clinical Evaluation and Anthropometry 9 Head circumference: • Increases by 1 cm/month in the first year • Increases by 2 cm in the whole of the second year • Will be 80% of adult size by 2 years. (N.B.: growth rates vary considerably between children; these figures should be used in conjunction with growth charts).

Patterns of Growth Fig. 6. Triceps skinfold thickness taken with Harpenden calipers at the mid-upper arm allows estimation of fat Birthweight/centile is not always a good guide to energy stores and is useful for serial monitoring. genetic potential; some infants cross centile lines in the first few months of life (‘catch down’), but from then on continue to follow along a lower of many different children at different ages centile. The maximum weight centile achieved (cross-sectional data). Data for growth of chil- between 4 and 8 weeks is the best predictor of dren are distributed ‘normally’ (i.e. form a ‘bell- weight centile at 12 months. Infants born !10th shaped’ curve). These data can be expressed centile for gestational age may have either intra- mathematically as mean and standard devia- uterine growth retardation (IUGR), or be within tions (SD) from the mean. The centile lines de- the normal 10% of the population who fall below lineate data into percentages: the 50th centile this line. Long-standing IUGR results in low represents the mean (average); 25% of children weight, head circumference and length (‘sym- are below the 25th centile. The normal range metrically’ small); catch-up growth is unlikely. (approximately 8 2 SD from the mean) lies be- Infants with late IUGR are thin, but may have tween the 3rd and 97th centile. head circumference and length on higher centile, and subsequently show catch-up in weight. It should be noted that rates of growth vary in Normal Growth – Simple Rules of Thumb young children, and assessments should be based on serial measurements. Short-term energy defi- Approximate average expected weight gain for a cit will make a child thin (low weight for height = healthy term infant: wasting). Long-term energy deficit limits height • 200g/week in the first 3 months gain (and head/brain growth) causing stunting. • 130 g/week in the second 3 months Children who are chronically undernourished • 85 g/week in the third 3 months may be both thin and short. • 75 g/week in the fourth 3 months Assessment of linear growth potential: • Birthweight usually doubles by 4 months and • Plot height of both parents at 18-year-old end triples by 12 months. of centile chart Length: • Add together parental heights and divide by 2 • Increases by 25 cm in the first year • Add 7 cm (male child), subtract 7 cm (fe- • Increases by 12 cm in the second year male) = mid-parental height (MPH); MPH 8 • By 2 years roughly half of adult height is at- 8.5 cm (girl), or 8 10 cm (boy) = target height tained. centile range.

10 Pediatric Nutrition in Practice Table 1. Criteria for malnutrition

Obese Overweight Normal Mild Moderate Severe malnutrition malnutrition malnutrition

Height for age, % 90–95 85–90 <85 Weight for height, % >120 110–120 90–100 80–90 70–80 <70 Body mass index >30 >25

Anthropometric Indices and Definitions of Table 2. Wellcome classification of malnutrition 1 Malnutrition Marasmus <60% expected weight for age, no edema Weight-for-height compares a child’s weight with the average weight for children of the same height, Marasmic kwashiorkor <60% expected weight for age, edema present i.e.: actual weight/weight for height at the 50th centile. Kwashiorkor <60–80% expected weight for age, edema present For example, a 2.5-year-old girl: height = 88 cm; weight = 9 kg; 50th centile weight for a child who, Underweight <60–80% expected weight for at 88 cm, is on the 50th centile for height = 12 kg. age, no edema Weight for height is therefore 9/12 = 75% (‘moderate’ malnutrition). Weight-for-height can be expressed either as percent expected weight, or as ‘z’ score. The z er clinical signs that may have different etiologies. score is commonly used when statistical compar- Other nutrients such as iron, zinc and copper may ison is being made, as it enables children of dif- be deficient in addition to protein and energy. ferent sexes and ages to be compared. A value on The Wellcome classification of malnutrition is the 50th centile would have a z score of 0 whereas based on the presence or absence of edema and values on the 2nd and 98th centiles are –2 and +2 the bodyweight deficit ( table 2 ). SD, respectively. Mid-upper arm circumference provides a quick population screening tool for malnutrition; reference charts are available [6] . When to Intervene Body mass index is derived from weight in kilo- grams divided by the square of the height in me- Malnutrition is a continuum that starts with a nu- ters (kg/m 2); it is an alternative to ‘weight-for- trient intake inadequate to meet physiological re- height’ as an assessment of nutritional status [7] . quirements, followed by metabolic and functional alterations and, in due course, by impairment of body composition. Malnutrition is difficult to de- Classifications of Malnutrition fine and assess because of insensitive assessment tools and the challenges of separating the impact There is no single, universally agreed on defini- of malnutrition from that of the underlying dis- tion of malnutrition in children [8] , but the crite- ease on markers of malnutrition (e.g. hypoalbu- ria shown in table 1 are commonly used. Classifi- minemia is a marker of both malnutrition and se- cation does not define a specific disease, but rath- vere inflammation) and on outcome. Nutritional

Clinical Evaluation and Anthropometry 11 intervention may be indicated both to prevent height velocity !5 cm/year and to reverse malnutrition. In general the sim- or plest intervention should be followed if necessary decrease in height velocity of at least 2 cm by those of increasing complexity. For example, from the preceding year during early to mid- energy-dense foods and calorie supplements be- puberty fore progressing to tube feeding (cf. Chapter 3.3). Parenteral nutrition should be reserved for children when nutrient needs cannot be met by en- Conclusions teral feeding (cf. Chapter 3.4). When simple measures aimed at increasing energy intake by mouth • A detailed feeding history should be part of are ineffective, tube feeding should be considered routine nutritional assessment [9] ; the following are suggested criteria. • Expert dietetic assistance is required for more • Impaired energy consumption objective assessment of nutritional intake, and Usually 50–60% of recommended daily for appropriate further management amount despite high-energy supplements • Accurate assessment of growth by careful plus measurement and reference to standard • Severe and deteriorating wasting growth charts is essential to define and moni- Weight for height 1 2 SD below the mean tor nutritional status plus • Malnutrition is a dynamic and complex pro- Skinfold thickness ! 3rd centile cess without clearly agreed definitions and/or • The clinical status and particular needs of • Depressed linear growth each individual child require careful evalua- Fall in height of 1 0.3 SD/year tion when planning nutritional support or

References

1 Olsen IE, Mascarenhas MR, Stallings 3 Parker L, Reilly JJ, Slater C, et al: 6 Frisancho AR: New norms of upper VA: Clinical assessment of nutritional Validity of six field and laboratory limb fat and muscle areas for assess- status; in Walker WA, Watkins JB, methods for measurement of body ment of nutritional status. Am J Clin

Duggan C (eds): Nutrition in Pediatrics. composition in boys. Obes Res 2003; 11: Nutr 1981; 34: 2540–2545. London, Decker, 2005, pp 6–16. 852–858. 7 Hall DMB, Cole TJ: What use is the

2 Wright CM: The use and interpretation 4 www.britishnutrition.org.uk. BMI? Arch Dis Child 2006; 91: 283–286.

of growth charts. Curr Paediatr 2002; 5 Cross JH, Holden C, MacDonald A, et 8 Raynor P, Rudolf MCJ: Anthropometric

12: 279–282. al: Clinical examination compared indices of failure to thrive. Arch Dis

with anthropometry in evaluating nu- Child 2000; 82: 364–365.

tritional status. Arch Dis Child 1995; 9 Booth IW: Enteral nutrition in child-

72: 60–61. hood. Br J Hosp Med 1991; 46: 112–113.

12 Pediatric Nutrition in Practice Koletzko B. (ed): Pediatric Nutrition in Practice. Basel, Karger, 2008, pp 13–16

1 General Aspects of Childhood Nutrition

1.2 Nutritional Assessment

1.2.2 History and Dietary Intake Roxana Valdes-Ramos 1

Key Words quately applied and interpreted can provide use- Health history ؒ Medical history ؒ Dietary intake ؒ ful guidance for identifying inadequate dietary Nutritional status supplies in individuals or populations.

Key Messages History R The most complete history of health and disease will shed light on a child’s nutritional risk A medical history can be obtained from hospital R Adequate assessment of dietary intake allows us to records or the family physician if there is a regu- identify deficiencies and abnormalities lar attendance at medical services, but usually the Copyright © 2008 S. Karger AG, Basel clinician needs to interview the child and caregivers to obtain information on the child and family history. It is important to identify any fact Introduction that may affect the child’s nutritional status, such as disease of parents or other family members, Assessement of nutritional status and dietary in- course of pregnancy and childbirth, use of medi- take is always related to the patient’s history; his- cations and nutritional supplements including tory of health and disease and of the family. It is herbal and traditional remedies. Growth charts not an easy task to identify all the nutritional risk should be gathered. Social and economic infor- factors that may be present in a given patient, mation should also be obtained in order to estab- particularly for the untrained clinician. Some of lish household food availability (including prepa- this history can be obtained from hospital or ration and distribution within the family), access family physician records, but usually one has to to health services, cultural and religious habits. rely on parental information that may vary with The importance of the information will depend educational background and cultural traditions. on the age of the child and the closeness of the Cues and questions may be used to prompt pa- possible effect; for example a grandparent’s his- tient’s answers. Information from caregivers is tory of hypertension may not directly affect an essential to evaluate small children, whereas old- infant, but it is definitely important for an obese er children and adolescents can provide adequate adolescent. Table 1 lists the most important his- information in most cases. Dietary intake assess- torical information relative to nutritional status ment methods have limited accuracy, but if ade- in children [1, 2] . Table 1. Historical information relative to nutritional status in children

Age group Information requested

Infants Prenatal and postnatal disease history (0–12 months) Pattern of lactation or formula feeding (frequency, duration of each session, position, abnormalities and diseases) Use of pacifier or thumb Age and pattern of weaning Unusual or abnormal feeding behaviors Parents’ or infant’s history of food allergies Use of supplements and medications Frequency and appearance of stools and urine Age and condition at birth (preterm, term, post-term; large, appropriate or small for gestational age, low birthweight, Apgar or Silverman) Growth charts (weight and length for age, head circumference) Parents’ psychological status Reflexes (sucking, extrusion, chewing, swallowing, tongue movement) Neurological development (rolling, sitting, crawling, walking, hand-eye-mouth control) Daycare Position among siblings Toddlers (1–3 years) Feeding skills and Physical activity level preschoolers (3–5 years) Food allergies, intolerances, aversion, fads, unusual habits Socioeconomic condition (availability and distribution of food) Climate and altitude (for iron levels) Hunger and satiety cues Pica Number of meals, snacks and daycare feeding Parents’ weight status or body mass index Previous and recurrent diseases Food preparation habits (who, where, how) Schoolchildren Family history of disease (6–10 years) Unusual weight gain or loss Appetite Adolescents Sexual maturation (11–21 years) (development of sexual characteristics, age at menarche in females) Addictions (alcohol, tobacco, drugs) Psychological health Body image and perception Physical activity patterns Dieting behavior Sexual activity Pregnancy or lactation

For each age group, the information requested for the previous age group should also be considered.

14 Pediatric Nutrition in Practice Table 2. Summary of dietary assessment methods

Method Advantages Disadvantages Uses

24-hour recall Fast Not precise Schoolchildren Easy to apply Gives a snap-shot and adolescents Depends on memory Underestimates intake Usual diet Easy to apply Inaccurate Toddlers to Depends on memory adolescents 3- to 7-day record Accurate Needs good participation All children Good for habitual diet Training required 1 Food frequency Gives data over long Time-consuming depending on the food list Schoolchildren periods of time Not very good for specific nutrients and adolescents Overestimates intake Checklist Fast Only for food groups All children Easy to apply Scores/indexes For very specific purposes and age-groups Need validation

Dietary Intake protocol is particularly useful in assessing larger population groups, whereas in individ- Dietary intake can be evaluated by various meth- uals, both day-to-day variations in consump- ods, depending on the age of the child and the tion, as well as errors in recollection often lim- kind of information needed. it the conclusions that can be drawn. The Infant’s diets are simple and easy to evaluate method tends not to be very useful in young through a prospective protocol of all foods con- children, since their intake usually has large sumed over a period of 24 h or 3 days, or a retro- day-to-day variations. spective recall protocol over the last 24 h which • A prospective 3- or 7-day record of all food the mother or caretaker can fill out on their own, and drinks consumed registered by the child or which can be obtained through questions from and/or caretaker is more informative than the the healthcare professional. 24-hour recall. It should include one weekend Children may need the help of a parent or or festive day which may lead to different food caretaker to complete any of the dietary intake choices. methods. Several options for dietary assessment • In a food-frequency protocol the subject re- are available [3–6] : ports the number of food and drink portions • A 24-hour recall protocol, in which the child consumed from a predetermined list of items, is asked to list all the foods and drinks con- during a defined time period, e.g. 1 week, the sumed during the 24 h (including approxi- protocol should define portion sizes or weights. mate weight or size of portions, the number of While a food-frequency protocol does not portions consumed, as well as recipes in the provide precise intake information, it is very case of homemade products). The validity de- useful to identify certain dietary patterns such pends on the child’s memory. A 24-hour recall as the exclusion of specific food groups.

History and Dietary Intake 15 • A food checklist is similar to the food-fre- C o n c l u s i o n s quency protocol but uses a shorter food list and is targeted to specific food groups or nu- • Take a detailed history of the patient’s diet and trients [7–11] . associated factors The data obtained from any of these methods • Identify food availability and household dis- need to be interpreted to assess food and nutrient tribution patterns intakes. While the exclusion of certain foods or • Evaluate family relationships and attitudes to- unbalanced dietary patterns may be quickly de- wards food and nutrition tected by an experienced dietician or clinician re- • Use a combination of two or more dietary as- viewing the protocol, quantitative assessments sessment methods and the calculation of nutrient intakes require • Dietary intakes can be assessed by 24-hour re- further calculations based on food composition call protocols or by prospective dietary re- tables or databases, usually with dedicated soft- cords obtained over 3–7 days, including 1 ware programs [12] , and the comparison to refer- weekend day ence intake values for age and gender. Such an analysis is time-consuming and should be used with clear questions and indications only. Table 2 summarizes relevant information on the most common dietary assessment methods.

References

1 Rolfes SR, DeBruyne LK, Whitney EN: 5 Knol LL, Haughton B, Fitzhugh EC: 9 Moore L, Tapper K, Denney A, Cooper Life Span Nutrition. Conception Food group adherence scores assess A: Development and testing of a com- through Life, ed 2. East Windsor, food patterns compared to US Depart- puterized 24-h recall questionnaire Wadsworth, 1998, pp 18–32. ment of Agriculture Food Guide. J Am measuring fruit and snack consump-

2 Avila-Rosas H, Tejero-Barrera E, Val- Diet Assoc 2006; 106: 1201–1208. tion among 9–11 year olds. Eur J Clin

des-Ramos R: Evaluacion del estado de 6 Zoellner J, Anderson J, Gould SM: Nutr 2005; 59: 809–816. nutricion (nutritional status evalua- Comparative validation of a bilingual 10 Lanigan JA, Wells JC, Lawson MS, et al: tion); in Casanueva E, Kaufer-Howitz interactive multimedia dietary assess- Number of days needed to assess

M, Perez-Lizaur AB, Arroyo P (eds): ment tool. J Am Diet Assoc 2005; 105: energy and nutrient intake in infants Nutriologia Médica (Medical Nutri- 1206–1214. and young children between 6 months tion), ed 2. Mexico City, Editorial 7 Huybrechts J, De Bacquer D, Matthys and 2 years of age. Eur J Clin Nutr

Médica Panamericana, 2001, pp 593– C, et al: Validity and reproducibility of 2004; 58: 745–750. 672. a semi-quantitative food-frequency 11 Sjoberg A, Hulthen L: Assessment of 3 Srivastava N, Sandhu A: Infant and questionnaire for estimating calcium habitual meal pattern and intake of child feeding index. Indian J Pediatr intake in Belgian preschool children. foods, energy and nutrients in Swedish

2006; 73: 767–770. Br J Nutr 2006; 95: 802–816. adolescent girls: comparison of diet 4 Kranz S, Harman T, Siega-Riz AM, 8 Williams PL, Innis SM: Food frequency history with 7-day record. Eur J Clin

Herring AH: A diet quality index for questionnaire for assessing infant iron Nutr 2004; 58: 1181–1189.

American preschoolers based on cur- nutrition. Can J Diet Pract Res 2005; 66: 12 Willett W: Nutritional Epidemiology, rent dietary intake recommendations 176–182. ed 2. New York, Oxford University and an indicator of energy balance. Press, 1998, pp 50–173.

J Am Diet Assoc 2006; 106: 1594–1604.

16 Pediatric Nutrition in Practice Koletzko B. (ed): Pediatric Nutrition in Practice. Basel, Karger, 2008, pp 17–20

1 General Aspects of Childhood Nutrition

1.2 Nutritional Assessment

1.2.3 Use of Technical Measurements in Nutritional Assessment

Hillary Burdette ؒ Babette Zemel ؒ Virginia A. Stallings

Key Words mating daily energy needs for optimal growth Resting energy expenditure ؒ Dual energy X-ray and development. This is especially important in -absorptiometry ؒ Indirect calorimetry ؒ Body children with health conditions causing under composition nutrition or obesity. However, the energy needs of such children can be difficult to estimate [1] . Resting energy expenditure (REE) represents a Key Messages large portion of the energy needed each day. The R Accurate nutritional assessment should be an inte- measurement of REE using indirect calorimetry gral part of pediatric care and may require techni- is the best available method to accurately esti- cal measures mate an individual child’s caloric needs to pro- R The measurement of resting energy expenditure using indirect calorimetry is the best available mote weight gain, loss, or maintenance. The rela- method to accurately estimate a child’s caloric tive and absolute amounts of muscle, fat and bone needs to promote weight gain, loss, or mainte- change during growth [2] , but growth during nance childhood is most commonly assessed by mea- R Dual energy X-ray absorptiometry (DXA)-based suring stature and weight rather than specific tis- bone density measurements are increasingly being used to assess bone health in children with sue compartments. The measurement of body chronic diseases composition provides more detailed information R In addition to anthropometry, the most commonly about nutritional status than the measurement of used clinical method of body composition assess- stature and weight alone. In addition to anthro- ment is DXA Copyright © 2008 S. Karger AG, Basel pometry, the most commonly used clinical method of body composition assessment is dual energy X-ray absorptiometry (DXA). Although mainly used to assess bone health, whole-body DXA Introduction scans also provide measurement of three compartments – bone, fat, and lean body mass. DXA- Accurate nutritional assessment should be an in- based bone density measurements are increas- tegral part of pediatric care. Children at risk of ingly being used to assess bone health in children malnutrition or who are chronically ill should with chronic diseases. Other body composition undergo a detailed nutritional assessment, which methods and bone density measures are mainly sometimes requires technical measures. An im- research tools that are not readily applicable to portant aspect of nutritional assessment is esti- the clinical setting. Table 1. Prediction equations for estimated energy requirements (kcal/day) and physical activity coefficients for healthy children

Infants Prediction equations months 89ؒweight (kg) – 100 + 175 3–0 months 89ؒweight (kg) – 100 + 56 6–3 months 89ؒweight (kg) – 100 + 22 12–6 months 89ؒweight (kg) – 100 + 20 24–12

Males General prediction equation1 Sedentary PA Low active PA Active PA Very active PA coefficient coefficient coefficient coefficient years 88.5–61.9ؒage + PALؒ 1.00 1.13 1.26 1.42 8–3 26.7ؒweight) + 903ؒ(height)) + 20)) years 88.5–61.9ؒage + PALؒ 1.00 1.13 1.26 1.42 18–9 26.7ؒweight) + 903ؒ(height)) + 25)) years 662–9.53ؒage + PALؒ 1.00 1.11 1.25 1.48 18< ((15.91ؒweight) + 539.6ؒ(height)) Overweight 114– 50.9ؒage + PALؒ 1.00 1.12 1.24 1.45 ((years ((19.5ؒweight) + 1,161.4ؒ(height 18–3

Females General prediction equation1 Sedentary PA Low active PA Active PA Very active PA coefficient coefficient coefficient coefficient years 135.3–30.8ؒage + PALؒ 1.00 1.16 1.31 1.56 8–3 10ؒweight) + 934ؒ(height)) + 20)) years 135.3–30.8ؒage + PALؒ 1.00 1.16 1.31 1.56 18–9 10ؒweight) + 934ؒ(height)) + 25)) years 354–6.91ؒage + PALؒ 1.00 1.12 1.27 1.45 18< ((9.36ؒweight) + 726ؒ(height)) Overweight 389–41.2ؒage + PALؒ 1.00 1.18 1.35 1.60 ((years ((15ؒweight) + 701.6ؒ(height 18–3

1 Each prediction equation uses weight (kg) and height (kg), and requires that a physical activity coefficient (PA) be included in the calculation of the estimated energy requirement. The PA categories, based on the physical activity level (PAL, calculated as the ratio of total energy expenditure to resting energy expenditure), are as follows: Sedentary: PAL is estimated to be ≥1.0 and <1.4. Low active: PAL is estimated to be ≥1.4 and <1.6. Active: PAL is estimated to be ≥1.6 and <1.9. Very active: PAL is estimated to be ≥1.9 and <2.5. Adapted from Food and Nutrition Board, Institute of Medicine [5].

Resting Energy Expenditure penditure. REE is used to estimate total ener - gy needs in order to achieve a specific clinical Estimating daily energy needs is particularly im- goal – weight maintenance, loss, or gain. portant in caring for children with varying pedi- Prediction equations based on the child’s age, atric diagnoses that result in undernutrition or sex, weight, and length/height have been devel- obesity. Their energy needs are difficult to esti- oped to estimate REE when direct measurement mate because of variations in metabolic demands is not possible. Unfortunately, these equations, of illness, energy expended in physical activity, derived from measurements of healthy children, and the proportion of the body composed of lean do not perform well for children with serious tissue. REE accounts for 60–70% of total daily ex- health conditions or altered body composition.

18 Pediatric Nutrition in Practice The optimal approach is to measure REE using and regional bone mass and density. DXA-based an indirect calorimeter or metabolic cart that bone mineral density (BMD, g/cm 2 ) measure- measures oxygen consumption and carbon diox- ments are increasingly being used in clinical care ide production. for children at risk of bone disease. Risk factors Accurate REE measurement by indirect calo- for pediatric bone disease include immobility, rimetry requires standardized conditions, such malabsorption, or use of medications known to as early morning testing after a night of restful affect bone health, such as chronic glucocorti- sleep and an 8- to 12-hour (or age- or disease- coid exposure [3] . appropriate) fast. A 40- to 60-min test enables Lumbar spine BMD values should be com- initial environmental adjustment and exclusion pared with reference values for healthy children of measurements during episodes of movement. of the same age and sex, and expressed as a z score 1 During the test, the patient should be in a quiet, or standard deviation (SD) score. A z score of 0 is awake, calm state, in a supine position and not equal to the median value for the reference popu- have performed any physical activity or received lation of children of the same age and sex; a any medications known to change heart rate z score of –1 means the patient’s value is 1 SD be- (such as bronchodilators). Developmentally nor- low that median value for the reference popula- mal children who are at least 5 years of age typ- tion. In clinical practice, BMD z scores from –2 ically do well while watching a movie. Younger to +2 are considered to be in the normal range, children or those with developmental delay of- with a BMD z score of –1 to –2 being a low normal ten require sedation with a short-acting oral value [4] . Based on these findings and the pa- agent. tient’s clinical needs, the practitioner decides Energy needed for growth, physical activity, how best to increase BMD, by optimizing calci- malabsorption, or to support therapeutic growth um and vitamin D in the diet, supplementing acceleration must be added to the REE to esti- with calcium and/or vitamin D, and prescribing mate total energy requirements. Table 1 shows weight-bearing physical activity. the dietary reference intake prediction equations Whole-body DXA scans estimate lean body for estimated energy requirements (kcal/day) and mass, fat mass, and percent body fat in less than physical activity factors for healthy infants and 5 min. DXA body composition assessment is not children. For hospitalized or ill children with less regularly used in the clinical setting, but it may spontaneous physical activity, a factor of 1.3–1.5 prove to be useful in the diagnosis and treat- ! REE is a better estimate of energy needs. Ad- ment of obesity. In cases where it is difficult to ditional corrections are made for disease severity distinguish whether children with high body (such as in children with cystic fibrosis) or mal- mass index have excess adiposity, skinfold as- absorption. In patients who require ‘catch-up’ sessment can be used to make this distinction. growth, additional energy may need to be fac- However, skinfold measurements by less experi- tored into the energy requirement estimation to enced anthropometrists are subject to measure- achieve the desired rate of growth. ment error, and DXA assessments are more accurate. As DXA-based reference data become available for children and cutoff points are es- Dual Energy X-Ray Absorptiometry tablished for the level of body fat associated with the health risks of obesity, DXA could become a DXA is a low energy X-ray (radiation exposure commonly used tool in the diagnosis and treat- less than a day’s background exposure) technique ment of obesity. that measures body composition of the total body,

Use of Technical Measurements in Nutritional Assessment 19 Other Techniques for Assessing Body quantitative computed tomography (pQCT) Composition measures cross-sectional areas for fat and muscle, as well as volumetric bone mineral density of Other research body composition techniques in- cortical and trabecular bone. However, the pQCT clude air displacement plethysmography (Bod is not available for clinical purposes, as there is Pod and Pea Pod) and bioelectrical methods such no pediatric reference database available for in- as total body electrical conductivity (TOBEC) terpretation. and bioelectrical impedance analyzers (BIAs). Bod Pod, Pea Pod and BIAs are currently not used in the clinical care of individual patients C o n c l u s i o n s who have illnesses that influence body composition and hydration. However, these methods are Technical measures in nutritional assessment in used in research settings to describe important the clinical setting: changes in body composition in groups of sub- • Includes indirect calorimetry to directly mea- jects. The TOBEC technology is no longer avail- sure resting energy expenditure. This REE is able except in a few research settings, and is not used to estimate total energy needs in order to available for clinical care. With further research achieve weight maintenance, loss, or gain in experience and the necessary healthy infant and children child reference data, body composition assess- • Includes DXA to measure bone density in ment will likely move into the clinical care set- children at risk of bone disease and body com- ting. position. This may be useful in the diagnosis More advanced imaging technologies, CT and and treatment of obesity MRI, also accurately measure body composition. • Does not include other measures such as Bod However, their risk, availability, and cost do not Pod, TOBEC, BIA, CT, and MRI, as they are make them useful in clinical practice. Peripheral primarily research tools

References

1 Kaplan AS, Zemel BS, et al: Resting 3 Leonard MB, Zemel BS: Current con- 5 Food and Nutrition Board, Institute of energy expenditure in clinical pediat- cepts in pediatric bone disease. Pediatr Medicine: Dietary Reference Intakes

rics: measured versus prediction equa- Clin North Am 2002; 49: 143–173. for Energy, Carbohydrate, Fiber, Fat,

tions. J Pediatr 1995; 127: 200–205. 4 Zemel B, Petit M: Evaluation; in Sawyer Fatty Acids, Cholesterol, Protein, and 2 Zemel BS: Body composition during AJ, Bachrach LK, Fung EB (eds): Bone Amino Acids (Macronutrients). Wash- growth and development; in Cameron Densitometry in Growing Patients. ington, National Academies Press, N (ed): Human Growth and Develop- Totowa, Humana Press, 2007, pp 115– 2002. ment. Amsterdam, Academic Press, 126. 2002, pp 271–294.

20 Pediatric Nutrition in Practice Koletzko B. (ed): Pediatric Nutrition in Practice. Basel, Karger, 2008, pp 21–26

1 General Aspects of Childhood Nutrition

1.2 Nutritional Assessment

1.2.4 Use of Laboratory Measurements in Nutritional Assessment

Ryan Himes ؒ Robert Shulman 1

Key Words ple deficiencies are frequently encountered, a ju- Protein ؒ Vitamin ؒ Laboratory test ؒ Malabsorption dicious approach to ordering laboratory tests is recommended. While a rather comprehensive list of laboratory tests is presented here, clinical suspicion should guide the selection of specific in- Key Messages vestigations. Depending on the clinical labora- R Identification and prevention of malnutrition is crucial in the ill child tory facilities, turnaround time on certain tests R An understanding of the relationship between may preclude their usefulness in the acute set- measures of visceral protein status and inflamma- ting. Familiarity with these limitations will help tory responses, and changes in fluid status is the to avoid ordering tests that do not contribute key to avoid their misinterpretation meaningfully to the management of the child. R The approach to evaluating vitamin deficiency is Table 1 provides a summary of the laboratory determined by the knowledge of predisposing conditions Copyright © 2008 S. Karger AG, Basel tests discussed here including their normal values, signs and symptoms of the deficiency state, and pitfalls to avoid in their interpretation.

Introduction P r o t e i n

Laboratory tests may aid in the diagnosis of pri- Assessment of visceral protein stores is common- mary childhood malnutrition (resulting from in- ly made by measuring serum proteins (table 2), adequate intake) and are invaluable in guiding most commonly albumin, prealbumin (trans- therapeutic decisions in secondary malnutrition thyretin) and retinol-binding protein. Interpre- (resulting from conditions of increased need for tation of serum total protein is predicated on nor- or losses of substrate). Because nutritional status mal globulin levels, limiting its clinical useful- is an independent predictor of outcome in the ness. Generally, serial measurements of protein sick child, strict attention to indicators of viscer- status are more meaningful than single values al protein stores and vitamin or mineral deficien- and an understanding of their biological half- cy is imperative. lives will dictate the frequency of assessment (ta- Although signs and symptoms of specific nu- ble 2 ). A framework for the investigation of hypo- trient deficiencies commonly overlap and multi- albuminemia is shown in figure 1. Table 1. Frequently used laboratory tests in the assessment of childhood nutrition

Test Normal Range1 Function/Description Deficiency Pitfalls to Avoid (specimen)

Albumin Infants: 29–55 g/l Most abundant serum protein, Negative acute-phase reactant (serum) Children: 37–55 g/l [2] half-life 20 days f with hepatic synthetic dysfunction Changes with hydration status and fluid shifts Alkaline Infants: 150–420 U/l Zinc-dependent metallo-enzyme Low alkaline phosphatase phosphatase 2–10 years: 100–320 U/l found in liver, bone, biliary warrants consideration of zinc (serum) Adolescent boys: 100–390 U/l epithelium, kidney and intestine deficiency Adolescent girls: 100–320 U/l Adults: 30–120 U/l

␣1-Antitrypsin <6 months: <4.5 mg/g stool Measure of protein loss from the Unstable at pH <3, may be (stool) >6 months: <3 mg/g stool [3] gut unsuitable to assess gastric protein loss [4] Biotin 214–246 pmol/l [5] Water-soluble vitamin, cofactor Dermatitis, glossitis, alopecia, Anticonvulsants, hemodialysis and (serum) for carboxylases poor growth, ataxia, weakness, parenteral nutrition may give rise depression and seizures to deficiency Calcium Preterm: 1.6–2.8 mmol/l Skeletal integrity, cofactor in Fatigue, muscular irritability, Factitious hypocalcemia caused by (serum) Term to 10 days: 1.9–2.6 mmol/l clotting cascade and tetany and seizures low albumin (50% is bound to 10 days to 2 years: 2.3–2.8 mmol/l neuromuscular function albumin) 2–12 years: 2.2–2.7 mmol/l Adults: 2.2–2.5 mmol/l Ceruloplasmin Birth to 3 months: 40–160 mg/l Carries 90% of serum copper Positive acute-phase reactant (serum) 3–12 months: 290–380 mg/l 1–15 years: 230–490 mg/l [3] Copper Birth to 6 months: 3.1–4.2 μmol/l Mineral cofactor for superoxide Anemia, neutropenia, Supra-physiologic doses of iron or (serum) 6 years: 14.1–29.8 μmol/l dismutase and enzymes of depigmentation, zinc may impair absorption of 12 years: 12.6–25.1 μmol/l connective tissue synthesis characteristic hair changes, copper [5] Adults (M): 11–37.7 μmol/l weakened bone and connective Adults (F): 12.6–24.3 μmol/l tissue [5] Creatinine Neonates: 26.5–88.4 μmol/l Product of muscle creatinine- Diminished glomerular filtration (serum) Infants: 17.7–35.4 μmol/l phosphate metabolism, level rate, cimetidine, cephalosporins Children: 26.5–61.9 μmol/l parallels muscle mass and trimethoprim may increase Adolescents: 44.2–88.4 μmol/l serum creatinine [6] Adults (M): 61.9–114.9 μmol/l Adults (F): 53–97.2 μmol/l Elastase >200 μg/g stool Indicator of exocrine pancreas (stool) sufficiency Fat <3 years: >85%* Indicator of fat malabsorption Classically, a 72-hour stool (stool) >3 years: >95%* [7] collection with dietary diary *Expressed as coefficient of absorption Ferritin Neonates: 25–200 μg/l Major storage form of iron, levels Positive acute-phase reactant (serum) 1 month: 200–600 μg/l mirror body reserves 2–5 months: 50–200 μg/l Early and sensitive indicator of 6 months to 15 years: 7–140 μg/l iron-deficiency anemia Adults: 10–250 μg/l

22 Pediatric Nutrition in Practice Test Normal Range1 Function/Description Deficiency Pitfalls to Avoid (specimen)

Folate Neonates: 11–147 nmol/l Water-soluble vitamin, role in Macrocytic anemia, Deficiency may be clinically indis- (serum) Infants: 34–125 nmol/l DNA/RNA synthesis and amino hypersegmented tinguishable from that of B12 2–16 years: 11–48 nmol/l acid metabolism neutrophils, glossitis, stomatitis, except the neurological signs of >16 years: 7–45 nmol/l poor growth and fetal neural the latter tube defects Methotrexate, phenytoin and sulfasalazine antagonize folate utilization Hemoglobin 0–8 days: 2.06–3.79 mmol/l Oxygen-carrying moiety in red Microcytic Influenced by hydration status, (whole blood) 9 days: 1.66–3.33 mmol/l blood cell Iron deficiency, chronic disease nutrition, pregnancy 3 months: 1.53–2.25 mmol/l Normocytic 1 year: 1.38–2.14 mmol/l Chronic disease, acute bleeding 1 3 years: 1.58–2.31 mmol/l Macrocytic 11 years: 1.72–2.43 mmol/l B12, folate deficiency Adults (M): 1.86–2.48 mmol/l Adults (F): 2.17–2.79 mmol/l [3] Iron Neonates: 17.9–44.8 μmol/l Component in heme and Microcytic anemia, pallor, Transferrin is a sensitive measure (serum) Infants: 7.2–17.9 μmol/l cytochrome proteins weakness, dyspnea of body iron stores, however, it is a Children: 9–21.5 μmol/l negative acute-phase protein Adults (M): 11.6–31.3 μmol/l Adults (F): 9–30.4 μmol/l Lymphocytes >1,500/mm3 Total lymphocyte count is (whole blood) correlated to degree of malnutrition [6] Magnesium 0.65–1 mmol/l Important for neuromuscular Arrhythmia, tetany, f by low serum albumin (serum) conduction; enzyme cofactor hypocalcemia, hypokalemia d by hemolyzed specimens pH >5.5 Low fecal pH usually implies Improper specimen processing (stool) carbohydrate malabsorption may lead to false values Phosphorus Neonates: 1.45–2.91 mmol/l Vital for energy transfer at Confusion, respiratory distress, ‘refeeding syndrome’ is (serum) 10 days to 2 years: 1.45–2.16 mmol/l cellular level tissue hypoxia, bone hypophosphatemia and 2–12 years: 1.45–1.78 mmol/l abnormalities and d alkaline hypokalemia complicating >12 years: 0.87–1.45 mmol/l phosphatase nutritional rehabilitation of the severely malnourished patient Prealbumin Neonates: 70–390 mg/l Gauge of visceral protein stores, Negative acute-phase reactant (serum) 1–6 months: 80–340 mg/l half-life of 2 days 6 months to 4 years: 20–360 mg/l 4–6 years: 120–300 mg/l 6–19 years: 120–420 mg/l Prothrombin 10.5–15.5 s Used to assess vitamin K Also prolonged in liver dysfunction, time sufficiency malabsorption syndromes, (plasma) prolonged antibiotic use and warfarin therapy Reducing Negative Presence suggests carbohydrate Improper specimen processing substances malabsorption may lead to falsely normal values (stool) Retinol-binding <9 years: 10–7.80 mg/l Gauge of visceral protein stores, Negative acute-phase reactant protein >9 years: 13–99 mg/l [2] half-life of 12 h f in vitamin A deficiency, hepatic (serum) dysfunction d in renal failure

Use of Laboratory Measurements in Nutritional Assessment 23 Table 1 (continued)

Test Normal Range1 Function/Description Deficiency Pitfalls to Avoid (specimen)

Selenium Preterm: 0.6–1 μmol/l Water-soluble vitamin essential Cardiomyopathy (Keshan (serum) Term: 0.8–1.1 μmol/l for glutathione peroxidase disease), myositis and nail 1–5 years: 1.4–1.7 μmol/l dystrophy 6–9 years: 1.4–1.8 μmol/l >10 years: 1.6–2.1 μmol/l [5] Urea Preterm (1st week): 1.1–8.9 mmol/l Produced in liver from protein f in low protein intake states nitrogen Neonates: 1.4–4.3 mmol/l degradation and is renally d in high protein diets but also (serum) Infants/children: 1.8–6.4 mmol/l excreted kidney disease Adults: 2.1–7.1 mmol/l Vitamin A Preterm: 0.45–1.6 μmol/l Fat-soluble vitamin that Reversible night blindness f in liver disease, zinc deficiency (serum) Term: 0.63–1.7 μmol/l functions in vision, maintenance (the 1st clinical manifestation) [5] 1–6 years: 0.7–1.5 μmol/l of epithelial tissue and that, uncorrected, is progressive d with oral contraceptive pill use 7–12 years: 0.7–1.7 μmol/l immunity, 90% stored in liver to corneal scarring 13–19 years: 0.91–2.5 μmol/l

Vitamin B1 Measure RBC transketolase activity Water-soluble vitamin with role Beriberi: cardiac failure, (thiamine, <15% in oxidative phosphorylation and peripheral neuropathy, 8 edema whole pentose phosphate pathway Wernicke encephalopathy, blood) Korsakoff syndrome

Vitamin B2 Measure RBC glutathione reductase Water-soluble vitamin that Dermatitis, cheilitis, glossitis and (riboflavin, activity facilitates red/ox reactions visual impairment whole blood) >1.2 activity coefficients

Vitamin B6 Measure pyridoxal 5‘-phosphate Cofactor for enzymes in Microcytic, hypochromic anemia, f level with isoniazid treatment (pyridoxine, concentration aminotransferase reactions dermatitis, cheilosis, stomatitis, plasma) 14.6–72.8 nmol/l [3] including δ-aminolevulinic acid peripheral neuropathy, seizures, and the manufacture of f AST and ALT serotonin [5]

Vitamin B12 Neonates: 118–959 pmol/l Water-soluble vitamin active in Megaloblastic anemia, f by phenytoin, proton-pump (cobalamin, Infants/children: 147–616 pmol/l DNA synthesis and branched- hypersegmented neutrophils and inhibitors, neomycin and folate serum) chain amino acid metabolism glossitis, stomatitis, weakness, deficiency elevated homocysteine and methylmalonic acid Vitamin C 22.7–85.2 μmol/l Water-soluble antioxidant Scurvy: petechial and gingival (ascorbate, vitamin important in collagen hemorrhage, gingivitis and poor plasma) synthesis wound healing Vitamin D Summer: 15–80 μg/l Fat-soluble vitamin involved in Deficiency primarily affects bone f with anticonvulsant therapy and (25-hydroxyl, Winter: 14–42 μg/l [3] calcium and phosphate and is called rickets; cholestyramine plasma) homeostasis f serum calcium, phosphate and d alkaline phosphatase Vitamin E <11 years: 7–35 μmol/l Fat-soluble antioxidant that Diminished deep tendon reflexes, Carried in serum bound to lipid, (serum) >11 years: 12–46 μmol/l protects cell membranes impaired balance and gait therefore, hyperlipidemia may mask deficiency Vitamin E:lipid ratio useful in these circumstances Zinc 10.7–18.4 μmol/l Cofactor for >200 enzymes, Acrodermatitis enteropathica, d in hemolyzed specimens (plasma) notably alkaline phosphatase, also delayed wound healing, f in sickle cell patients, RNA/DNA polymerase and impaired taste, growth failure, hypoalbuminemia superoxide dismutase [5] delayed puberty and diarrhea

1 All reference ranges from the Harriet Lane Handbook [1], unless otherwise noted.

24 Pediatric Nutrition in Practice Low serum albumin

? Intake ? Factitious ? Losses

Diet history Assess volume status Urine (urinalysis) • Food security Consider inflammatory state Gastrointestinal ␣ • Formula preparation (stool ( 1)-antitrypsin) • Restrictive diets Burns 1 Fig. 1. A suggested framework for investigating hypoalbuminemia in children.

The most important limitation to measure- Table 2. Serum proteins in the assessment of visceral ment of serum proteins is their function in the protein stores acute phase response ( table 3). Appreciating the Protein Half-life positive and negative acute phase reactants will help avoid misinterpretation of data. Another Albumin 20 days limitation of measuring serum proteins is that Prealbumin (transthyretin) 2 days their manufacture is tied to hepatic synthetic Retinol-binding protein 12 h function. Therefore, in the child with advanced liver disease a low serum protein may not necessarily reflect a lack of substrate but rather a lack of synthetic function. Finally, their concentra- Table 3. Serum proteins used in the acute-phase response tions are also susceptible to changes in hydration status and fluid shifts, and these changes may oc- Positive acute-phase Negative acute-phase cur rapidly (e.g., increased vascular permeability reactants reactants associated with sepsis or trauma). ␣1-Antitrypsin Albumin C3 complement Prealbumin (transthyretin) C-reactive protein Retinol-binding protein Vitamins and Minerals Ferritin Transferrin Fibrinogen Thyroxin-binding globulin Evaluating vitamin and mineral stores should take into account suspected underlying pathology (e.g., measurement of fat-soluble vitamins in conditions associated with fat malabsorption An often overlooked class of patients prone to such as celiac disease or cystic fibrosis). Frequent- malnutrition are those with absent (surgically rely, signs and symptoms of nutrient deficiency sected) or diseased (Crohn’s disease, small bowel overlap with one another underscoring the im- bacterial overgrowth) terminal ilea. Deficiencies portance of an informed approach to laboratory of vitamins B 12 and K and zinc are prevalent in investigation. these patients.

Use of Laboratory Measurements in Nutritional Assessment 25 Finally, the effects of drugs, particularly ther- on the most liquid portion of the stool and can apeutic agents, are important considerations. An be done at the bedside using Clinitest h strips. exhaustive list of these interactions is beyond the Hydrogen breath testing is a sensitive method scope of this text, however, some important nu- of detecting carbohydrate malabsorption. Breath trient-specific examples are shown in table 1 . hydrogen is measured at baseline and after the patient is given an oral load of the carbohydrate of interest (e.g. lactose): a rise in hydrogen 110 T e s t s o f M a l a b s o r p t i o n ppm above baseline is diagnostic. False-negative tests may be obtained in patients recently admin- Analysis of the stool is a logical starting point for istered antibiotics. Additionally, a positive test the investigation of malabsorption. does not always correlate with symptoms of intol- (1) Enteric protein loss: Stool a 1 -antitrypsin, un- erance. like albumin, passes into the stool undegrad- Small bowel bacterial overgrowth may be as- ed. sessed in an analogous manner using lactulose or (2) Fat malabsorption: Fecal fat as assessed by 72- glucose. A peak within 15–30 min or elevated hour collection with diet record is an accurate, baseline breath hydrogen ( 1 40 ppm) is indicative albeit cumbersome tool (for patients and labo- of bacterial overgrowth. ratory technicians) to document malabsorption. A fecal smear with Sudan staining gives a rough qualitative estimate of steatorrhea and C o n c l u s i o n s may be useful for screening purposes. Fecal elastase is a specific gauge of exocrine pancre- • Serial measurement of visceral protein status as sufficiency. Its level is not affected by pan- helps guide nutritional therapy creatic enzyme supplementation. • Evaluation of hypoalbuminemia must take (3) Carbohydrate malabsorption: Fecal pH and into account potential deficient intake, poten- reducing substances are indicators of unab- tial losses, the inflammatory response (acute sorbed carbohydrate. Testing should be done phase) and the volume status of the patient

References

1 Gunn V, Nechyba C (ed): The Harriet 4 Walker A, Goulet O, Kleinman R, et al 6 Ravel R: Clinical Laboratory Medicine, Lane Handbook, ed 16. Philadelphia, (eds): Pediatric Gastrointestinal Dis- ed 6. St. Louis, Mosby, 1995, p 655, Mosby, 2002, pp 549–556. ease, ed 4. Hamilton, BC Decker, 2004, p 433. 2 Kleinman R (ed): AAP Pediatric Nutri- p 195. 7 Guandalini S: Essential Pediatric Gas- tion Handbook, ed 5. Elk Grove Village, 5 Sauberlich H: Laboratory Tests for the troenterology, Hepatology, and Nutri- AAP, 2004, pp 407–423. Assessment of Nutritional Status, ed 2. tion. New York, McGraw-Hill, 2005, 3 Benedict A, Gilger M, Klish W, et al: Boca Raton, CRC Press, 1998. p 133. The Baylor Pediatric Nutrition Hand- book, ed 4. Houston, Baylor College of Medicine, 2004, pp 34–43.

26 Pediatric Nutrition in Practice Koletzko B. (ed): Pediatric Nutrition in Practice. Basel, Karger, 2008, pp 27–30

1 General Aspects of Childhood Nutrition

1.3 Nutritional Needs

1.3.1 Nutrient Intake Values: Concepts and Applications Berthold Koletzko

Key Words based dietary guidelines; they serve as the basis for national or regional nutrition policies, nutri- ؒ Nutrient requirements ؒ Recommended intakes Dietary requirements ؒ Recommended dietary tional education programs, food regulations and allowances ؒ Extrapolation provide reference points for the labeling of food products if nutrient contents are expressed as a percentage of an NIV [1] . The term NIV has been Key Messages agreed upon by a recent expert consultation con- R Nutrient intake values (NIV) provide estimates on vened by the United Nations University’s Food appropriate dietary substrate supply for popula- and Nutrition Programme, in collaboration with tions of healthy people the Food and Agriculture Organization (FAO), R The average nutrient requirement is the estimated median requirement for a particular age- and sex- the World Health Organization (WHO), and specific group UNICEF [2] , rather than the terms nutrient refer- R The population reference intake is the intake meet- ence values (NRV) previously used in Australia ing the known nutrient needs of practically all and New Zealand, reference values for nutrient healthy individuals in a particular population supply in Germany/Austria/Switzerland, dietary R Major uncertainties exist in the establishment of reference values in the United Kingdom, and di- NIV for infants, children and adolescents due to limited scientific data. Deriving NIV from observed etary reference intakes or previously recom- nutrient intakes (e.g. the supply with breast milk) mended dietary allowances by the United States or extrapolation from other age groups has consid- and Canada [2] . Conceptually NIV are based on erable limitations physiological requirements, which are defined as Copyright © 2008 S. Karger AG, Basel the amounts and chemical forms of nutrients needed systematically to maintain normal health and development, without disturbance of the me- Introduction tabolism of any other nutrient and without extreme homeostatic processes and excessive deple- Nutrient intake values (NIV) comprise a set of tion or surplus in bodily depots [1] . The dietary recommendations on dietary substrate supply for requirement of a nutrient is the intake sufficient populations of healthy people. NIV are used to to meet the physiological requirement, consider- assess intake data from dietary surveys and food ing nutrient bioavailability from foodstuffs. NIV statistics, to provide guidance on appropriate di- reflect the estimated distributions of nutrient in- etary composition, meal provision, and food- takes required to achieve a specific outcome in a defined population considered healthy, but for for nutrient labeling of foods, with the exception many nutrients this distribution of requirements of energy where the average nutrient requirement and the modifying biological and environmental is used because the provision of energy equivalent factors are not well known, which results in con- to the PRI would result in overfeeding and induc- siderable uncertainty in NIV. Therefore, NIV tion of obesity in about one half of the population. should be considered approximations that reflect The upper nutrient level (UNL; or upper tolerable the often limited data available. NIV are even intake level) is the highest level of daily nutrient more uncertain for infants and young children intake that is likely to pose no risk of adverse where original data are particularly scarce, and health effects for almost all individuals of a par- hence NIV are often derived from interpolation ticular age- and sex-specific group. Ideally, the of data from other age groups which must be ex- UNL is based on an analysis of the statistical dis- pected to yield inaccurate values. It is important tribution of risk for high nutrient intakes. The to remember NIV refer to populations, but not to UNL is generally set at a level where the risk of individuals. NIV do not allow determination of excessive intakes is practically nonexistent. A nu- an insufficient nutrient intake or a nutrient defi- trient intake equal to or higher than the UNL ciency in an individual, or accurate determina- should be avoided on a chronic basis. tion of nutrient needs in disease states. Examples of NIV for children and adolescents are provided in Annex 4.2.

Definitions of NIV Limitations in the Estimation of NIV NIV for populations are generally estimated based on the concept that individual requirements fol- The concept of a near normal, symmetrical dis- low a statistical distribution (bell-shaped curve; tribution of nutrient requirements ( fig. 1 ) is fig. 1). The average nutrient requirement (ANR; known not to be correct for a number of nutri- also called estimated average requirement [EAR]) ents. Examples are the nutrient needs for iron, vi- is the estimated average of median requirement of tamin D and polyunsaturated fatty acids. Iron re- a specific nutrient in the population derived from quirements are not normally distributed, with a statistical distribution of requirement criterion higher needs in menstruating women, particu- and for a particular age- and sex-specific group larly in those with large blood losses. Vitamin D based on a specific biological endpoint or bio- requirements depend on endogenous synthesis in chemical measure. The population reference in- the skin and hence on variation of UV light expo- take (PRI; also called individual nutrient level sure with geographic location and time of the 97% [INL 97 ], reference nutrient intake [RNI], or year, but also on biological determinants such as recommended dietary allowance [RDA]) is the degree of skin pigmentation and genetic varia- nutrient intake considered adequate to meet the tions in vitamin D receptor. The dietary needs of known nutrient needs of practically all healthy essential fatty acids vary considerably with ge- individuals in a particular age- and sex-specific netic polymorphisms for the fatty acid desatura- group. Based on the assumed statistical distribution enzymes ⌬ 6 - and ⌬ 5 -desaturases that deter- tion of requirements, the PRI is set at a level of mine the relative turnover of polyunsaturated intake that meets the needs of 97% of the popula- fatty acids [3] . tion (mean + 2 SD; fig. 1). The PRI value is gener- The establishment of NIV for infants, children ally used as the target for provision of essential and adolescents is further hampered by severe nutrients to populations and as the reference point limitations in the available scientific data ob-

28 Pediatric Nutrition in Practice Average nutrient requirement (ANR) estimated median of distribution

Population reference intake (PRI) ~~97.5th percentile or mean + 1.96 SD Upper nutrient level (UNL) highest level of daily nutrient intake that poses no risk Frequency 1

Increasing nutrient intake

Fig. 1. Conceptual basis for nutrient intake values.

tained in healthy children [4] . This is unfortunate and the subsequent risk of hypertension, obesity, because infants, children and adolescents have diabetes mellitus, and cardiovascular disease in relatively large nutrient needs due to their growth adult life [6] . and development, and adequate substrate is of ut- The derivation of NIV from observed intakes most importance to support their short- and long- is a standard approach for infants during the first term health, wellbeing, and performance [5] . Cur- 6 months of life, when the intakes of breastfed ba- rent reference values for nutrient intakes vary bies are considered an appropriate guide to opti- considerably (see Annex 4.2), partly due the limi- mal nutritional supply. However, this approach tations of the available scientific database and has major limitations because the actual metabo- partly due to major differences in underlying con- lizable substrate intakes of breastfed infants have cepts, definitions, and terminology [4] . not been well determined. The volume of milk Due to the lack of adequate scientific studies, consumed varies between about 550 and 1,100 ml/ NIV for children are often based on observed nu- day, and milk composition differs between wom- trient intakes of groups of children in apparent en and changes during the course of lactation, good health. However, this approach is weak, be- during the day and even during a single feeding cause it assumes that the children in these sur- [1] . Moreover, the bioavailability of substrates and veys are in good health and are achieving their their metabolism differs between infants fed hu- full genetic potential and that their diets are man milk and those fed infant formula and com- quantitatively and qualitatively appropriate and plementary feeds, which can result in differences free from adverse long-term effects [1] . The con- in requirements. Therefore, human milk compo- cerns with respect to this approach are strength- sition and the nutrient supply to breastfed infants ened by recent evidence on the long-term effects may not always provide useful guidance for in- of early nutrition on metabolic programming fants that are not exclusively breastfed.

Nutrient Intake Values: Concepts and Applications 29 Due to the paucity of original research data for • Population reference intakes (PRI; also refer- estimating nutrient requirements in the pediatric ence nutrient intakes [RNI], or recommended age group, very often NIV are extrapolated from dietary allowances [RDA]) are the levels of in- data for other age groups. Frequently, this intake that meet the needs of almost all healthy volves extrapolation from adults to children and individuals of a given age and sex group adolescents. Examples of extrapolation methods • The diet for healthy children should generally that are used include body size (weight or meta- provide nutrient intakes matching the PRI, bolic weight), energy intakes for age, or factorial except for energy where average nutrient re- estimates of requirements for growth [4] . How- quirements provide guidance on appropriate ever, there is no truly correct method for extrapo- intakes for groups lation that would result in physiologically ade- • Children affected by disease, malnutrition or quate NIV for infants, children and adolescents. those in whom catch-up growth is desired It is important that the rationale or scientific ba- may have nutrient needs that differ markedly sis for the method chosen should be completely from PRI transparent and thoroughly described for each nutrient and life-stage group. Extrapolation is always the second choice, and the use of innova- Acknowledgment tive, noninvasive methods or of existing methods (e.g., stable isotopes) is encouraged to determine The author’s work in this area is carried out with partial financial support from the Commission of the European nutrient requirements of infants, children, and Communities specific RTD Program, ‘Food Quality and adolescents [4] . Safety – Integrating and Strengthening the European Research Area’, within the 6th Framework Program, research contract No. FP6-036196-2 (Aligning nutrient recommendations across Europe with special focus on Conclusions vulnerable groups and consumer understanding). This paper does not necessarily reflect the views of the Com- • Nutrient intake values (NIV) provide an esti- mission and in no way anticipates future policy in this mate for adequate nutrient provision to popula- area. tions considered healthy, but do not determine the optimal nutrient supply for an individual

References

1 Aggett P, Bresson J, Haschke F, Hernell 2 King JC, Garza C: International harmo- 4 Atkinson SA, Koletzko B: Determining O, Koletzko B, Lafeber H, Michaelsen nization of approaches for developing life-stage groups and extrapolating KF, Micheli J, Ormisson A, Rey J, Sala- nutrient-based dietary standards: ex- nutrient intake values (NIVs). Food

zar de Sousa J, Weaver L: Recommend- ecutive summary. Food Nutr Bull 2007; Nutr Bull 2007; 28:S61–S76. ed dietary allowances (RDAs), recom- 28:S3–S12. 5 Koletzko B, Aggett PJ, Bindels JG, Bung mended dietary intakes (RDIs), 3 Schaeffer L, Gohlke H, Müller M, Heid P, Ferre P, Gil A, Lentze MJ, Roberfroid recommended nutrient intakes (RNIs), IM, Palmer LJ, Kompauer I, Demmel- M, Strobel S: Growth, development and and population reference intakes (PRIs) mair H, Illig T, Koletzko B, Heinrich J: differentiation: a functional food sci-

are not ‘recommended intakes’. J Pedi- Common genetic variants of the FADS1 ence approach. Br J Nutr 1998; 80(suppl

atr Gastroenterol Nutr 1997; 25: 236– FADS2 gene cluster and their recon- 1):S5–S45. 241. structed haplotypes are associated with 6 Koletzko B, Akerblom H, Dodds PF, the fatty acid composition in phospho- Ashwell M (eds): Early nutrition and its

lipids. Hum Mol Genet 2006; 15: 1745– later consequences: new opportunities.

1756. Adv Exp Med Biol 2005; 569: 1–237.

30 Pediatric Nutrition in Practice Koletzko B. (ed): Pediatric Nutrition in Practice. Basel, Karger, 2008, pp 31–36

1 General Aspects of Childhood Nutrition

1.3 Nutritional Needs

1.3.2 Energy Requirements of Infants, Children and Adolescents Nancy Butte

Key Words the requirements of practically all individuals in -Energy needs, requirements ؒ Basal metabolic the population, recommendations for energy in rate ؒ Physical activity level ؒ Energy cost of take are based on the average requirement of the growth population to avoid energy intakes that exceed requirements. Recommendations for energy intake and physical activity are intended to support Key Messages and maintain the growth and development of R Energy requirements of infants, children and ado- well-nourished and healthy infants, children and lescents are defined as the amount of energy need- adolescents. The 2004 FAO/WHO/UNU recom- ed to balance total energy expenditure at a desir- mendations for energy intake are based upon es- able level of physical activity, and to support optimal growth and development consistent with timates of TEE and an allowance for growth [1] . long-term health For infants, TEE is predicted from measurements R Recommendations for energy intake are based on of TEE by the stable isotope method, doubly la- the average requirement of the population to beled water (DLW). For children and adolescents, avoid energy intakes that exceed the require- heart rate monitoring and the DLW method were ments R Recommendations for energy intake to support a used to predict TEE. The energy cost of growth moderately active lifestyle are encouraged to was derived from average velocities and the com- maintain fitness and health and to reduce the risk position of weight gain. of overnutrition Copyright © 2008 S. Karger AG, Basel Energy requirements during growth and development can be partitioned into components of basal metabolism, thermogenesis, physical activity, and energy cost of growth [2] . Basal metabo- Introduction lism is defined as that energy expended to maintain cellular and tissue processes fundamental to The energy requirements of infants, children and the organism. The Schofield equations [3] to pre- adolescents are defined as the amount of energy dict basal metabolic rate (BMR) are presented in needed to balance total energy expenditure (TEE) table 1. The thermic effect of feeding (TEF) refers at a desirable level of physical activity, and to sup- to the energy required for the ingestion and di- port optimal growth and development consistent gestion of food and for the absorption, transport with long-term health [1]. Unlike recommenda- and utilization of nutrients. TEF amounts to tions for other nutrients which meet or exceed about 10% of the daily energy expenditure. Ther- Table 1. Schofield equations for estimating basal metabolic rate (BMR) from weight (kg) in children [3]

Under 3 years Males BMR (MJ/day) = 0.249 weight – 0.127 SEE = 0.293 Females BMR (MJ/day) = 0.244 weight – 0.130 SEE = 0.246 Males BMR (kcal/day) = 59.5 weight – 30.4 SEE = 70 Females BMR (kcal/day) = 58.3 weight – 31.1 SEE = 59 3–10 years Males BMR (MJ/day) = 0.095 weight = 2.110 SEE = 0.280 Females BMR (MJ/day) = 0.085 weight = 2.033 SEE = 0.292 Males BMR (kcal/day) = 22.7 weight = 504.3 SEE = 67 Females BMR (kcal/day) = 20.3 weight = 485.9 SEE = 70 10–18 years Males BMR (MJ/day) = 0.074 weight = 2.754 SEE= 0.440 Females BMR (MJ/day) = 0.056 weight = 2.898 SEE = 0.466 Males BMR (kcal/day) = 17.7 weight = 658.2 SEE = 105 Females BMR (kcal/day) = 13.4 weight = 692.6 SEE = 111

SEE = Standard error of estimation.

moregulation can constitute an additional ener- Energy Requirements of Infants gy cost when exposed to temperatures below and above thermoneutrality, however, clothing and In the recent FAO/WHO/UNU recommendations behavior usually counteract such environmental [1] , the average energy requirements of infants influences. Physical activity is the most variable were based upon the TEE and growth rates of component of energy requirements, and entails healthy, well-nourished infants (table 2; figs. 1, 2). both obligatory and discretionary physical activ- In the FAO/WHO/UNU report, the median ities. The energy cost of growth as a percentage of weight-for-age and monthly rates of weight gain of total energy requirements decreases from around the WHO pooled breastfed data set were used to 35% at 1 month to 3% at 12 months of age, and calculate energy requirements [6] . A prediction remains low until the pubertal growth spurt, at equation (eq. 1) for TEE was developed based on which time it increases to about 4% [2] . longitudinal data on 76 healthy infants studied at 3-month intervals for the first 2 years of life [2, 7] .

Approaches to Estimating Energy TEE (MJ/day) = –0.416 + 0.371 weight (kg) SEE = 0.456 (eq. 1) Requirements TEE (kcal/day) = –99.4 + 88.6 weight (kg) SEE = 109, Energy requirements are derived from TEE based on the factorial approach or measurements using in which SEE is the standard error of estimation. the DLW method or heart rate monitoring. DLW Assuming energy equivalents of protein (23.6 is a stable (nonradioactive) isotope method that kJ/g or 5.65 kcal/g) and fat (38.7 kJ/g or 9.25 kcal/ provides an estimate of TEE in free-living indi- g), and body composition changes during infan- viduals [4] . In the heart rate method, TEE is pre- cy [8, 9] , energy deposition decreases substantial- dicted from heart rate based on the nearly linear ly during the first year of life from approximately relationship between heart rate and oxygen con- 730 kJ/day (175 kcal/day) at 0–3 months, to 250 sumption during submaximal muscular work kJ/day (60 kcal/day) at 4–6 months and 85 kJ/day [5] . (20 kcal/day) for 1–12 months of age.

32 Pediatric Nutrition in Practice Table 2. Energy requirements of boys during the first Table 3. Energy requirements of girls during the first year of life year of life

Age 1985 FAO/WHO/ 2004 FAO/WHO/ Age 1985 FAO/WHO/ 2004 FAO/WHO/ months UNU [15] UNU [1] months UNU [15] UNU [1] kJ/kg/ MJ/day kcal/ kJ/kg/ kcal/kg/ kJ/kg/ MJ/ kcal/ kJ/kg/ kcal/kg/ day day day day day day day day day

0–1 519 2.166 518 473 113 0–1 519 1.942 464 447 107 1–2 485 2.387 570 434 104 1–2 485 2.162 517 421 101 2–3 456 2.494 596 397 95 2–3 456 2.301 550 395 94 3–4 431 2.38 569 343 82 3–4 431 2.245 537 350 84 4–5 414 2.546 608 340 81 4–5 414 2.389 571 345 83 5–6 404 2.674 639 337 81 5–6 404 2.507 599 341 82 1 6–7 397 2.73 653 329 79 6–7 397 2.525 604 328 78 7–8 395 2.845 680 330 79 7–8 395 2.63 629 328 78 8–9 397 2.936 702 330 79 8–9 397 2.728 652 328 78 9–10 414 3.058 731 335 80 9–10 414 2.828 676 331 79 10–11 418 3.145 752 336 80 10–11 418 2.902 694 331 79 11–12 437 3.243 775 337 81 11–12 437 2.981 712 331 79

Table 4. Energy requirements of boys at 0–18 years of Table 5. Energy requirements of girls at 0–18 years of age, computed for a moderate level of physical activity age, computed for a moderate level of physical activity

Age 1985 FAO/WHO/ 2004 FAO/WHO/UNU [1] Age 1985 FAO/WHO/ 2004 FAO/WHO/UNU [1] years UNU [15] years UNU [15] kJ/kg/ MJ/ kcal/ kJ/kg/ kcal/kg/ kJ/kg/ MJ/ kcal/ kJ/kg/ kcal/kg/ day day day day day day day day day day

1–2 439 4.0 950 345 82 1–2 439 3.6 850 335 80 2–3 418 4.7 1,125 350 84 2–3 418 4.4 1,050 339 81 3–4 397 5.2 1,250 334 80 3–4 397 4.8 1,150 322 77 4–5 397 5.7 1,350 322 77 4–5 397 5.2 1,250 310 74 5–6 377 6.1 1,475 312 74 5–6 356 5.6 1,325 301 72 6–7 377 6.6 1,575 303 73 6–7 356 6.0 1,425 289 69 7–8 326 7.1 1,700 295 71 7–8 280 6.5 1,550 280 67 8–9 326 7.7 1,825 287 69 8–9 280 7.1 1,700 268 64 9–10 326 8.3 1,975 279 67 9–10 280 7.7 1,850 255 61 10–11 267 9.0 2,150 270 65 10–11 227 8.4 2,000 243 58 11–12 267 9.8 2,350 261 62 11–12 227 9.0 2,150 230 55 12–13 228 10.7 2,550 252 60 12–13 189 9.5 2,275 218 52 13–14 228 11.6 2,775 242 58 13–14 189 10.0 2,375 205 49 14–15 200 12.5 3,000 233 56 14–15 173 10.2 2,450 197 47 15–16 200 13.3 3,175 224 53 15–16 173 10.4 2,500 188 45 16–17 186 13.9 3,325 216 52 16–17 167 10.5 2,500 184 44 17–18 186 14.3 3,400 210 50 17–18 167 10.5 2,500 184 44

Energy Requirements of Infants, Children and Adolescents 33 600 140

500 120

100 400

80 300 1985 FAO/WHO/UNU Energy requirements, kJ/kg per day requirements, Energy

2004 FAO/WHO/UNU 60 kcal/kg per day requirements, Energy 0 0 0 2 4 6 8 10 12 Fig. 1. Energy requirements for boys Age, months at 0–12 months of age.

600 140

500 120

100 400

80 300 1985 FAO/WHO/UNU

Energy requirements, kJ/kg per day requirements, Energy 2004 FAO/WHO/UNU 60 kcal/kg per day requirements, Energy 0 0 024681012 Fig. 2. Energy requirements for girls Age, months at 0–12 months of age.

Energy Requirements of Children and For boys: TEE (MJ/day) = 1.298 + 0.265 weight (kg) – Adolescents 2 2 0.0011 weight (kg ) SEE = 0.518 (eq. 2) TEE (kcal/day) = 310.2 + 63.3 weight (kg) – In the 2004 FAO/WHO/UNU report [1] , 0.263 weight2 (kg2 ) SEE = 124 DLW and heart rate monitoring were used to F o r g i r l s : predict the TEE of children and adolescents. TEE (MJ/day) = 1.102 + 0.273 weight (kg) – 2 2 TEE data of 801 boys and 808 girls aged 1–18 0.0019 weight (kg ) SEE = 0.650 (eq. 3) years were compiled from Canada, Denmark, TEE (kcal/day) = 263.4 + 65.3 weight (kg) – 0.454 weight2 (kg2 ) SEE = 155 Italy, Sweden, the Netherlands, Brazil, Chile, Columbia, Guatemala, and Mexico, from which During adolescence, gender diff erences in prediction equations for TEE were developed body size and composition are attenuated [12]. for boys and girls [10] . Th e energy cost of growth was based on mean rates of weight gain calculated from the WHO

34 Pediatric Nutrition in Practice 150 600

500

100 400

300

200 50 Light 100 Moderate Heavy Energy requirements, kJ/kg per day requirements, Energy Fig. 3. 2004 FAO/WHO/UNU energy kcal/kg per day requirements, Energy 1 0 0 requirements for boys at 1–18 years 024681012141618 of age at three levels of habitual Age, years physical activity.

150 600

500

100 400

300

200 50 Light 100 Moderate

Energy requirements, kJ/kg per day requirements, Energy Heavy Fig. 4. 2004 FAO/WHO/UNU energy kcal/kg per day requirements, Energy requirements for girls at 1–18 years 0 0 0 2 4 6 8 1012141618 of age at three levels of habitual Age, years physical activity.

weight-for-age standards [11] . The composition 23.6 kJ/g (5.65 kcal/g), or equivalent to 8.6 kJ/g of weight gained was assumed to be 10% fat with (2.1 kcal/g). energy content of 38.7 kJ/g (9.25 kcal/g), 20% The energy requirements of boys and girls protein with an energy content of 23.6 kJ/g (5.65 aged 0–18 years are summarized in tables 4, 5 kcal/g), or equivalent to 8.6 kJ/g (2.1 kcal/g). and figures 3, 4. During adolescence, gender differences in body size and composition are accentuated [12] . The energy cost of growth was based on Recommendations for Physical Activity mean rates of weight gain calculated from the WHO weight-for-age standards [11] . The com- A minimum of 60 min/day of moderate-intensity position of weight gained was assumed to be physical activity is recommended for children 10% fat with energy content of 38.7 kJ/g (9.25 and adolescents [1] , although there is no direct kcal/g), 20% protein with an energy content of experimental or epidemiological evidence on the

Energy Requirements of Infants, Children and Adolescents 35 minimal or optimal frequency, duration or inten- a moderate level of activity. To estimate the en- sity of exercise that promotes the health and well- ergy requirements of children with different lev- being of children and adolescents [13] . Regular els of habitual physical activity, a 15% allowance physical activity is often associated with de- was subtracted or added to the average PAL to creased body fat in both genders and, sometimes, estimate light (PAL = 1.5) and vigorous (PAL = increased fat-free mass at least in males. Physical 2.0) levels of activity in the 2004 FAO/WHO/ activity is associated with greater skeletal miner- UNU report. alization, bone density, and bone mass. Energy requirements must be adjusted in accordance with habitual physical activity. Torun C o n c l u s i o n s [14] compiled 42 studies on the activity patterns of 6,400 children living in urban, rural, industri- The energy requirements of infants, children and alized and developing settings from around the adolescents are defined as the amount of energy world. The TEE of rural boys and girls was 10, 15 needed to balance TEE at a desirable level of and 25% higher at 5–9, 10–14 and 15–19 years of physical activity, and to support optimal growth age, respectively, than their urban counterparts. and development consistent with long-term As part of the compilation of TEE values de- health [1]. Even though energy requirements also scribed above, physical activity level (PAL) values are presented for varying levels of physical activ- were estimated by using measured or predicted ity, moderately active lifestyles are strongly en- BMR [10] . The Schofield equations for BMR [3] couraged for children and adolescents to main- were used to predict PAL for children and adoles- tain fitness and health and to reduce the risk of cents, if not provided in the original publication. overnutrition. The average PAL (1.7) from these studies reflects

References

1 FAO/WHO/UNU Expert Consultation: 6 WHO Working Group on Infant Growth: 11 WHO: Measuring Change in Nutrition- Human Energy Requirements. Rome, An Evaluation of Infant Growth. al Status. Geneva, World Health Orga- World Health Organization, 2004. Geneva, Nutrition Unit, World Health nization, 1983. 2 Butte NF: Energy requirements of Organization, 1994, vol 94, pp 1–83. 12 Forbes GB: Human Body Composition.

infants. Public Health Nutr 2005; 8: 7 Butte NF, Wong WW, Hopkinson JM, et Growth, Aging, Nutrition, and Activity. 953–967. al Energy requirements derived from New York, Springer, 1987. 3 Schofield WN, Schofield C, James WPT: total energy expenditure and energy 13 Boreham C, Riddoch C: The physical Basal metabolic rate – review and pre- deposition during the first 2 years of activity, fitness and health of children.

diction, together with an annotated life. Am J Clin Nutr 2000; 72: 1558– J Sports Sci 2001; 19: 915–929. bibliography of source material. Hum 1569. 14 Torun B: Energy Cost of Various Physi-

Nutr Clin Nutr 1985; 39C:1–96. 8 Butte NF, Hopkinson JM, Wong WW, et cal Activities in Healthy Children. Ac- 4 Schoeller DA, Van Santen E: Measure- al: Body composition during the first tivity, Energy Expenditure and Energy ment of energy expenditure in humans two years of life: an updated reference. Requirements of Infants and Children.

by doubly labeled water method. J Appl Pediatr Res 2000; 47: 578–585. Lausanne, International Dietary En-

Physiol 1982; 53: 955–959. 9 de Bruin NC, Degenhart HJ, Gàl S, et al: ergy Consultancy Group, 1990, pp 139– 5 Berggren G, Christensen EH: Heart rate Energy utilization and growth in 183. and body temperature as indices of breast-fed and formula-fed infants 15 Energy and protein requirements. metabolic rate during work. Arbeits- measured prospectively during the first Report of a joint FAO/WHO/UNU Ex-

physiologie 1950; 14: 255–260. year of life. Am J Clin Nutr 1998; 67: pert Consultation. World Health Organ

885–596. Tech Rep Ser 1985; 724: 1–206. 10 Torun B: Energy requirements of children and adolescents. Public Health

Nutr 2005; 8: 968–993.

36 Pediatric Nutrition in Practice Koletzko B. (ed): Pediatric Nutrition in Practice. Basel, Karger, 2008, pp 37–41

1 General Aspects of Childhood Nutrition

1.3 Nutritional Needs

1.3.3 Protein

Paul Pencharz ؒ Rajavel Elango 1

Key Words Protein in the body is in a dynamic state re- -Protein ؒ Amino acids ؒ Requirement ؒ Infants ؒ ferred to as protein turnover, which involves con Children tinuous degradation to free amino acids, and re- synthesis of new proteins. The free amino acids are also constantly degraded and oxidized to car- Key Messages bon dioxide and nitrogenous end products, prin- R Diet must contain a balanced mixture of all amino cipally urea and ammonia. acids Dietary protein is necessary to replenish these R This can most easily be achieved by daily ingestion losses of amino acids to maintain protein homeo- of animal protein: an alternative is a complemen- stasis. Furthermore, in children, there is an in- tary mixture of plant proteins Copyright © 2008 S. Karger AG, Basel creased need for dietary protein to allow new tissue growth. The requirement of dietary protein is therefore composed of two components: maintenance Introduction and growth. The requirement of protein in children and Protein, derived from the Greek word proteos adults was analyzed in detail earlier [1, 2], and which means ‘primary’ or ‘taking first place’, is recently by the Institute of Medicine, Food and the major structural component of all cells in the Nutrition Board, US National Academy of Sci- body. ence in the Dietary Reference Intakes [3] . Proteins also function as enzymes, transport carriers, and as hormones; and their component amino acids are required for the synthesis of nu- Protein Requirement cleic acids, hormones, vitamins and other important molecules. Protein requirement is defined as the minimum The nutritional importance of proteins is due intake of high quality dietary protein (see Protein to their constituent amino acids. The 20 ␣ -amino Quality, below) that will provide the needs for acids which are part of proteins are classified maintenance at an appropriate body composi- based on their nutritional importance into indis- tion, and will permit growth at the normal rate pensable (essential) amino acids, conditionally for age, assuming energy balance and normal indispensable (essential) amino acids and dis- physical activity. pensable (nonessential) amino acids ( table 1 ). Expression of Requirement Table 1. Indispensable, conditionally indispensable and dispensable amino acids for humans

Protein requirement is expressed as the estimat- Indispensable Conditionally Dispensable ed average requirement (EAR), or the average re- indispensable quirement of the population. Due to the lack of conclusive data from em- Histidine Arginine Alanine pirical studies, the EAR is calculated by a facto- Isoleucine Cysteine Aspartic acid Leucine Glutamine Asparagine rial method which includes (1) requirement for Lysine Glycine Glutamic acid maintenance, estimated from Nitrogen Balance Methionine Proline Serine studies in children, and (2) requirement for Phenylalanine Tyrosine growth, estimated from rates of protein deposi- Threonine Tryptophan tion which are derived from body composition Valine analysis [4, 5], and the efficiency of protein utilization for each age group. The recommended dietary allowance (RDA) is the safe level of intake which will satisfy the protein needs of nearly all individuals (97.5%) in feeding of human milk for infants between 9 and the population. The RDA for protein is the EAR 12 months of age with appropriate introduction + two times the standard deviation of the EAR of of solid foods. The EAR and RDA are 1.0 and 1.2 each age group. g protein/kg body weight per day, respectively ( table 2 ).

Protein Requirements for Infants and Children: 1–18 Years Children Protein requirements for older children are calculated and recommended based on life stage Infants: 0–6 Months groups representing different velocities of growth Human milk is the optimal source of nutrients and endocrine status: toddlers (1–3 years), early for normal, full-term infants throughout the first childhood (4–8 years), puberty (9–13 years), and year of life and is recommended as the sole nutri- adolescence (14–18 years; table 2 ). During these tional source for infants during the first 4–6 stages, there is a continuing but slow decline in months of life. The recommended intakes of pro- protein needs relative to weight. The EAR deter- tein are based on an adequate intake (AI) that re- mined by the factorial method is set at the aver- flects the mean protein intake of infants fed hu- age for boys and girls in each age group except man milk. For infants at 0–6 months of age the adolescence (table 2 ). average milk intake is 0.78 liters/day and the average protein content of human milk is 11.7 g/l. Therefore, the AI for protein in infants at 0–6 Amino Acid Requirement for Infants and months is 9.1 g/day or 1.52 g/kg per day. Children

Infants: 7–12 Months The 9 indispensable amino acids (IAA; table 1 ) During the second 6 months of life, solid foods need to be obtained from the diet and, therefore, become a more important part of the diet of in- requirements have been defined for them. The fants and add a significant amount of protein to amino acid requirements (AI) for young infants the diet. The recommendation is for continued (0–6 months) are based on average human milk

38 Pediatric Nutrition in Practice Table 2. Protein requirement for infants, children and Table 3. Indispensable amino acid requirements for adolescents young infants at 0–6 months of age

Age Average requi- Safe level of Intake Adequate Intake rement (EAR) intake (RDA) per day intake per day g protein/kg g protein/kg g/day mg/kg per day mg/day body weight body weight per day per day Histidine 36 214 Isoleucine 88 529 7–12 months 1.0 1.2 11 Leucine 156 938 1–3 years 0.87 1.05 13 Lysine 107 640 4–8 years 0.76 0.95 19 Methionine + cysteine 59 353 9–13 years 0.76 0.95 34 Phenylalanine + tyrosine 135 807 14–18 years, boys 0.73 0.85 52 Threonine 73 436 1 14–18 years, girls 0.71 0.85 46 Tryptophan 28 167 Valine 87 519 Data from Dietary Reference Intakes 2002/2005 [3]. EAR = Estimated average requirement, calculated from Data from Dietary Reference Intakes 2002/2005 [3]. maintenance + growth (rate of protein deposition ! ef- Adequate intake calculated from the average volume ficiency of protein utilization); RDA = recommended di- of human milk intake and the mean indispensable etary allowance, calculated from EAR + 2 ! SD of EAR. amino acid content of human milk.

intake of 0.78 liters/day and the mean content of Protein Quality each indispensable amino acid in human milk (table 3). The requirement of protein is affected by not The EAR for IAA in older infants (7–12 only the quantity but also by the quality of the months) and children (1–18 years) are calculated protein source. Different sources of protein vary using the factorial method ( table 4 ). The method widely in their chemical composition and nutri- assumes that the maintenance requirement for tional value. The protein quality is determined each IAA is similar to adults and the require- principally by digestibility and the amino acid ments differ in children only by the growth needs. composition of the protein. The most important The requirement for growth is estimated from factor of the two is the relative content and met- the rate of protein deposition, amino acid com- abolic availability of the individual IAA. position of whole body protein and the efficiency If the content of a single IAA in the diet is less of protein utilization. than the individual’s requirements, then it will Recently we provided evidence that the main- limit the utilization of other amino acids and tenance requirements for adults and children are thus prevent normal rates of protein synthesis similar [6–8] . For a detailed review on the meth- even when the total nitrogen intake is adequate. ods to determine amino acid requirements refer Thus, the ‘limiting amino acid’ will determine to Pencharz and Ball [9] . the nutritional value of the total nitrogen or pro- The conditionally indispensable amino acids tein in the diet. ( table 1 ) are those that the infant or child is unable to produce in sufficient amounts and hence all or part of the daily needs for those amino acids must be provided by the diet.

Protein 39 Table 4. Indispensable amino acid requirement for older infants, children and adolescents

Age Average Safe level Age Average Safe level requirement of intake requirement of intake (EAR) (RDA) (EAR) (RDA) mg/kg mg/kg mg/kg mg/kg per day per day per day per day

7–12 months 9–13 years, girls Histidine 22 32 Histidine 12 15 Isoleucine 30 43 Isoleucine 17 21 Leucine 65 93 Leucine 38 47 Lysine 62 89 Lysine 35 43 Methionine + cysteine 30 43 Methionine + cysteine 17 21 Phenylalanine + tyrosine 58 84 Phenylalanine + tyrosine 31 38 Threonine 34 49 Threonine 18 22 Tryptophan 9 13 Tryptophan 5 6 Valine 39 58 Valine 22 27 1–3 years 14–18 years, boys Histidine 16 21 Histidine 12 15 Isoleucine 22 28 Isoleucine 17 21 Leucine 48 63 Leucine 38 47 Lysine 45 58 Lysine 35 43 Methionine + cysteine 22 28 Methionine + cysteine 17 21 Phenylalanine + tyrosine 41 54 Phenylalanine + tyrosine 31 38 Threonine 24 32 Threonine 18 22 Tryptophan 6 8 Tryptophan 5 6 Valine 28 37 Valine 22 27 4–8 years 14–18 years, girls Histidine 13 16 Histidine 12 14 Isoleucine 18 22 Isoleucine 16 19 Leucine 40 49 Leucine 35 44 Lysine 37 46 Lysine 32 40 Methionine + cysteine 18 22 Methionine + cysteine 16 19 Phenylalanine + tyrosine 33 41 Phenylalanine + tyrosine 28 35 Threonine 19 24 Threonine 17 21 Tryptophan 5 6 Tryptophan 4 5 Valine 23 28 Valine 20 24

9–13 years, boys Data from Dietary Reference Intakes 2002/2005 [3]. Histidine 13 17 EAR = Estimated average requirement, calculated from Isoleucine 18 22 maintenance + growth (rate of protein deposition ! Leucine 40 49 efficiency of protein utilization); RDA = recommended Lysine 37 46 dietary allowance, calculated from EAR + 2 ! SD of Methionine + cysteine 18 22 EAR. Phenylalanine + tyrosine 33 41 Threonine 19 24 Tryptophan 5 6 Valine 23 28

40 Pediatric Nutrition in Practice P r o t e i n S o u r c e s Conclusions

Protein from animal sources such as meat, poul- • For infants 0–6 months human milk is con- try, fish, eggs, milk, cheese, and yogurt provide sidered the ideal food and the protein intake all 9 IAA, and are called ‘high quality’ or ‘com- must be sufficient to maintain growth and plete proteins’. Protein from plants, legumes, meet other needs grains, nuts, seeds, and vegetables tend to be de- • The protein requirement for children is affect- ficient in one or more of the IAA and are called ed by both the quantity and quality of the pro- ‘incomplete proteins’. Specifically, cereal grains tein source are deficient in lysine and legumes are deficient • All indispensable amino acid requirements in methionine. Thus, for children who are active- must be met by the diet to ensure normal rates 1 ly growing, it is recommended to ensure suffi- of protein synthesis in healthy children cient intake of ‘high quality’ protein. Children • Therefore, consumption of ‘high quality’ pro- who restrict their diet to plant proteins should teins rich in the 9 indispensable amino acids, consume a varied diet containing complementa- principally animal sources such as meat, poul- ry mixtures of protein (e.g. rice with beans) to try, eggs, milk products and complementary ensure adequate protein intake. mixtures of plant protein, is recommended

References

1 Energy and protein requirements: 4 Butte NF, Hopkinson JM, Wong WW, et 7 Turner JM, Humayun MA, Elango R, et Report of a joint FAO/WHO/UNU Ex- al: Body composition during the first 2 al: Total sulfur amino acid requirement pert Consultation. World Health Organ years of life: an updated reference. of healthy school-aged children as

Tech Rep Ser 1985; 724: 1–206. Pediatr Res 2000; 47: 578–585. determined by indicator amino acid 2 Dewey KG, Beaton G, Fjeld C, et al: 5 Ellis KJ, Shypailo RJ, Abrams SA, Wong oxidation technique. Am J Clin Nutr

Protein requirements of infants and WW: The reference child and adoles- 2006; 83: 619–623.

children. Eur J Clin Nutr 1996; 50(suppl cent models of body composition. A 8 Humayun MA, Turner JM, Elango R, et 1):S119–S147. contemporary comparison. Ann NY al: Minimum methionine requirement

3 Institute of Medicine, Food and Nutri- Acad Sci 2000; 904: 374–382. and cysteine sparing of methionine in tion Board: Dietary Reference Intakes: 6 Mager DR, Wykes LJ, Ball RO, Pencharz healthy school-age children. Am J Clin

Energy, Carbohydrate, Fiber, Fat, Fatty PB: Branched-chain amino acid Nutr 2006; 84: 1080–1085. Acids, Cholesterol, Protein and Amino requirements in school-aged children 9 Pencharz PB, Ball RO: Different ap- Acids. Washington, National Acad- determined by indicator amino acid proaches to define individual amino

emies Press, 2002/2005. oxidation (IAAO). J Nutr 2003; 133: acid requirements. Annu Rev Nutr 3540–3545. 2003;23:101–116.

Protein 41 Koletzko B. (ed): Pediatric Nutrition in Practice. Basel, Karger, 2008, pp 42–46

1 General Aspects of Childhood Nutrition

1.3 Nutritional Needs

1.3.4 Digestible and Indigestible Carbohydrates C. Lawrence Kien

Key Words digestion), and indigestible. Examples of the for- -Carbohydrates ؒ Digestion ؒ Fermentation ؒ mer are lactose, sucrose, human milk oligosac Lactose ؒ Sucrose ؒ Oligosaccharides charides, and vegetable starch. Dietary fibers found in cereals, vegetables, and fruit and fructooligosaccharides such as inulin, present in cer- Key Messages tain vegetables and processed foods (e.g. pastry), R Dietary carbohydrate provides glucose, which al- are indigestible. Lactose may be only partially di- lows normal metabolism in the fed state, including gestible in preterm and, to some extent, in term insulin secretion, which inhibits body protein deg- infants and older children and adults who are not radation, thus maintaining normal amino acid bal- of northern European descent. Human milk oli- ance R Dietary carbohydrates are assimilated both by di- gosaccharides undergo little digestion and only gestion and bacterial fermentation, with absorp- about 10% of vegetable starch is not digested. tion of short-chain fatty acids and other bacterial Carbohydrates which are not digested and reach degradation products in the colon which have bio- the colon undergo bacterial fermentation to par- logical effects tially absorbed gases such as hydrogen and meth- R Certain indigestible carbohydrates may cause changes in the composition of the bacterial flora, a ane and to short-chain fatty acids (SCFA) such as so-called ‘prebiotic effect’ butyrate, which are efficiently absorbed in the R Some dietary carbohydrates may also be consid- colon. Butyrate has been reported to have many ered functional foods or ‘dysfunctional foods’ be- effects on mammalian cell gene transcription, cause their ingestion may alter bowel habits and protein synthesis, and both cellular proliferation the risk of disease processes such as type-2 diabe- and apoptosis. Besides being a source of substrate tes, obesity, colon cancer, and enteric infection Copyright © 2008 S. Karger AG, Basel for the production of compounds like butyrate, fermentable carbohydrates may also alter the composition of the colonic microflora (prebiotic effects), which can alter the risk of disease as well Introduction as having many potential effects on mammalian cell function via the largely unstudied properties Dietary carbohydrates may be categorized as po- of bacterial proteins. Certain carbohydrates, such tentially digestible by enzymes present in the sa- as dietary fiber, human milk oligosaccharides, liva, stomach, or intestine (or absorbable without and inulin, have effects on mammalian functions Dietary Carbohydrates

Small Intestine

Fructose Lactose Sucrose and Glucose Glucose, Galactose Starches Glucooligosaccharides Absorption Absorption Fructooligosaccharides Fiber

Colon Bacteria 1 Acetate, Propionate, Butyrate, Lactate (D, L), H , CH , etc. Absorption 2 4

Fig. 1. Overview of carbohydrate assimilation by the small intestine and Flatus colon.

independent of their nutrient value; these func- Digestible and Absorbable Carbohydrates tional (and ‘dysfunctional’) foods may alter the Monosaccharides (such as glucose and fructose), risk of type-2 diabetes, colon cancer, constipa- disaccharides (lactose, sucrose, maltose), and tion, inflammatory bowel disease, and enteric in- plant starch are digestible and/or absorbable. fection. However, lactose digestion diminishes progressively in older children, especially those who are not of northern European descent [2] . Mobile an- Carbohydrate Assimilation by the Small imals store most of their energy as fat because Intestine and Colon glycogen is hydrated and very heavy per unit kilocalorie. Plants store energy as starch, a mix- Overview ture of amylose (a polymer of maltose) and amy- Dietary carbohydrate is assimilated via intestinal lopectin, which has a structure similar to glyco- digestion and absorption, and via bacterial fer- gen. Plant starch exists in the form of small gran- mentation in the colon [1] . Fermentation may ules which generally escape milling; the crystalline have both beneficial and adverse effects on the structure of these granules determines their rela- infant [1] . SCFA produced via bacterial fermenta- tive susceptibility to digestion by mammalian tion are almost entirely absorbed in the colon and enzymes [3] . then partially (e.g. acetic acid) or more complete- Absorption of galactose and glucose per se ly (e.g. butyric acid) metabolized by the colonic increases the circulating concentration of glu- mucosa. SCFA then enter the liver where further cose with its attendant metabolic effects (via metabolism occurs. There is controversy over insulin secretion) [1] . Lactose digestion facili- whether lactose fermentation in the preterm tates calcium absorption [4] . Glucose is an im- newborn enhances the risk of necrotizing entero- portant source of energy for brain and other tis- colitis [1] . sues [1] .

Digestible and Indigestible Carbohydrates 43 Table 1. Carbohydrates as functional foods

Carbohydrate Putative functional effect Comment

Fiber/low glycemic Improved glucose tolerance/insulin Mechanism unknown index foods secretion Fructose ? Increased obesity/insulin resistance Low intakes from fruit not harmful; more human studies needed Fiber (bran) Decreased risk of colon cancer Fermentation may increase colon cell proliferation and increase risk Fiber, lactulose Decreased constipation Diarrhea with excessive intake Prebiotics Decreased inflammatory disease and Effects on cell proliferation appear variable enteric infection of the bowel; ? Effects of bacterial proteins on obesity Human milk Reduced intestinal bacterial adhesion Are there other oligosaccharides in food with oligosaccharides similar effects?

Indigestible Carbohydrates: Fiber, flora (such as ‘beneficial’ increases in bifidobac- Oligosaccharides and Prebiotics teria) [6] . Inulin also might alter colonic cell proliferation and modify the diarrhea caused by ‘Dietary Fiber’ lactulose [7] . In their cell walls, plants contain constituents not digestible by mammalian enzymes; these are collectively known as dietary fiber (cellulose, hemi- Functional and ‘Dysfunctional’ Carbohydrate cellulose, lignin, pectin, and gums) [3] . Foods: Foods May Have Functions Independent of Their Nutrient Content Oligosaccharides and Prebiotics (table 1) Besides lactose, human milk contains a complex mixture of oligosaccharides, which are almost Carbohydrates and the Risk of Diabetes [ 8 , 9 ] entirely fermented in the colon ( fig. 1 ) [4] . Fiber Type-2 diabetes develops, usually in insulin-re- and oligosaccharides have been added to both sistant people, when pancreatic ␤-cell function is formulas and infant foods [5] . Beyond infancy, insufficient to maintain euglycemia. The glyce- humans consume both glucooligosaccharides, mic response to various carbohydrate-contain- and fructooligosaccharides (FOS) such as inulin. ing foods has been characterized as the glycemic FOS are consumed mainly in pastry, confection- index [3, 8] . Low glycemic index foods, such as ery, and dairy products and also are found natu- breakfast cereal, whole wheat bread, pasta, bar- rally in such foods as onion [6] . The term ‘prebi- ley, parboiled rice, and legumes, tend to lessen otic’ has been applied to indigestible carbohy- the risk of type-2 diabetes [8] . Initial research drates, especially FOS such as inulin, which are emphasized the potential metabolic effects of almost quantitatively fermented in the colon and certain SCFA (e.g. propionate) and the effects of which tend to be selectively fermented by certain physical properties of fiber on slowing gastric bacteria, thus leading to changes in the colonic emptying and delaying or moderating glycemic

44 Pediatric Nutrition in Practice responses [3] . More recently it has been shown flammatory bowel disease [12] . Finally, there is that low glycemic index foods improve insulin emerging evidence that different bacterial spe- secretion by an unknown mechanism [8] . Inde- cies or strains may, via their protein products, af- pendent of the caloric content per se, a high fruc- fect mammalian gene expression and thus the tose intake, derived from the combined ingestion risk of health disorders such as obesity [7, 13] . of sucrose and high-fructose corn syrup (sweetened beverages and foods), may increase the risk Human Milk Oligosaccharides of obesity and insulin resistance because of the Human milk oligosaccharides may prevent bac- metabolic effects of fructose [9] . terial adhesion by interfering with the docking of bacteria on the intestinal cell surface and with Fiber and Colon Cancer the expression of certain enzymes in the intestine 1 For over 30 years, there has been controversy over required for bacterial adhesion [14] . whether higher intakes of fiber lower or increase the risk of colonic neoplasms [3, 10]. One hypoth- esized mechanism for a benefit of fiber relates to Conclusions the dilution effect of water adsorbed to non-fermentable fibers, which would dilute or ‘flush out’ • Supplementation of infant formula or infant carcinogens [3] . Another theoretical mechanism solid foods with fiber or inulin (prebiotics) for reduced colon cancer development is the in- may be warranted in some patients, but the hibition of cell proliferation by butyrate [1, 7] . In overall benefits to health are not clear cultured neoplastic cells of colonic origin, butyr- • High intakes of foods and beverages contain- ate generally causes a suppression of the cell cy- ing fructose or high-fructose corn syrup may cle, but in vivo, butyrate may have the opposite increase the risk of obesity, insulin resistance, effect [7] . Thus, highly fermentable fibers could and ultimately type-2 diabetes actually be detrimental [1, 3] . • Despite the controversy over the specific health benefits of fiber, a generous intake of Indigestible Carbohydrates Including Fiber and whole grains, fruits, and vegetables is recom- Constipation mended because of their nutrient content and Dietary fiber reduces constipation [11] . Inulin because such foods replace saturated, trans- also might increase the frequency of loose stools and polyunsaturated fat, and contain other [7] . Interestingly, preterm infants, who may have compounds with potentially advantageous ef- lactase deficiency at birth, thrive and seldom fects on health (e.g. tomato and lycopene) manifest diarrhea in response to human milk or formulas containing lactose as the sole carbohydrate [1] .

Prebiotics FOS may alter the bacterial colonization of the colon in favor of less clostridia, but the results of studies in humans are inconsistent [3, 5, 6] . Simi- larly, inulin has been shown to have both stimu- latory and inhibitory effects on colonic cell proliferation [7] . Both prebiotics and probiotics seem to have potential value in the treatment of in-

Digestible and Indigestible Carbohydrates 45 References

1 Kien CL: Digestion, absorption, and 7 Kien CL, Schmitz-Brown M, Solley T, et 11 Baker SS, Liptak GS, Colletti RB, et al: fermentation of carbohydrates in the al: Increased colonic luminal synthesis Constipation in infants and children:

newborn. Clin Perinatol 1996; 23: 211– of butyric acid is associated with low- evaluation and treatment. A medical 228. ered colonic cell proliferation in pig- position statement of the North Ameri-

2 Kien CL, Heitlinger LA, Li BU, Murray lets. J Nutr 2006; 136: 64–69. can Society for Pediatric Gastroenterol- RD: Digestion, absorption, and fermen- 8 Wolever TM, Mehling C: High-carbo- ogy and Nutrition. J Pediatr Gastroen-

tation of carbohydrates. Semin Perinat hydrate-low-glycaemic index dietary terol Nutr 1999; 29: 612–626.

1989; 13: 78–87. advice improves glucose disposition 12 Ewaschuk JB, Dieleman LA: Probiotics 3 Englyst KN, Englyst HN: Carbohydrate index in subjects with impaired glucose and prebiotics in chronic inflammatory

bioavailability. Br J Nutr 2005; 94: 1–11. tolerance. Br J Nutr 2002; 87: 477–487. bowel diseases. World J Gastroenterol

4 Klein CJ: Nutrient requirements for 9 Elliott SS, Keim NL, Stern JS, et al: 2006; 12: 5941–5950.

preterm infant formulas. J Nutr 2002; Fructose, weight gain, and the insulin 13 Backhed F, Ding H, Wang T, et al: The 132:S1395–S1577. resistance syndrome. Am J Clin Nutr gut microbiota as an environmental

5 Roy CC, Kien CL, Bouthillier L, Levy E: 2002; 76: 911–922. factor that regulates fat storage. Proc

Short-chain fatty acids: ready for prime 10 Fuchs CS, Giovannucci EL, Colditz GA, Natl Acad Sci USA 2004; 101: 15718–

time? Nutr Clin Pract 2006; 21: 351–366. et al: Dietary fiber and the risk of 15723. 6 Gibson GR, Roberfroid MB: Dietary colorectal cancer and adenoma in 14 Bode L: Recent advances on structure,

modulation of the human colonic mi- women. N Engl J Med 1999; 340: 169– metabolism, and function of human

crobiota: Introducing the concept of 176. milk oligosaccharides. J Nutr 2006; 136:

prebiotics. J Nutr 1995; 125: 1401–1412. 2127–2130.

46 Pediatric Nutrition in Practice Koletzko B. (ed): Pediatric Nutrition in Practice. Basel, Karger, 2008, pp 47–51

1 General Aspects of Childhood Nutrition

1.3 Nutritional Needs

1.3.5 Fats

Patricia Mena ؒ Ricardo Uauy 1

Key Words ment. Fat-soluble vitamins (A, D, E, K) require Lipids ؒ Essential fatty acids ؒ Linoleic acid ؒ dietary lipids for absorption. Fats provide flavor -Linolenic acid ؒ Long-chain polyunsaturated and texture to foods and thus affect taste and ac-␣ fatty acids ؒ Arachidonic acid ؒ Docosahexaenoic ceptability of diets. Membrane lipid composition -acid ؒ Saturated fatty acid ؒ Trans fatty acid defines in part the functional properties of mem branes (fluidity, transport properties, receptor activity, uptake and release of substances, signal Key Messages transduction and conduction and ion flows). FAs R Optimal lipid nutrition begins in fetal life with ad- can also have a direct effect on gene expression or equate n-3 to n-6 fatty acids and preformed long- by regulating transcription factors that affect the chain polyunsaturated fatty acid (LCPUFA) supply through the maternal diet expression of multiple other genes (i.e. peroxi- R Breast milk from mothers consuming a balanced some proliferator-activated receptors). Dietary diet provides the best source of bioavailable lipids lipids provide structural components for brain for term neonates and retinal structure, cell membranes, transport ␣ R Linoleic and -linolenic acids are essential fatty ac- of lipid components in plasma and form the only ids, in addition LCPUFAs are important for lifelong health true body energy store (adipose tissue). Fats and R LCPUFAs in the diet during the first months of life oils are key dietary factors affecting cardiovascu- are important for visual and congnitive develop- lar risk, obesity and diabetes. Linoleic acid (LA, ␣ ment, after that they contribute to lifelong health C18: 2n-6) and -linolenic acid (LNA, C18: 3n-3) R Trans fatty acids interfere with LCPUFA metabo- are essential, they serve as precursors for the lism, affect lipoprotein cholesterol regulation and long-chain polyunsaturated FAs (LCPUFAs), promote cardiovascular disease R The balance between dietary n-3 and n-6 is impor- such as arachidonic acid (AA, C20: 4n-6) and

tant to promote lifelong health, reducing disease docosahexaenoic acid (DHA, C22: 6n-3). Neural risk linked to allergic and inflammatory responses cell phospholipids in the retina and brain cortex Copyright © 2008 S. Karger AG, Basel are rich in DHA while vascular endothelia are rich in AA. LCPUFAs are precursors for eicosanoids (C20) and docosanoids (C22), which act Introduction as local and systemic mediators for clotting, immune, allergic and inflammatory responses; they Fats are the main source of energy for infants and also affect blood pressure, vessel and bronchial young children, and n-6 and n-3 fatty acids (FAs) relaxation and constriction. The dietary balance are essential for normal growth and develop- of n-6 and n-3 FAs can have profound influences in these responses, modulating the onset and se- coconut oil demonstrated typical skin lesions verity of multiple disease conditions (allergy, ath- and failed to gain weight compared to those given erosclerosis, hypertension and diabetes) [1, 5]. small amounts of energy from corn oil (2–4% to- Lipids were long considered as part of the ex- tal energy). This provided a strong base to main- changeable energy supply for infants and young tain that infant diets had sufficient LA, the n-6 children, thus the primary concern was the de- essential FA. A few decades later, in the late 1960s, gree of absorption of dietary fat as an important the advent of total parenteral nutrition providing contributor to the energy supply during early life protein and glucose as sole sources of nutrition [1, 8]. presented an opportunity to confirm that human infants require n-6 FAs for adequate growth. It was not until the 1980s that there was proof that Fats in the First Year of Life n-3 FAs are essential for humans, considering the altered visual function of a child receiving high High fat diets (40–60% energy) characteristic of n-6 parenteral lipids, which was reversed by pro- infant feeding contribute to the energy density of vision of LNA, the n-3 precursor found in soy oil. the diet required to support rapid weight gain, This was followed by information from nonhu- and especially to the fat accumulation observed man primates fed diets high in LA and extremely over the first year of life. This has been tradition- low in LNA before and after birth, which revealed ally considered a desirable trait considering the altered retinal function and visual maturational increased risk of infection and potential dietary delays in early life in animals given the low LNA inadequacy after 6 months of life. However, the diets. Studies in preterm infants postnatally fed need for this fat gain in terms of survival may corn oil (high in LA, low in LNA), soy oil (bal- need to be reexamined as we presently face an anced LA and LNA), soy + marine oil (providing environment that promotes energy excess and preformed DHA) or human milk (providing ad- thus increases the risk of obesity and chronic dis- equate LA, LNA and also preformed DHA) re- eases later in life. The recent 2006 WHO growth vealed that those receiving no DHA had altered standards based on predominant breastfeeding electrical responses to light and significant delays for the first 6 months of life suggest a leaner mod- in visual acuity maturation, which were only par- el of growth for the second semester of life (see tially improved by LNA. These studies served to Chapter 4.1). In addition, the recent FAO/WHO establish the need for LNA and suggested that at 2004 energy recommendations based on actual least for preterm infants DHA was also needed. energy expenditure from doubly labeled water Further studies over the past decade have estab- studies are substantially lower than the history lished a need for n-3 FAs in term infants, with based on reported intakes, suggesting that the some but not all studies demonstrating a benefit energy requirement and possibly the fat content of receiving preformed DHA. Several stable iso- after 6 months of life may need to be reexamined tope studies using labeled LA and LNA have (see Chapter 1.3.2) [7, 8, 10, 12]. demonstrated a limited and highly variable capacity to convert these precursors into the corre- sponding LCPUFAs, AA and DHA, supporting Essentiality of PUFAs and LCPUFAs the view that the latter may be considered conditionally essential during early life [1, 2, 9, 13]. The essentiality of fats for human nutrition was Artificial infant formulas based on mixes of identified only about 50 years ago when young vegetable oils (coconut, palm, corn, soy, sunflow- children given skimmed milk and hydrogenated er, safflower) provide LA- or oleic acid-rich for-

48 Pediatric Nutrition in Practice Table 1. Composition of commonly used vegetable oils

Source of oil Fat Saturates Mono- Poly- (n-6) (n-3) Choles- g unsaturates unsaturates PUFA PUFA terol, mg

Canola 100.0 7 59 30 20 9.3 0 Corn 100.0 13 24 59 58 0 0 Sunflower 100.0 10 19 66 66 0 0 Rapeseed 100.0 7 56 33 22 11.1 0 Soya 100.0 15 43 38 35 2.6 0 Olive 100.0 14 74 8 8 0.6 0 Vegetable solid fat 100.0 25 45 26 3 1.6 0 Animal fat lard 100.0 39 45 11 10 1 95 1 Milk fat 81 50 23 3 21 1.2 219

mulations and some LNA from soy oil attempting Table 2. Recommended fish as a source of EPA and to mimic human milk composition (table 1). Co- DHA [4, 14] conut oil fractions rich in medium-chain triglyc- Higher levels of EPA and DHA Herring erides are used in an effort to promote absorption, (>1,000 mg/100 g fish) Mackerel especially in the feeding of preterm infants and Salmon those with fat malabsorption syndromes since Tuna, bluefin C8–10 FAs are absorbed directly from the intesti- Greenland halibut nal mucosa passing to the portal vein and are not Medium level Flounder dependent on bile acid micelle formation for di- (500–1,000 mg/100 g fish) Halibut gestion, absorption and uptake as chylomicrons Tuna, canned white into the lymphatic ducts. Over recent years DHA Low level Tuna, skipjack or DHA+AA have been added to artificial formu- (<300 mg/100 g fish) Tuna, canned light Cod las. However, it is nearly impossible to fully repli- Catfish cate the unique fat composition and structure of Haddock human milk lipids. Human milk lipase activity further contributes to the improved fat digestibility of human milk. After 6 months, with the in- Table 3. Contribution of various food to trans fats con- troduction of solid complementary foods, egg sumed (percent of total) [14] yolk, liver and fish can provide preformed DHA and AA ( table 2 ) [3, 6, 14]. Food group % Total Cakes, cookies, crackers, pies, bread, doughnuts, fried fast chicken, etc. 40 Lipids in Human Milk Animal products 21 Stick margarine 17 Fried potatoes 8 Breast milk provides a ready source of both precur- Potato chips, corn chips, popcorn 5 sors and long-chain n-6 and n-3 derivatives, and is Household shortening 4 considered sufficient in these nutrients provided Breakfast cereals, candy 5 the mothers consume a nonrestrictive diet. The ac- Soy oil 2 tual amount of essential FAs and LCPUFAs present USDA analysis reported 0 g trans fats in salad dressing. in human milk varies depending on the maternal

Fats 49 Table 4. Fat supply for children older than 2 years for the prevention of nutrition-related chronic diseases (based on last seven references)

Dietary component Amount

Total dietary fat intake 30–40% of energy depending on activity Saturated fatty acids <10% of energy (mainly C12, C14, C16) Polyunsaturated fatty acids (PUFAs) 5–15% of energy n-6 PUFAs 4–13% of energy n-3 PUFAs 1–2% of energy n-6:n-3 ratio 5:1 to 10:1 Monounsaturated fatty acids No restriction within limits of total fat Cholesterol <300 mg/d Antioxidant vitamins Generous intake desirable Potentially toxic factors1 Trans fatty acids <2% of total energy Erucic acid <1% of total fat Lauric and myristic acids <10% of total fat Cyclopropenoids Traces Hydroperoxides Traces

1 Limit processed foods and hard fats and hard margarine as a practical way to reduce the intake of saturated and trans fatty acids.

diet. Human milk provides close to 50% of the en- atherogenic lipoprotein, but also lower high-den- ergy as lipids. Oleic acid is the predominant FA, sity lipoprotein (HDL) cholesterol, the protective while palmitic acid is provided in the sn-2 position lipoprotein responsible for reverse cholesterol of triglyceride, enhancing its absorption. Pre- transport. The net effect is that these fats contrib- formed cholesterol in breast milk (100–150 mg/dl) ute substantially in raising the risk of cardiovas- provides most of what is needed for tissue synthe- cular disease (table 3 ) [11, 12, 15]. sis, thus downregulating endogenous cholesterol synthesis in the initial months of life [7, 8]. Fats in the 2nd Year of Life and Beyond

Trans Fatty Acids After 2 years of life, the recommendations for fat need to consider the level of habitual physical ac- Trans FAs are the product of hydrogenation of tivity since the need for energy-dense food sources vegetable oils (soy) with the object of making such as fat should be adjusted to the energy re- these less susceptible to peroxidation (rancidity), quired to promote healthy weight and active liv- thus the processed foods prepared with trans FAs ing; the energy needs for growth after 2 years rep- have a longer shelf life, which is in the interest of resent 2–3% of the daily needs. Sedentary children producers and retailers. However, the effect of will meet their energy needs easily with fat energy these fats on lipoprotein metabolism is indeed of around 30% of the total, while active children more harmful than that of saturated fats (C14, may benefit from higher fat energy. Table 4 gives C16), since they not only increase low-density li- full details. Fat reduction has been advocated by poprotein (LDL) cholesterol, the cholesterol-rich some as a way to prevent diet-related chronic dis-

50 Pediatric Nutrition in Practice ease. There is clearly a need to promote energy bal- Conclusions ance and avoid energy excess that leads to unhealthy weight. This can be achieved by lowering • According to the breast milk model, the in- fat or sugar in the diet; in terms of weight control take of lipids for the first 6 months of life there may be some benefit from reducing sugar should provide 40–60% of total energy, an ! rather than fat with regard to insulin responses n-6:n-3 ratio of 5–10: 1, 1% industrially pro- and appetite control. In terms of cardiovascular duced trans FAs, and be free from erucic acid disease prevention, the key aspect is the quality of • After age 2 years, dietary fat should provide the fat: decreasing saturated fat (especially C14 30–35% energy: in the form of n-6 PUFAs 4– myristic and C16 palmitic acids) is crucial, in fact 10% energy, n-3 1–2% energy, saturated fat C18 stearic acid is neutral in terms of cholesterol, ! 10% energy, trans fats !2% energy 1 since most of it is converted to oleic acid by the • n-6 FAs should be limited to ! 10%, and total liver. Thus, a mild elevation in LDL cholesterol is PUFAs !15% of total energy, n-9 oleic acid can offset by a rise in HDL. The key issue in the pre- bridge the difference vention of obesity is keeping energy intake and ex- • The quality of the fat, more than the quantity, penditure in balance at a healthy weight. Reducing is important for lifelong health fat intake is one way of achieving this, but it may not be the most sustainable way [10, 12, 15].

References

1 Akabas SR, Deckelbaum SJ: Summary 7 Jensen CL: Effects of n-3 fatty acids 12 Working Group of the Canadian Pedi- of a workshop on n-3 fatty acids: cur- during pregnancy and lactation. Am J atric Society and Health Canada Nutri- rent status of recommendations and Clin Nutr 2006;83(6 suppl):1452S– tion Recommendations Update: Di-

future directions. Am J Clin Nutr 2006; 1457S. etary Fat and Children. Ottawa, Health

83(suppl): S1536–S1538. 8 Uauy R, Castillo C: Lipid requirements Canada, 1993. 2 Arterburn LM, Bailey Hall E, Oken H: in infants: Implications for nutritional 13 Koletzko B, Lien E, Agostoni C, Böhles Distribution, interconversion and dose composition of fortified complemen- H, Campoy C, Cetin I, Decsi T, Duden-

response of n-3 fatty acids in humans. tary foods. J Nutr 2003; 133:2962S– hausen JW, Dupont C, Forsyth S, Hoesli

Am J Clin Nutr 2006; 83(suppl): S1467– 2972S. I, Holzgreve W, Lapillone A, Putet G, S1476. 9 Lewin GA, Schachter HM, Yuen D, et Secher NJ, Symonds M, Szajewska H, 3 Straarup EM, Lauritzen L, Faerk J, et al: Effects of Omega-3 Fatty Acids on Willatts P, Uauy R: The roles of long- al: The stereospecific triacylglycerol Child and Maternal Health. Evidence chain polyunsaturated fatty acids in structures and fatty acids profiles of Report/Technology Assessment No. 118 pregnancy, lactation and infancy: re- human milk and infant formulas. (Prepared by the University of Ottawa view of current knowledge and consen-

J Pediatr Gastroenterol Nutr. 2006; 42: Evidence-Based Practice Center, under sus recommendations. J Perinat Med 293–299. Contract No. 290-02-0021). AHRQ 2008;36:5–14. 4 FDA and EPA Announce the Revised Publication No. 05-E025-2. Rockville, 14 Aggett PJ, Haschke F, Heine W, et al: Consumer Advisory on Methylmercury Agency for Healthcare Research and Comment on the content and composi- in Fish. March 04.http://www.fda.gov/ Quality, 2005. tion of lipids in infant formulas. bbs/topics/news/2004/ NEW01038.html. 10 Gidding SS, Dennison BA, Birch LL, et ESPGAN Committee on Nutrition. Acta

5 Oh R: Practical applications of fish al; American Heart Association: Paediatr Scand 1991; 80: 887–896. oil (omega-3 fatty acids) in primary Dietary recommendations for children 15 Department of Health and Human Ser-

care. J Am Board Fam Pract 2005; 18: and adolescents: a guide for practitio- vices and Department of Agriculture.

28–36. ners. Pediatrics 2006; 117: 544–559. Dietary Guidelines for Americans 6 Rodriguez M, Funke S, Fink M, et al: 11 FAO/WHO Report of a Joint Expert 2005, chapter 6 fats. http://www.health. Plasma fatty acids and [13C]linoleic Consultation (1994): Fats and Oils in gov/dietaryguidelines/dga2005/. acid metabolism in preterm infants fed Human Nutrition. FAO Food and Nutri- a formula with medium-chain triglyc- tion Paper No. 57. Rome, Food and Agri-

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Fats 51 Koletzko B. (ed): Pediatric Nutrition in Practice. Basel, Karger, 2008, pp 52–56

1 General Aspects of Childhood Nutrition

1.3 Nutritional Needs

1.3.6 Fluid and Electrolytes George J. Fuchs

Key Words contraction, the most common cause worldwide being infectious diarrheal disease resulting in de- Fluids ؒ Electrolytes ؒ Rehydration hydration. Unlike sodium, whose distribution in the Key Messages body is uneven because of active transport of the R Maintenance of body water is principally governed ion, water movement is passively determined in by the kidney except in pathologic states such as re sponse to osmotic gradients. Body water, being diarrheal disease freely diffusible, is therefore in equilibrium in R Intestinal transportation of water and electrolytes relation to the distribution of its nondiffusable is a finely tuned phenomenon regulated by com- solutes. plex interaction between endocrine, paracrine, immune, and enteric nervous systems Maintenance of body water involves the con- R Cotransportation of Na+ with glucose, SGLT-1, is trol of both intake/absorption governed by the preserved in most diarrheal diseases and forms the gastrointestinal tract and excretion, but princi- basis for oral rehydration solution pally by excretion controlled by the kidney. Un- R Breastfed infants, including low birth weight in- der normal conditions, losses via the gastrointes- fants, in hot climates do not require supplemental tinal tract are small but can greatly increase in water R Oral rehydration solution should be used for re- pathologic states such as diarrheal disease. hydration and accomplished rapidly over 3–4 h Diarrheal illness accounts for approximately except in severe dehydration or intolerance of en- 2.5 million deaths per year, with most deaths oc- teral fluids Copyright © 2008 S. Karger AG, Basel curring in developing countries and many of these from dehydration [1] . The severity of dehydration is graded by clinical signs and symptoms that reflect fluid loss and that determine the treatment Introduction regimen to correspond to the degree of severity. Regardless of the etiology, more than 90% of dehy- Maintenance of body water and electrolytes is the dration can be safely and effectively managed with result of tightly regulated balances of intakes and oral rehydration therapy using a prescribed fluid outputs mediated by elaborate physiologic mech- and electrolyte oral rehydration solution (ORS). anisms. Sodium (Na +) retention causes volume Because malnutrition results in an increased fre- expansion and depletion causes volume contrac- quency, severity, and duration of diarrhea, fluid tion. A net negative sodium balance results in a and electrolyte replacement and nutritional ther- clinical state of extracellular fluid (ECF) volume apy are the critical elements for recovery [2] . Regulation of Sodium Balance Gastrointestinal Regulation of Fluids and Electrolytes Sodium absorption occurs in the gastrointestinal tract and excretion primarily by the kidney with In general, permeability of the tight junction be- small amounts excreted in sweat and feces. In tween epithelial cells decreases distally so that pathologic conditions, especially diarrheal dis- the jejunum is the most and the distal colon and ease, normal gastrointestinal mechanisms of ho- rectum the least permeable to the passive move- meostasis become disturbed and can result in ment of electrolytes and water [5] . Ions traverse large, sometimes life-threatening fluid and elec- the epithelium by passing through the transcel- trolyte losses. The systems regulating renal so- lular or paracellular routes throughout the length dium chloride (NaCl) and water excretion oper- of the bowel by passive or active transport mech- 1 ate by a negative feedback loop consisting of an anisms. Passive movement of fluids follows, with afferent (sensory) component, an efferent (mes- paracellular transport, the main mechanism of senger) component, and an effector organ [3] . flow in the small bowel, and transcellular flow The renal response is aimed at reconstituting predominating where the epithelia are tightly ECF volume by decreasing the glomerular filtra- aligned and less permeable as in the distal colon. tion rate and thus the filtered load of Na + and, Cotransportation of Na + with certain nutrients even more critically, by promoting tubular reab- including glucose and amino acids at the apical sorption of Na+ utilizing the various mechanisms surface of the upper villus in the small intestine of Na + transport including exchangers, channels, is responsible for most Na+ and water absorption and cotransporters. Receptors located in the re- following a meal or ingestion of oral rehydration nal juxtaglomerular apparatus detect reduced solution (fig. 1). The carrier specific for Na-glu- ECF volume and Na + concentration, and stimu- cose cotransportion, SGLT-1, is preserved in most late renal Na+ retention via the renin-angiotensin diarrheal diseases and thereby forms the basis for cascade. oral rehydration therapy [6] . In the fasted state or between meals, most NaCl is transported from + – – – the lumen via exchange (Na /H and Cl /HCO 3). Regulation of Body Water While sodium transport drives fluid absorption, Cl– excretion is the driving force for fluid Plasma osmolality is the primary driver for thirst secretion. Cl is taken up along the basolateral and, therefore, water intake, although under con- membrane of the epithelial cell by the electroneu- ditions of reduced ECF volume, such as severe de- tral Na+ /K +/2Cl – cotransporter and accumulates hydration, low blood volume assumes a greater within the cell above its electrochemical equilib- role and will override tonicity [4] . Arginine vaso- rium (fig. 2). Once within the cell, Cl exits into pressin secreted from pituitary neuronal cells in the intestinal lumen via Cl channels that open in response to signals from osmoreceptors binds to response to regulatory agonists that invoke sec- epithelial cell basolateral receptors of the other- ond messenger systems. wise water-impermeable nephron collecting tu- bule, stimulating insertion of water channels (aquapores) into the apical cell surface and re- Intracellular Regulators of Ion Flux sults in extraordinary movement of water from lumen to cell interior. A variety of hormones, neurotransmitters, and secretagogues bind to receptors along the epithelial cell membrane to initiate the intracellular

Fluid and Electrolytes 53 Na+ – Glucose 2Cl GLUT-2 + NKCC1 SGLT-1 CFTR K Glucose 2Na+ 2K+ Cl– Na+ 3Na+ 2K+ 3Na+ Na+, K+- Na+, K+- ATPase ATPase

Cl– K+

Fig. 1. Cotransportation of sodium and glucose. Fig. 2. Chloride excretion and fluid secretion.

Intercellular Regulators of Ion Flux 3.0

2.5 Under normal conditions, intestinal transport of 2.0 water and electrolytes is a finely tuned transcel- Hot and humid 1.5 lular and paracellular phenomenon regulated by the complex interaction between the endocrine, 1.0 paracrine, immune, and enteric nervous systems. Sweat rate, liters/h rate, Sweat 0.5 Cool and dry In reality, these systems do not function as iso-

0 lated units and their borders are indistinct and overlap [4] . Examples include serotonin and va- 160 200 240 280 320 Running speed, m/min soactive intestinal peptide that function as either hormones or neurotransmitters or both depend- 109 8 7 6 5 ing on the precise physiologic situation. Certain Running speed, min/mile bacterial enterotoxins such as cholera and cyto- toxins simultaneously stimulate paracrine, neu- Fig. 3. The effect of ambient temperature, humidity, and exertion (running speed) on approximate rate of sweat- ral, and immune responses, all of which may alter ing in adults. From Sawka and Montan [8] . ion and water flux [7] . cascade involving the second messenger mole- Other Regulatory Factors cules of cyclic nucleotides (including cyclic adenosine monophosphate and cyclic guanosine Other factors influence fluid and electrolyte monophosphate) and ionized cytosolic calcium transport indirectly and include acid-base ho- (Ca2+ ). These in turn activate protein kinases that meostasis, gut motility, luminal flow rates, intes- exert direct control of ion channels to increase ef- tinal permeability, blood oncotic pressure and flux of Cl through Cl channels down their elec- plasma volume, venous and arterial pressure, and trochemical gradients and inhibition of electro- physical and psychological stress. neutral NaCl-coupled influx.

54 Pediatric Nutrition in Practice Table 1. Treatment of acute watery diarrhea, modified from King et al. [10]

Degree of Signs Rehydration therapy Replacement Nutrition dehydration (within 4 h) of losses

Minimal Well, alert Not applicable For each diarrheal Continue (<3%) stool or vomiting breastfeeding episode give: or resume 60–120 ml ORS age-appropriate if <10 kg b.w., diet after initial 120–240 ml ORS rehydration if >10 kg b.w. Mild to Sunken eyes, sunken fontanelle, ORS 50–100 ml/kg Same as above Same as above 1 Moderate loss of skin turgor, dry buccal over 3–4 h (3–9%) mucous membranes Severe Signs of moderate dehydration Intravenous fluids Same as above (≥10%) with one of the following: 30 ml/h until pulse, If unable to drink, rapid thready pulse, cyanosis, perfusion, and mental give by nasogastric cold extremities, deep breathing, status improve; then tube lethargy, unconscious ORS 100 ml/kg over 4 h

Effects of Environment and Physical Activity etiology. Except for severe dehydration or if the child is not able to tolerate enteral fluids, oral Heat stress and physical activity may cause both ORS (Na+ ) should be used for rehydration and ac- fluid and electrolyte imbalances. In hot climates, complished rapidly over 3–4 h (table 1) [10] . a considerable volume of water may be lost WHO and UNICEF recommend a 245-mmol/l through perspiration for evaporative cooling and ORS of NaCl 2.6 g (75 mmol/l), glucose 13.5 g (75 is further increased with increased humidity and mmol/l), KCl 1.5 g (20 mmol/l), and citrate 2.9 g during periods of physical exertion ( fig. 3 ) [8] . (10 mmol/l). Breastfeeding should continue dur- Compared to adults, children have a greater suring and immediately following rehydration; in face area to body mass ratio but lower sweating non-breastfed infants, an unrestricted age-ap- capacity and that has more important implica- propriate diet should be provided immediately tions for heat tolerance than fluid and electrolyte following initial rehydration. If formula is being disturbances. Breastfed infants, including low used, it should not be diluted and does not need birth weight infants, in hot climates can be ade- to be a specialized formula since lactose-contain- quately maintained on breast milk exclusively ing formulas are usually well tolerated. Ongoing and do not require supplemental water [9] . stool losses should be replaced with ORS. Severely dehydrated children usually require initial rehydration with intravenous fluids, after Principles of Rehydration and Fluid which hydration can usually be maintained oral- Maintenance ly with ORS (table 1). Ringer’s lactate (Na + 130 mmol/l, K+ 4 mmol/l, Cl– 109 mmol/l and lactate The degree of dehydration as graded by clinical 28 mmol/l) with or without 5% dextrose is the characteristics determines the fluid and electro- preferred intravenous solution while normal sa- lyte regimen to be used, regardless of the specific line (0.9% NaCl; Na + 154 mmol/l) is an acceptable

Fluid and Electrolytes 55 Table 2. Guidelines for intravenous fluids for severe dehydration Age First give Then give 30 ml/kg overa 70 ml/kg overb

Infants (<12 months) 1 h 5 h Older children and adults 30 min 2.5 h

Modified from WHO [2]. Preferably start intravenous Ringer’s lactate (with or without 5% dextrose; normal saline is acceptable) immediately; give an oral rehydration solution until the intravenous line is started if the child can drink. a Repeat once if radial pulse remains weak or not detectable. b If the child is able to drink and keep up with stool losses, introduce ORS as described in table 1.

alternative. In extreme situations or if the child is breastfeeding in breastfed infants and early unable to keep up with ongoing stool losses, in- refeeding during a diarrheal disease episode. travenous fluids are needed beyond the initial re- Zinc supplementation promotes recovery from hydration period (table 2 ) [2] . acute and persistent diarrhea; as well as decreas- In developing countries where diarrheal dis- ing post-diarrheal disease morbidity, it is now ease is most prevalent and associated with the universally recommended as adjunctive treat- greatest mortality and morbidity, many affected ment of children with diarrhea older than 6 children have concomitant malnutrition. Malnu- months of age. Severely malnourished children trition results in an increased incidence, severity, with diarrhea have unique, stereotypical clinical and duration of diarrhea and is an underlying abnormalities and require a specific, protocolized cause of much of the diarrheal disease-related regimen to ensure safe, efficacious fluid and elec- mortality. Optimal prevention and management trolyte reconstitution. A potential role for zinc in of diarrheal disease, therefore, requires atten- the treatment of acute diarrhea in developed tion to nutritional therapy including continued countries has not been defined.

References

1 Kosek M, Bern C, Guerrant RL: The lytes. Philadelphia, Saunders, 1996, Gastrointestinal Tract. New York, Ra- global burden of diarrhoeal disease as pp 63–109 . ven Press, 1995 . estimated from studies published be- 5 Sellin JH: Intestinal electrolyte absorp- 8 Sawka MN, Montan S: Fluid and elec- tween 1992 and 2000. Bull World tion and secretion; in Feldman M, trolyte supplementation for exercise

Health Organ 2003; 81: 197–204. Scharschmidt BF, Sleisenger MH (eds): heat stress. Am J Clin Nutr 2000; 2 WHO: The Treatment of Diarrhoea: A Sleisenger and Fordtran’s Gastrointes- 72(suppl):564S–572S. Manual for Physicians and Other Se- tinal and Liver Disease: Pathophysiol- 9 Cohen RJ, Brown KH, Rivera LL, Dew- nior Health Workers. Geneva, WHO, ogy, Diagnosis, Management. Philadel- ey KG: Exclusively breastfed, low birth- 2005. www.who.int/child-adolescent- phia, Saunders, 1998 . weight term infants do not need sup-

health/New_Publications/CHILD_ 6 Hirschhorn N, Greenough I: Progress plemental water. Acta Paediatr 2000;

HEALTH/ISBN_92_4_159318_0.pdf. in oral rehydration therapy. Sci Am 89: 550–552.

3 Trachtman H: Sodium and water ho- 1991; 264: 50–56. 10 King CK, Glass R, Breese JS, Duggan C: meostasis. Pediatr Clin North Am 7 Cho JH, Chang EB: Intracellular media- Managing acute gastroenteritis among

1995; 42: 1343–1363. tors and mechanisms of pathogen-in- children. MMWR 2003; 52: 1–16. www. 4 Sterns RH, Spital A, Clark EC: Disor- duced alterations in intestinal electro- cdc.gov/mmwr/preview/mmwrhtml/ ders of water balance; in Kokko JP, lyte transport; in Blaser MJ, Smith PD, rr5216a1.htm. Tannen RL (eds): Fluids and Electro- Ravdin JI, et al (eds): Infections of the

56 Pediatric Nutrition in Practice Koletzko B. (ed): Pediatric Nutrition in Practice. Basel, Karger, 2008, pp 57–61

1 General Aspects of Childhood Nutrition

1.3 Nutritional Needs

1.3.7 Vitamins and Trace Elements Noel Solomons 1

Key Words have been established. These apply exclusively to -Vitamins ؒ Minerals ؒ Fortification ؒ Supplements ؒ healthy infants, toddlers, children and adoles Toxicity cents. The net supply of nutrients available to a child, however, is determined by a series of factors described in table 1 . Key Messages R Micronutrients (vitamins and trace elements) are essential for growth and health Sources of Vitamins and Trace Elements R They are obtained naturally from foods as well as through fortification and enrichment and by con- The three principal sources of micronutrients for suming supplements R There are important nutrient–nutrient interactions a child are described in table 2 . All nutrients will among micronutrients be obtained from one or another of these for- R Excessive intake of certain vitamins and trace ele- mats. ments can have adverse effects on child health Copyright © 2008 S. Karger AG, Basel Vitamins and Trace Elements Intrinsic to Foods It takes a wide variety of different foods to obtain the entire range of necessary micronutrients in Introduction adequate amounts [1] . Micronutrients tend to be less varied and less dense in edible plants than in The same set of organic compounds and inorgan- animals [2] . In addition, cooking, processing and ic elements that are essential for adults are simi- storage destroy or elute nutrients before con- larly indispensable for children of all ages, from sumption. Moreover, it is important to under- premature infants to individuals in late adoles- stand the recent consensus that the vitamin A cence. These include a total of 13 vitamins, 4 of value of the provitamin A carotenes found in which are classified as fat-soluble and 9 of which green, orange and yellow fruits and vegetables is are classified as water-soluble. There are also only one half of what had traditionally been con- some 9 inorganic trace elements which are classi- sidered [3] . It would take twice as many servings fied as essential to human nutrition or beneficial of carrots or broccoli to provide a given contribu- to human health. Age- and gender-specific rec- tion to daily vitamin A needs than would have ommended dietary intakes of the micronutrients been estimated 8 years ago. Table 1. Factors conditioning the absorption and utiliza- The richest sources of certain nutrients may tion of dietary micronutrients be cellular animal tissue items, such as red meat, Antinutritional constituents liver and other visceral organ meats. These ani- Substances in the diet can reduce the absorption or uti- mal tissue sources, however, may be problematic lization of essential nutrients. For example, phytic acid in two ways: (1) these food items are generally blocks the absorption of iron and zinc. Lead contamina- among the least accessible and affordable in the tion interferes with the utilization of iron for red cell for- child populations at greatest risk of deficiency, mation and (2) excessive dependence on animal sources Gastrointestinal health for nutrition collides with guidelines to moderate The secretory and absorptive integrity of the alimentary tract can be compromised by frequent diarrhea, consumption of cholesterol, saturated fats and Helicobacter pylori, and parasitoses red meat in order to lower the risk of chronic non-communicable diseases [5] . Viscera may be Efficiency of metabolic retention Once absorbed, a series of adverse factors related to excessively rich in vitamin A. Moreover, some intestinal and renal function, the intactness of the in- marine fish may have heavy metal contaminants, tegumentary system and systemic immune responses, while herbicides and pesticides can contaminate among others, can lead to excess wastage of nutrients inland river and lake fish. On the other hand, other vitamins/micronutrients are found in the diet, namely in grains, fruits and vegetables. Biofortification is a new approach using con- Table 2. Sources of micronutrients for human consump- ventional and biotechnology-genetic techniques tion to increase the density of nutrients in plants [6] , including inducing the uptake of nutrients into Intrinsic micronutrients Nutrients contained within the tissue matrix and fluid grains and tubers that are not usually found in of edible items from the animal and plant kingdoms abundance, e.g. iron in rice, ␤ -carotene (provita- Extrinsic (added) micronutrients min A) in maize and cassava. Nutrients are added to foods as enrichment, in mass fortification by public health mandate, and/or with dis- Vitamins and Trace Elements Added to Foods cretionary fortification, as in commercial foods or with Extrinsic addition of micronutrients usually oc- nutrient mixes added to complementary foods in the curs in processing, or occasionally in the home home prior to consumption. There are three important Supplemental micronutrients domains for addition of vitamins and minerals to Nutrients taken in pharmaceutical preparations (chew- able candies, tablets, elixirs) in individual or combined foods: enrichment (adding back the levels of nu- formats trients lost in processing); public health-directed fortification (adding a nutrient to a widely consumed item, such as iodine to salt, vitamin A to oil or sugar, folic acid to flour to counter a dietary deficit), and market-driven fortification (adding To the extent that plants are rich sources of nutrients to commercial foods to enhance their vitamins E, C, K and folate, children should be market appeal) [7] . In the latter regard, certain encouraged to consume whole grains and green, breakfast cereals, when consumed with milk, yellow and orange vegetables to take advantage of provide the entire adult daily micronutrient re- these sources. Picky eaters are at a disadvantage quirement with a single serving. Such a serving in covering their required nutrient intakes from would exceed the requirements for most juve- the basic diet [4] . niles, except for adolescents.

58 Pediatric Nutrition in Practice Table 3. Selected nutrient–nutrient interactions of importance in pediatric nutrition

Vitamin–vitamin interactions Vitamin E–vitamin A There is a mutual antagonism between these two vitamins Vitamin A–vitamin D Excessive intake of preformed vitamin A can antagonize the action of vitamin D Folate–vitamin B12 Excess intake of folate masks the hematological manifestations of vitamin B12 deficiency Vitamin–Element interactions Vitamin D–calcium Work synergistically to assure the appropriate level of mineral accretion in bone Vitamin C–iron Enhances the absorption of iron from plant sources in the diet Vitamin E–selenium Work synergistically to cover antioxidant protection of membrane and cytosolic zones of cells Vitamin A–iodine Vitamin A deficiency concomitant with severe iodine deficiency increases the size of goiters, but prevents hypothyroidism 1 Vitamin A–iron Vitamin A adequacy is required for full hematopoietic efficiency of iron incorporation into red cells Riboflavin–iron Riboflavin adequacy is required for full hematopoietic efficiency of iron incorporation into red cells Element–Element Interactions Iron–zinc Iron and zinc exert a mutual competitive interaction for sites of intestinal absorption Calcium–iron Calcium interferes with the absorption of both inorganic and heme iron from the diet Calcium–phosphorus Both inadequate or excessive intake of phosphorus will disturb the homeostatic regulation of calcium in the circulation Iodine–selenium Selenium deficiency in combination with deficiency of iodine may be required for the hypothyroid (myxedematous) goiter phenotype

Processed complementary foods, for con- mat is self-prescribed multivitamin supplemen- sumption while an infant is in transition from ex- tation, in which families provide vitamins, trace clusive breastfeeding (or infant formula feeding) elements or both (usually both in a multivitamin- to full weaning, should be fortified with micro- mineral combination) to children. Pediatric vita- nutrients. Because of the much higher iron re- min-mineral supplements in attractive, candy- quirements from 6- to 12-month olds as com- like presentations provide the entire pediatric pared to the 2nd year of life, the recommendable recommended intakes and are commonly con- iron levels are quite distinct, whereas the micro- sumed and marketed throughout the world. If a nutrient density of the other micronutrients can child is healthy enough to absorb and retain the be relatively constant [8] . A recent innovation for nutrients, deficiency states would be prevented discretionary home fortification of complemen- by such practices. tary foods is the use of iron and multinutrient An important aspect for the pediatrician is ‘sprinkles’ to infant’s and toddler’s foods. supplementation for specific therapeutic or prophylactic aims in at-risk groups. Iron and calcium Vitamin and Trace Element Supplementation given to preterm infants is one example. In adoles- This has two formats. There is public health-di- cent practice where precocious pregnancy is a risk, rected supplementation, as for vitamin A in coun- attention to supplements of folic acid (to prevent tries with endemic hypovitaminosis, in which neural tube defects), iron (to build stores), and io- supplements (e.g. capsules) are distributed peri- dine (to prevent cretinism, if in a goiter zone) odically to vulnerable age groups. The other for- would be important preventive considerations.

Vitamins and Trace Elements 59 Public health-directed supplementation for Table 4. A listing of some pertinent paradoxical associa- children is a logistic challenge. Vitamin A cap- tions and precautions related to dietary exposure to micronutrients sule distribution has been the basis of child-survival programs in low-income societies. Daily The upper tolerable levels for zinc in toddlers and pre- iron-folic acid supplementation has been recom- school children may be too low, as they are lower than mended for 6- to 24-month-old children in areas the average amounts of zinc consumed by apparently of anemia endemicity [9] , but the presence of ma- healthy children in the United States laria may be a strong contraindication [10] . Zinc The traditional ideal is that all members of a family unit is the newest nutrient to be added to population- share the majority of meals as a family. However, the upper tolerable level of preformed vitamin A for chil- wide pediatric distribution in developing coun- dren under 6 years is lower than the recommended dai- tries with widespread stunting and child mortal- ly intake of total vitamin A for pregnant or lactating ity [11] . women in the same household Specific supplements with doses of vitamins The currently recommended intake levels for vitamin D, and minerals above the recommended daily al- especially for adolescents and for individuals from lowances, with the express purpose of improving darkly pigmented ethnic groups living in temperate lat- health or preventing diseases, have limited scien- itudes such as Europe, North America, and southern Australia, may not be sufficient to maintain protective tific basis. Self-prescribing of mega-dose regi- circulating levels of the vitamin. Pediatric dermatolo- mens to children should generally be discour- gists and nutritionists are in confrontation about sun aged, as this practice runs the risk of: (1) over- exposure. The dermatology community advocates loading the child with excessive amounts of the maximal sunscreen protection to avoid skin damage and malignancy risk, whereas maximizing vitamin D nutrient, and (2) relying on an inadequate and formation in skin at temperate latitudes requires relax- unproven intervention when evidence-based al- ation of total solar avoidance ternative treatment may be readily available. An upward spiral of market-driven fortification, with multiple manufacturers adding micronutrients to make their products more attractive and ‘nutritious’, runs the Additional Theoretical and Practical Caveats risk of providing children who consume these products and Precautions regarding Vitamin and Trace with several times the daily recommended amounts of some vitamins Element Nutrition Folic acid fortification is mandated in many countries for the prevention of neural tube defects in the preg- Certain ethnic, climatic, environmental or en- nancies of susceptible women. These higher folic acid demic disease conditions may modify the needs, intakes have additional benefits for adults for preven- generally in a manner to increase the amounts tion of stroke and vascular disease. However, for adults needed to obtain adequate nutrient concentra- with established dysplastic changes in the large bowel tions in body reserves or sites of their metabolic mucosa, higher folic acid exposure accelerates the progression to colorectal cancer. The implications of or structure roles. It should also be recognized these – beneficial and harmful – effects for a pediatric that the highest daily intake recommendations population are currently unknown for some micronutrients of any period during the Epidemiological evidence is accumulating that con- lifespan occur in the adolescent years. sumption of preformed vitamin A from animal sources The overall balance among micronutrients, and fortificants weakens bone mineralization. The ex- both in the diet and in the body, has implications tent and importance of such a process in childhood merits research attention because of a series of recognized nutrient–nutrient interactions between vitamins, between trace elements and across the classes [12] . Selected examples are illustrated in table 3 . Many of these

60 Pediatric Nutrition in Practice have important implications for the formulation Conclusions of diets and multinutrient formulations. Both the Food and Nutrition Board of the • Vitamin and trace elements get into the child United States and the European Food Safety Au- from natural foods and beverages, fortified thority of the European Union have established products and multimicronutrient supple- upper tolerable intake levels for certain micronu- ments; each of these sources can be applied to trients, whose intake beyond a certain daily correct dietary inadequacy amount could be unsafe for the consumer. The • The weaning period is a major challenge to interplay between essential risk of dietary defi- providing adequate trace elements to the in- ciency and interventions to enhance micronutri- fant and toddler ent status leads to a series of paradoxical situa- • In the community setting, gastrointestinal 1 tions and evokes the need for certain precautions. pathogens and antinutritional substances in A selection of these are outlined in table 4 . the diet can adversely affect micronutrient ad- Future research is likely to reveal enzyme equacy polymorphisms that commonly differentiate a • The convergences of sources from self-supple- greater or lesser susceptibility to defective utili- mentation and expanding market-driven food zation of dietary nutrients [13] , as has currently fortification pose a short-term risk for vita- been discovered with folic acid. min and trace element over nutrition for some segments of the pediatric population

References

1 Steyn NP, Nel JH, Nantel G, et al: Food 6 Sautter C, Poletti S, Zhang P, Gruissem 10 Sazawal S, Black RE, Ramsan M, et al: variety and dietary diversity scores in W: Biofortification of essential nutri- Effects of routine prophylactic supple- children: are they good indicators of tional compounds and trace elements mentation with iron and folic acid on dietary adequacy? Public Health Nutr in rice and cassava. Proc Nutr Soc admission to hospital and mortality in

2006; 9: 644–650. 2006; 65: 153–159. preschool children in a high malaria 2 Dwyer J: Convergence of plant-rich and 7 Allen LH, de Benoist B, Dary O, Hurrell transmission setting: community-

plant-only diets. Am J Clin Nutr 1999; R: Guidelines for Food Fortification. based, randomised, placebo-controlled

70:S620–S622. Geneva, World Health Organization, trial. Lancet 2006; 367: 133–143. 3 West CE, Eilander A, van Lieshout M: 2006. 11 Black RE: Zinc deficiency, infectious Consequences of revised estimates of 8 Dewey KG: Nutrient composition of disease and mortality in the developing

carotenoid bioefficacy for dietary con- fortified complementary foods: should world. J Nutr 2003; 133(suppl 1):S1485– trol of vitamin A deficiency in develop- age-specific micronutrient content and S1499.

ing countries. J Nutr 2002; 132(suppl): ration sizes be recommended? J Nutr 12 Kubena KS, McMurray DN: Nutrition

S2920–S2926. 2003; 133:S2950–S2952. and the immune system: a review of 4 Carruth BR, Skinner J, Houck K, et al: 9 Stoltzfus RJ, Dreyfuss ML: Guidelines nutrient-nutrient interactions. J Am

The phenomenon of ‘picky eater’: a be- for the Use of Iron Supplements to Pre- Diet Assoc 1996; 96: 1156–1164. havioral marker in eating patterns of vent and Treat Iron Deficiency Anemia. 13 Ames BN, Elson-Schwab I, Silver EA:

toddlers. J Am Coll Nutr 1998; 17: 180– Washington, ILSI Press, 1998. High-dose vitamin therapy stimulates 186. variant enzymes with decreased coen- 5 Solomons NW, Anderson AS: Raising zyme binding affinity (increased meat consumption in a contemporary K(m)): relevance to genetic disease and

world. Asia Pac J Clin Nutr 2004; 13: polymorphisms. Am J Clin Nutr 2002;

116–119. 75: 616–658.

Vitamins and Trace Elements 61 Koletzko B. (ed): Pediatric Nutrition in Practice. Basel, Karger, 2008, pp 62–66

1 General Aspects of Childhood Nutrition

1.4 Physical Activity: Impact on Child Health and Nutritional Needs Robert M. Malina

Key Words ical fitness. Settings and types of PA (sport, play, -Physical activity ؒ Physical fitness ؒ Energy education, work, ‘exercise’, etc.) are strongly in . [expenditure ؒ Movement fluenced by culture [1 PF is a state or a condition which permits the individual to carry out daily activities, including Key Messages PA, without undue fatigue and with sufficient re- R Regular physical activity (PA) is important for bio- serve to enjoy active leisure pursuits. PF includes logical growth and maturation and behavioral de- muscular strength and endurance, flexibility, car- velopment diovascular and motor components. Morphologi- R Children should participate in 60 min or more of dai- cal and metabolic indicators have been added to the ly, moderate-to-vigorous PA that is developmentally appropriate and enjoyable more traditional concept of PF. Components of PF R PA can be an important component in preventing are related to PA at generally moderate levels [1, 2]. unhealthy weight gain leading to obesity Low levels of PA and PF are independent risk R Proﬁ ciency in movement skills, PA and PF are redu- factors for chronic disease and premature mor- ced under conditions of persistent undernutrition tality among adults. Increased prevalence of obe- Copyright © 2008 S. Karger AG, Basel sity and risk factors and emergence of symptoms of metabolic and cardiovascular diseases during childhood and adolescence highlight the impor- Introduction tance of PA and PF in preventive contexts [3] . On the other hand, persistence of chronic undernu- The business of ‘growing up’ – physical growth, trition in many parts of the world compromises biological maturation and behavioral develop- the PA and PF of youth [1] . ment – is complex and places many demands upon children and adolescents. Physical activity (PA) and physical fitness (PF), among other fac- Measurement tors, are important in these processes. PA is a behavior involving movement of the Methods for estimating the habitual level of PA body through space. It is viewed most often in and energy expenditure (EE) are summarized in terms of energy expenditure and stresses and table 1 . None of the methods covers all aspects of strains associated with weight bearing and PA and EE; a combination of methods is needed ground reaction forces. PA has a performance to obtain a comprehensive estimate of the habit- component in specific movement skills and phys- ual level of PA and EE of an individual. Choice of Table 1. Commonly used methods for the assessment of pattern and/or level of PA and EE

Method Function Advantages Drawbacks Comment assessed

Questionnaire PA Simple, low cost; suitable Relies on memory; hard The shorter the recall period the higher for large-scale studies to quantify; low validity the validity Interview PA More valid than a Relies on memory Interviewer can corroborate information questionnaire Diary PA Short recall time Interactive Depends on child’s interpretation

Direct PA, (EE?) No need for recall; Expensive; depends on ‘Gold standard’ for specific behavioral observation context documented observer’s skill aspects of activity 1 Time-lapse video PA, (EE?) Objective, hard record Child is limited to Less expensive than direct observation or photography available predetermined area Movement PA, (EE?) Objective, little Do not detect specific counters interaction; low cost movements Accelerometry PA, EE(?) Same as counters, plus Does not detect specific Some validity vs. measurements of EE acceleration activities

HR monitoring EE Little interaction; HR affected not only by Needs individual ‘calibration’ vs. VO2 inexpensive metabolism

VO2 metabolic EE Measures metabolism Limited activities; need for Useful for ergometry and cart mouthpiece or facemask VO2–HR ‘calibration’

VO2 portable EE Measures metabolism Highly interactive; Limited pediatric use in prolonged equipment away from the laboratory expensive observations

VO2 canopy EE Measures metabolism RMR only Used in conjunction with HR monitoring Respiration EE Precise measurement Very limited quarters; Validating other tests; ideal for BMR chamber of EE expensive Doubly labeled EE Best measure of EE; Very high cost; requires ‘Gold standard’ for average EE, but not water not interactive at least 1 week for profile of EE

PA = Physical activity; EE = energy expenditure; HR = heart rate; RMR = resting metabolic rate; BMR = basal metabolic rate. A question mark denotes uncertain validity. Reproduced with permission from Malina et al. [1].

methods depends on the specific objectives of a parent during the second decade. Estimated EE study/survey, age of subjects, equipment and per- is, on average, greater in males than in females sonnel. Surveys of PA and PF in various countries and the difference between the sexes increases are summarized elsewhere [2] . with age. EE in PA is the most variable component of EE. The ratio of total EE (TEE) to resting EE (REE) provides an estimate of the contribu- Variation with Age and Sex tion of activity-related EE to TEE over 24 h. It is expressed as the physical activity level (PAL), Estimated 24-hour EE (kcal/kg) based on doubly which increases with age during childhood and labeled water declines with age, beginning in ear- adolescence in youth from industrialized coun- ly childhood (fig. 1). The decline is especially ap- tries, but more so in youth from rural areas and

Physical Activity: Impact on Child Health and Nutritional Needs 63 studies and PA contexts show a decline during 90 adolescence [1, 2] . The physical environment and a variety of biological, social and psychological

70 factors influence patterns and levels of PA. PA is a characteristic that is at best moderately

Boys stable across childhood into adolescence [5] . The 50 seeming instability reflects individual differenc- EE, kcal/(kg · 24 h) es, age variation and limitations of assessment Girls 30 methods. Activities of young children tend to be 135791113151719 largely non-organized, spontaneous, and com- Age, years prised of intermittent brief bouts, while those of older children and adolescents tend to be more organized, regular and prolonged. The PA needs Fig. 1. Estimated energy expenditure (EE) per kilogram body mass in healthy children and adolescents based on of children and adolescents vary with age doubly labeled water. Drawn after Torun et al. [4] . ( fig. 2 ).

Benefits of Physical Activity

100 Regular PA does not alter linear growth and bio- 90 logical maturation as ordinarily observed, but is 80 important in the regulation of body weight and 70 60 for the integrity of skeletal muscle and bone tis- 50 Childhood: Adolescence: sues [1] . Health benefits of PA in school-age youth

40 Activities largely Increased capacity are summarized in table 2 . 30 intermittent for continuous activities

Relative emphasis, % emphasis, Relative 20 10 0 How Much Activity? 2 4 6 8 10 12 14 16 18 Age, years The majority of intervention and experimental studies with school-age youth use programs of moderate-to-vigorous PA 30–45 min, 3–5 days/ Fig. 2. Schematic illustration of activities and activity needs with increasing age in childhood and adoles- week [3] . A greater amount of PA is probably cence. – – – = General physical activity, emphasis on mo- necessary to achieve beneficial effects of PA un- tor skills; –––– = prescriptive physical activity, emphasis der free living conditions in which activities are on health, fitness, behavioral outcomes. Modified from often intermittent and unsupervised. According- Malina [12] . ly, school-age youth need 60 min or more of moderate-to-vigorous PA on a daily basis [3] . Chil- dren ! 5 years probably need a similar amount of cities of developing countries [1, 4] . Active chil- daily PA, but the types and duration of specific dren have a PAL of about 1.7–2.0. activities are likely to vary. Nevertheless, activi- The level of PA, on average, changes little or ties for children and adolescents of all ages should increases slightly with age during childhood be developmentally appropriate and enjoyable and declines during adolescence. Though not all and should include variety.

64 Pediatric Nutrition in Practice Table 2. Summary of beneficial effects of regular physi- Energy Expenditure, Physical Activity and cal activity (PA) on indicators of health, fitness and be- Nutrition havior in school-age children and adolescents

1 Adiposity: Comparisons of fatness of active and less Energy and protein requirements to support nor- active youth are equivocal. Moderate-to-vigorous mal growth are highest in early infancy and sub- PA programs have a minimal influence on adiposity sequently decline. After about 2 years of age, only in normal weight youth, but such programs are as- a small percentage of energy and protein intake sociated with a reduction in adiposity in obese youth supports growth, i.e., increase in size; the major portion supports tissue maintenance or replace- 2 Lipids and lipoproteins: A variety of intervention studies indicates a weak beneficial effect of PA on ment. Energy required for PA is the most variable HDL-cholesterol and triglycerides, but no effect on component of overall EE [1] . 1 total cholesterol and LDL-cholesterol 3 Blood pressures: There is no clear association between PA and blood pressures in normotensive Undernutrition youth. Experimental PA programs which improve aerobic fitness have a beneficial effect on blood Chronic undernutrition during infancy and early pressures in hypertensive youth childhood results in compromised growth, de- 4 Metabolic syndrome: Few studies have evaluated layed development of proficiency in movement the impact of PA on metabolic syndrome in youth, but several features of the syndrome cluster with in- skills and reduced PA. School-age children of mar- dicators of physical activity and inactivity and car- ginal to poor nutritional status show decreased to- diorespiratory fitness. Elements of the syndrome, tal daily EE and PA. This is related in part to small- specifically reduced insulin and triglycerides, are as- er body size. Reduced PA may limit movement sociated with PA in obese youth skills in play and games, and in turn contribute to 5 Bone mineral content: A variety of studies consis- performance-fitness deficiencies [1]. Quasi-exper- tently shows beneficial effects of regular PA on bone imental observations suggest that mild-to-moder- mineral content and density in youth ately undernourished boys differ from nutrition- 6 Aerobic fitness: Aerobic fitness is higher in active ally normal boys in the capacity to increase EE in than less active youth. Programs of continuous vigorous aerobic PA are associated with a gain of about PA [6, 7]. They simply cannot keep up with better

ml/(kg ؒ min)) in maximal aerobic fitness nourished boys during sport activities. Intestinal 4–3) 10% 7 Muscular strength and endurance: Comparisons of parasite load associated with chronic undernutri- active and less active youth show equivocal results tion may influence PA and PF. Treatment of for muscular strength and endurance, but data for school-age undernourished children for hook- upper body measures suggest better performances worm, whipworm and roundworm is associated

in active youth. Experimental strength (resistance) with increasing spontaneous PA, improving car- training programs are associated with gains in strength and endurance diovascular fitness and improving growth and appetite [8, 9]. A related factor is illness; during peri- 8 Other benefits and risks: Other benefits associated with PA among youth include improved global self- ods of illness, children tend to be less active. concept and a reduction in anx iety and depression symptoms. Risk of injury is associated with PA, but the health, fitness and behavioral benefits outweigh Obesity the risks

Adapted from Strong et al. [3]. Energy costs of PA differ between the obese and non-obese. Absolute EE is greater in obese children and adolescents, but after adjusting for dif-

Physical Activity: Impact on Child Health and Nutritional Needs 65 ferences in body size or composition, EE is simi- Conclusions lar in the obese and non-obese [10] . Data based on questionnaires, heart rate or time and motion • Regular PA is important for biological growth analyses suggest that obese children and adoles- and maturation and behavioral development cents are less active than their lean peers [11] . The • Regular PA has significant health promotion PF of obese children and adolescents is compro- and disease prevention functions mised on tasks that require movement or projec- • Children should participate in 60 min or more tion of the body through space, e.g., runs and of daily, moderate-to-vigorous, developmen- jumps. Mechanically, excess fat represents an in- tally appropriate, enjoyable PA ert load (dead weight) which must be moved. • The amount of PA needed to prevent un- Obese youth are also characterized by reduced healthy weight gain is not known cardiovascular fitness. On the other hand, obese • Proficiency in movement skills, PA and PF are youth are absolutely stronger and more powerful reduced under conditions of persistent under- in tasks that do not require movement or projec- nutrition tion of the body [1] . • Chronically low levels of PA are often implicated in childhood obesity, but data for low levels of habitual EE/PA as a primary causative factor in obesity are relatively scant

References

1 Malina RM, Bouchard C, Bar-Or O: 6 Spurr GB, Reina JC: Undernutrition, 10 Bar-Or O, Foreyt J, Bouchard C, et al: Growth, Maturation, and Physical Ac- physical activity, and performance of Physical activity, genetic and nutrition- tivity, ed 2. Champaign, Human Kinet- children; in Blimkie CJR, Bar-Or O al considerations in childhood weight ics, 2004. (eds): New Horizons in Pediatric Exer- management. Med Sci Sports Exerc

2 Malina RM, Katzmarzyk PT: Physical cise Science. Champaign, Human Ki- 1998; 30: 2–10. activity and fitness in an international netics, 1995, pp 149–159. 11 Goran MI: Energy expenditure, body growth standard for preadolescent and 7 Spurr GB: Physical activity and energy composition, and disease risk in chil- adolescent children. Food Nutr Bull expenditure in undernutrition. Prog dren and adolescents. Proc Nutr Soc

2006; 27:S295–S313. Food Nutr Sci 1990; 14: 139–192. 1997; 56: 195–209. 3 Strong WB, Malina RM, Blimkie CJR, 8 Adams EL, Stephenson LS, Latham 12 Malina RM: Fitness and performance: et al: Evidence based physical activity MC, Kinoti SN: Physical activity and adult health and the culture of youth;

for school youth. J Pediatr 2005; 146: growth of Kenyan school children in Park RJ, Eckert HM (eds): New Pos- 732–737. with hookworm, Trichuris trichiura sibilities, New Paradigms? American 4 Torun B, Davies PSW, Livingstone and Ascaris lumbricoides infections Academy of Physical Education Papers, MBE, et al: Energy requirements and are improved after treatment with No. 24. Champaign, Human Kinetics,

dietary energy recommendations for albendazole. J Nutr 1994; 124: 1199– 1991, pp 30–38. children and adolescents 1 to 18 years 1206.

old. Eur J Clin Nutr 1996; 50:S37–S81. 9 Stephenson LS, Latham MC, Adams EJ, 5 Malina RM: Physical activity and fit- et al: Physical fitness, growth and ap- ness: pathways from childhood to petite of Kenyan school boys with

adulthood. Am J Hum Biol 2001; 13: hookworm, Trichuris trichiura and 162–172. Ascaris lumbricoides infections are improved four months after a single

dose of albendazole. J Nutr 1993; 123: 1036–1046.

66 Pediatric Nutrition in Practice Koletzko B. (ed): Pediatric Nutrition in Practice. Basel, Karger, 2008, pp 67–70

1 General Aspects of Childhood Nutrition

1.5 Early Nutrition and Long-Term Health Berthold Koletzko

1 Key Words Biological programming has been defined as: ‘either the induction, deletion, or impaired develop- ؒ Metabolic programming of long-term health -Developmental origins of adult health ؒ ment of a permanent somatic structure or the “set Breastfeeding and obesity ؒ Perinatal nutrition ؒ ting” of a physiological system by an early stimulus Disease risk prevention or insult operating at a “sensitive” period, resulting in long-term consequences for function’ [2] . While the term programming was introduced into the Key Messages scientific literature by Dörner [3] already in 1974, R Nutritional and metabolic factors during sensitive, the concept has received broad attention primar- limited periods of early human development have ily due to epidemiological studies published by a long-term programming effect on health, wellbeing and performance in later age, extending into Barker et al. [4] documenting inverse relation- adulthood and old age ships between bodyweight at birth and at age 1 R Evidence for early programming effects arises from year, respectively, and the risks of hypertension, in vitro experiments, animal models, retro- and diabetes and coronary heart disease ( fig. 1 ) in prospective epidemiological studies, and first con- adulthood. These observations raised the hypoth- trolled intervention trials esis that maternal and fetal malnutrition during R Obstetric and pediatric medicine are expected to achieve a much greater future role for prevention pregnancy induce both fetal growth restriction of long-term disease risks in the population and increased later disease risk, whereas recent R The important effects on health of early nutrition data suggest that accelerated weight gain after programming justify major investments into re- birth, which is associated with a low birthweight, search and improvement of practice might be a causal factor. The exploration of un- Copyright © 2008 S. Karger AG, Basel derlying mechanisms and the resulting effects of metabolic programming offers tremendous opportunities for early prevention of major health Introduction risks already during pregnancy and infancy, and they could provide both obstetric and pediatric Epidemiological studies, numerous animal mod- medicine with a markedly increased role in pro- els and clinical intervention trials provide ample moting long-term health of the population. evidence that nutritional and metabolic factors The concept of early metabolic programming during sensitive, limited periods of early human of long-term health is supported by physiological, development have a long-term programming ef- epidemiological and clinical research [1, 5–7]. fect on health, well-being and performance in lat- Experimental in vitro studies and in vivo animal er age, extending into adulthood and old age [1] . studies elucidate the primary molecular path- 2.5 2.5

p = 0.001 p < 0.001 2.0 2.0

1.5 1.5

1.0 1.0

0.5 0.5

0 0 <5.5 5.6–6.5 6.6–7.5 7.6–8.5 8.6–9.5 >9.5 <18 19–20 21–22 23–24 25–26 >27 Birthweight, lb Weight at 1 year, lb

Fig. 1. Retrospective epidemiological studies reported an inverse relationship between infant body weight at birth (in British pounds) and the adjusted risk of death from coronary heart disease from the age of 65 year onwards. Drawn from the data of Barker et al. [4]. ways by which altered maternal nutrition either fed and formula-fed infants, we assessed the po- during pregnancy or lactation results in offspring tential long-term impact of breastfeeding on later being at an increased risk of later disease. Spe- body weight in a large cross-sectional survey of cific mechanisms by which later disease is pro- more than 9,000 children participating in the grammed are defined, and the precise nutritional obligatory school health examination in Bavaria, conditions that contribute to these processes are Germany [8] . An assessment of early feeding, established. Evidence is accumulating that epi- diet, and lifestyle factors revealed a clearly higher genetic programming of the genome altered by prevalence of obesity in children who had never early nutritional interventions plays a major role. been breastfed (4.5%) than in breastfed children Also explored are critical windows during early (2.8%), with an inverse dose-response effect be- development when nutrition programs one or tween the duration of breastfeeding and the prev- more chronic degenerative diseases, such as obe- alence of later obesity. The protective effect of sity, cardiovascular disease, metabolic syndrome, breastfeeding was not attributable to differences diabetes, renal disease, allergy, autoimmune dis- in social class or lifestyle. After adjusting for po- ease, and cancer. It is important to elucidate tential confounding factors, breastfeeding re- whether these outcomes are genotype-depen- mained a significant protective factor against the dent, and to which extent they might be reversible development of obesity (OR 0.75, 95% CI 0.57– and could be overcome by later nutritional or 0.98) and overweight (OR 0.79, 95% CI 0.68–0.93), pharmacological interventions. with a dose-response relation between breast- As an important example of nutritional pro- feeding duration and later risk of overweight and gramming in humans, the relationship between obesity, respectively ( fig. 2 ). A protective effect of infant feeding and later obesity will be discussed breastfeeding was also found in a number of here. Since many studies reported somewhat dif- studies in other populations, whereas others ferent growth patterns of populations of breast- found no benefit. Systematic reviews and meta-

68 Pediatric Nutrition in Practice analyses of cohort, case-control or cross-section- 1.00 al studies concluded that breastfeeding provides a small but consistent protective effect [9–11] .

However, these conclusions are only based on ob- 0.75 servational data because healthy infants cannot be assigned to breastfeeding on a randomized basis, and hence residual confounding cannot be 0.50 excluded with certainty. The only published cluster randomized trial on breastfeeding promotion

Adjusted odds ratio found no effects on later obesity, but basically all 0.25 infants participating in this trial in Belarus had 1 been breastfed, and the intervention only influ- 0 enced the duration of breastfeeding. Thus, this <2 3–5 6–12 >12 study does not allow conclusions on the effects of Breastfeeding duration, months early breastfeeding versus formula feeding [12] . Various hypotheses have been raised on po- Fig. 2. The risk for overweight (white columns; BMI 1 90th tential causes for a protective effect of breastfeed- centile) and obesity (black columns; BMI 1 90th centile) at ing. The establishment of a biological plausibility school age, adjusted for relevant confounding factors, and the elucidation of mechanisms which medi- decreases with longer duration of breastfeeding in more than 9,000 German children. A small but consistent effect ate the protective effect of breastfeeding would of breastfeeding on later obesity was confirmed in many lend support to a causal effect of breastfeeding. other studies around the world. Drawn from the data of We proposed that the protective effect of breast- von Kries et al. [8] . feeding is at least in part due to lower growth rates in the first year, as compared to formula-fed infants, and is mediated by a lower protein con- childhood BMI, corrected for parental BMI [1] . tent of human milk relative to formula [1] . Thus, a high protein intake with infant formula Populations of breastfed infants show higher in excess of metabolic requirements might pre- weight and length gains during the first year of dispose to an increased obesity risk in later life, a life than formula-fed infants, whereas more rapid concept referred to as the ‘early protein hypoth- weight gain in infancy and the second year of life esis’. This question is being studied in a large ran- predisposes to childhood overweight and obesity domized clinical trial with allocation of healthy [13–16] . These growth differences of breast- and term infants to formulae with higher and lower formula-fed populations are most likely due to protein contents (the European Childhood Obe- differences in metabolizable substrate intakes. sity Project, www.metabolic-programming.org). Infants at the ages between 3 and 12 months have First results indicate that lowering of protein sup- a 10–18% higher energy intake per kilogram ply, reaching values which are close to intakes bodyweight if fed formula as compared to breast- provided by breast milk, normalizes growth up fed infants. The difference in protein intake per to the age of 2 years, compared with the growth kilogram bodyweight is even larger: it is 55–80% of breastfed populations. Further follow-up of higher in formula-fed than in breastfed infants the participating children should reveal whether [1] . In epidemiological studies, high protein in- this diet-induced normalization of early growth takes in early childhood, but not the intakes of patterns will exert long-term health effects. energy, fat or carbohydrate, were significantly re- This is but one example of the numerous op- lated to an early adiposity rebound and to a high portunities that should arise from a better under-

Early Nutrition and Long-Term Health 69 standing of early metabolic programming and its • Breastfeeding, compared to formula-feeding, underlying mechanisms. Further elucidation of is associated with a small but consistent risk the impact of early nutrition on long-term health reduction for overweight and obesity at later is expected to contribute greatly to providing im- ages, which is of considerable public health proved policies of nutrition both for women dur- relevance on a population basis ing pregnancy and lactation and their infants, • High weight gain in infancy and the second and to enhancing standards of practice. year of life predicts an increased risk of later overweight and obesity. Thus, it is prudent to avoid feeding practices that lead to excessive Conclusions weight gain in early life

• Optimal nutrition during pregnancy, lactation, and infancy is important not only for im- Acknowledgments mediate outcomes such as fetal and infant weight gain and body composition, but also This work has been supported in part by the Commission of the European Communities, within the 6th Frame- has long-term effects on child health, well- work Programme, contract no. 007036. This article does being and performance extending into adult- not necessarily reflect the views of the Commission and hood and old age in no way anticipates the future policy in this area.

References

1 Koletzko B, Dodds P, Akerblom H, Ash- 8 von Kries R, Koletzko B, Sauerwald T, from a large randomized trial. Am J

well M (eds): Perinatal Programming of von Mutius E, Barnert D, Grunert V, Clin Nutr 2007; 86: 1717–1721. Adult Health – EC Supported Research von Voss H: Breast feeding and obesity: 13 Kramer MS, Chalmers B, Hodnett ED,

Series. Berlin, Springer, 2005. cross sectional study. BMJ 1999; 319: Sevkovskaya Z, Dzikovich I, Shapiro S, 2 Lucas A: Programming by early nutri- 147–150. Collet JP, Vanilovich I, Mezen I, Ducru-

tion in man. Ciba Found Symp 1991; 9 Arenz S, Ruckerl R, Koletzko B, von et T, Shishko G, Zubovich V, Mknuik D,

156: 38–50. Kries R: Breast-feeding and childhood Gluchanina E, Dombrovskiy V, Ustino- 3 Dörner G: Perinatal hormone levels and obesity – a systematic review. Int J Obes vitch A, Kot T, Bogdanovich N,

brain development; in Stumpf WE, Relat Metab Disord 2004; 28: 1247–1256. Ovchinikova L, Helsing E; PROBIT Grant LD (eds): Anatomical Neuroen- 10 Ip S, Chung M, Raman G, Chew P, Ma- Study Group: Promotion of Breastfeed- docrinology. Basel, Karger, 1975, pp gula N, DeVine D, Trikalinos T, Lau J: ing Intervention Trial (PROBIT): a ran- 245–252. Breastfeeding and Maternal and Infant domized trial in the Republic of Bela-

4 Barker DJ, Hales CN, Fall CH, Osmond Health Outcomes in Developed Coun- rus. JAMA 2001; 285: 413–420. C, Phipps K, Clark PM: Type 2 (non- tries. Evidence Report/Technology 14 Toschke AM, Grote V, Koletzko B, von insulin-dependent) diabetes mellitus, Assessment, No. 153. Rockville, Agency Kries R: Identifying children at high risk hypertension and hyperlipidaemia for Healthcare Research and Quality, for overweight at school entry by weight (syndrome X): relation to reduced fetal 2007, Publ No. 07-E007, pp 1–524. gain during the first 2 years. Arch Pedi-

growth. Diabetologia 1993; 36: 62–67. 11 Horta BL, Bahl R, Martines JC, Victora atr Adolesc Med 2004; 158: 449–452. 5 Symonds ME, Gardner DS: Experimen- CG: Evidence on the Long-Term Effects 15 Baird J, Fisher D, Lucas P, Kleijnen J, tal evidence for early nutritional proof Breastfeeding. Systematic Reviews Roberts H, Law C: Being big or growing gramming of later health in animals. and Meta-Analyses. Geneva, World fast: systematic review of size and

Curr Opin Clin Nutr Metab Care 2006; Health Organization, 2007, pp 1–52. growth in infancy and later obesity.

9: 278–283. 12 Kramer MS, Matush L, Vanilovich I, BMJ 2005; 331: 929–931. 6 Simmons R: Developmental origins of Platt RW, Bogdanovich N, Sevkovskaya 16 Monteiro POA, Victora CG: Rapid adult metabolic disease: concepts and Z, Dzikovich I, Shishko G, Collet JP, growth in infancy and childhood and controversies. Trends Endocrinol Martin RM, Davey Smith G, Gillman obesity in later life – a systematic re-

Metab 2005; 16: 390–394. MW, Chalmers B, Hodnett E, Shapiro view. Obes Rev 2005; 6: 143–154. 7 Schack-Nielsen L, Michaelsen KF: S; PROBIT Study Group: Effects of pro- 17 Ong KK, Loos RJF: Rapid infancy Breast feeding and future health. Curr longed and exclusive breastfeeding on weight gain and subsequent obesity:

Opin Clin Nutr Metab Care 2006; 9: child height, weight, adiposity, and Systematic reviews and hopeful sugges-

289–296. blood pressure at age 6.5 y: evidence tions. Acta Paediatr 2006; 95: 904–908.

70 Pediatric Nutrition in Practice Koletzko B. (ed): Pediatric Nutrition in Practice. Basel, Karger, 2008, pp 71–75

1 General Aspects of Childhood Nutrition

1.6 Food Safety Hildegard Przyrembel

Key Words tablished in 1961 by the Food and Agriculture Food safety ؒ Food hygiene ؒ Residues ؒ Organization of the United Nations (FAO) and Contaminants ؒ Production ؒ Processing ؒ the World Health Organization (WHO), which .Preparation ؒ Storage ؒ Standards ؒ Code of is to be implemented by national legislation practice Numerous scientific bodies consisting of independent experts advise on limits for residues, contaminants, naturally occurring toxins, food Key Messages additives and infectious agents based on toxico- R Nutritional safety of foods for infants and young logical and microbial risk assessment to mini- children can be assessed by clinical studies, while mize the risk of food-borne diseases (details: In- microbial and chemical safety must be defined by risk analysis, regulated by law and monitored by ternational Portal on Food Safety, Animal and controls Plant Health, www.ipfsaph.org). R Young and immature infants are particularly sus- Food-borne diseases are caused by agents that ceptible to microbial and chemical hazards from enter the body through the ingestion of food and food are a growing public health problem. Food- and R Safe water, both chemically and microbially, is needed for the preparation of food for infants and water-borne diarrheal diseases kill approximate- young children in particular ly 1.8 million people annually, most of whom are R Safe food products can become unsafe in the children. In industrialized countries the percent- course of inappropriate handling, preparation and age of people suffering from food-borne diseases storage Copyright © 2008 S. Karger AG, Basel each year has been reported to be up to 30%. They are caused by naturally occurring toxins such as mycotoxins, persistent organic pollutants such as dioxins and polychlorinated biphenyls (PCBs), heavy metals such as lead, cadmium and mercu- Introduction ry, and by microorganisms such as salmonella, campylobacter, etc. While nutritional safety is the outcome tested in However, the production of safe foods, by appropriate clinical studies by nutrition science ensuring plant and animal health, by applying [1] , chemical and microbial safety of food is not Hazard Analysis and Critical Control Point tested in humans but is the object of regulations, (HACCP) principles and observing hygiene [2] , standards and codes of practice developed on a must be complemented by appropriate and hy- global basis, e.g. by the Codex Alimentarius es- gienic handling of food by consumers. R e s i d u e s Committee on Food Additives and Contami- nants and the European Food Safety Authority Residues in foods derive from deliberately ap- have defined provisional tolerable weekly intake plied substances, food additives, pesticides and levels (table 1 ). veterinary drugs. For these substances maximal Nitrate, which is accumulated by some plants residue levels (MRLs) based on good practice (i.e. and can occur in water wells, is considered a con- application at levels to achieve the desired effect taminant, and maximum levels have been set for but not higher) are defined. MRLs must be com- ready-to-eat vegetable meals for infants. Nitrate, patible with the acceptable daily intake (ADI) itself not very toxic, is partially converted into ni- levels, which are the amounts of a chemical that trite, which can form carcinogenic nitrosamines can be ingested daily over a lifetime without pro- with secondary amines from food, which in turn ducing appreciable health risks. They do not ap- can induce methemoglobinemia in young infants ply to infants below 3 months of age. Because in- at intakes of 17 mg nitrate/kg per day, particu- fants and young children have food patterns with larly in infants with still high levels of fetal hemo- less variety than adults and consume more food globin and/or concomitant gastrointestinal or per unit of body weight, lower MRLs are required urinary tract infection. Home-prepared meals for some pesticides in foods for infants and young containing vegetables potentially high in nitrate children [3] , meaning, for example in the Euro- (radish, beetroot, fennel, lettuce, kohlrabi, spin- pean Community, the use of certain pesticides on ach) should therefore not be stored and re- crops intended for infants and young children is warmed. forbidden [4] . On an international level, residue Heavy metals, particularly methylmercury in levels are to be ‘reduced to the maximum extent seafood products, cadmium taken up from the possible’ for example in infant formula and ce- soil by plants, and lead mostly deriving from in- real-based foods for infants and young children dustrial waste in plants and via feed in animal [5] . food, are of particular concern for children because of their long half-life and because of neurobehavioral, neurotoxic and nephrotoxic ad- Contaminants verse effects, respectively. Organohalogen compounds, e.g. dioxins and Contaminants from the environment in food are PCBs, accumulate and persist for many years in unintended and often unavoidable, e.g. dioxins, body fat. They have adverse effects on develop- PCBs and heavy metals, or are introduced during ment, reproduction, the immune and endocrine processing. Naturally occurring contaminants systems. Both for heavy metals and organohalo- are fungal mycotoxins, particularly in cereals, gen compounds, maximum levels in food are rec- nuts and fruit juices. They are quite stable to nor- ommended by the Codex Alimentarius, e.g. for mal cooking temperatures and toxic to the liver lead [7] and contaminants in general [8] . and/or the kidney, and some are carcinogenic in rodents. Maximum levels for different mycotoxins in various categories of food and animal feed Food Toxicology have been set worldwide in the majority of countries [6] . Because it is impossible to completely The risk assessment of compounds used deliber- eliminate mycotoxins in food and feed, until 1997 ately in the production of foods differs from that the aim was to have the mycotoxin levels as low of contaminants, but the process is similar. In the as reasonably achievable. Both the Joint Expert first case ADIs are based on identified ‘no ob-

72 Pediatric Nutrition in Practice Table 1. Toxicological data on some relevant contaminants in food

Substance Most recent Species Relevant endpoint LOAEL PTWI assessment per kg body per kg body weight per day weight per week

Methylmercury JECFA, 2003 human neurobehavioral 1.6 ␮g NRC, 2000 children development 0.7 ␮g Lead JECFA, 2000 human neurotoxicity 25 ␮g Cadmium JECFA, 2003 pig renal toxicity 7 ␮g Dioxins and SCF, 2000/2001 rat development, 14 pg WHO-TEQ dioxin-like PCB reproduction Ochratoxin A JECFA, 2001; pig renal toxicity 8 ␮g 100 ng 1 EFSA, 2006 8 ␮g 120 ng

LOAEL = Lowest observed adverse effect level; PTWI = provisional tolerable weekly intake; PCB = polychlorinated biphenyl; JECFA = Joint Expert Committee on Food Additives and Contaminants (FAO); NCR = National Research Council (USA); SCF = Scientific Committee on Food of the European Commission; EFSA = European Food Safety Authority; TEQ = Toxicity equivalent.

served adverse effect levels’ (NOAELs) from the Short-term intakes of a residue/contaminant most sensitive study in the most sensitive species, in excess of ADI/TDI do not necessarily mean and by dividing the NOAELs by a safety factor that adverse health effects will follow. However, (most often of 100) to account for interspecies children may be particularly susceptible, and the and intraspecies variability in sensitivity. Safety expected lifespan and, therefore, the available factors can be modified according to the quantity time for the manifestation of adverse effects in a and quality of available data and by taking the young person are longer. Table 1 lists toxicologi- severity or irreversibility of an effect into ac- cal data on some important contaminants. count. The result of the same procedure applied to contaminants is a tolerable daily intake (TDI) or, in the case of contaminants with long half- Infectious Food-Borne Diseases lives, a tolerable weekly intake, sometimes a pro- visionally tolerable weekly intake. Dividing the Microbial contamination of food can occur NOAELs by the actual exposure of consumers throughout the chain of food production, pro- permits an estimation of the margin of safety. cessing and storage. Microbial diseases which Compounds with genotoxic and/or carcino- can be transferred from animals to man are zoo- genic activity have presumably no threshold for noses, the most important agents being salmo- effects. Instead the margin of exposure can be es- nella, mycobacteria, brucella, campylobacter, lis- timated, that is, the ratio between a defined point teria, toxoplasma, yersinia and parasites like on the dose-response curve in the animal carci- trichinella and echinococcus. nogenicity study and the human intake. A mar- Food-borne viral illnesses, e.g. noroviruses gin of exposure of 10,000 or higher is considered and hepatitis A, are on the increase. They relate to be of low health concern [9] . predominantly to fresh products rather than to industrially produced foods, and/or are linked to

Food Safety 73 Table 2. Recommendations for safe handling, prepara- I n f a n t F o r m u l a tion and storage of foods

– Wash hands before preparing and feeding Feeding breast milk substitutes requires the avail- – Wash hands after going to toilet ability of clean and safe water and cooking facili- – Use safe water or treat it to make it safe ties [11] . – Wash and clean surfaces and equipment used for A typical example of the importance of food preparation HACCP principles in the production of foods, – Use clean utensils to prepare and serve food – Wash fruits and vegetables, especially if eaten raw and sanitary measures to be applied by the con- – Separate raw and cooked food and use separate sumer, is the case of Enterobacter sakazakii in utensils for preparing them powdered infant formula. This microorganism – Cook fresh, unpasteurized milk has caused outbreaks of sepsis, meningitis or nec- – Cook food thoroughly, particularly meat, poultry, rotizing enterocolitis, especially in premature in- eggs and seafood (internal temperature at least 70° C – Serve foods immediately after preparation fants and those less than 2 months old. Although – Keep cooked food hot (>60° C) prior to serving the overall incidence seems to be low, mortality – Do not leave cooked food for more than 2 h at room rates between 20 and 50% have been reported. temperature – Discard uneaten prepared food or refrigerate Powdered infant formula is not sterile, and even

(preferably <5° C) when manufactured under strict hygiene, the oc- – Refrigerate all cooked and perishable food currence of low counts (1–3/g) of coliform bacte- immediately (preferably <5° C) ria cannot be prevented. E. sakazakii does not – Store raw and cooked food in separate containers grow in the dry powder but starts to replicate af- – Store food preferably dry – Do not store food too long (even in refrigerator) ter preparation with water and at temperatures 1 1 – Do not use beyond expiry date 5 ° C. It ca n be dest royed by temperat u res 60 ° C. – Do not thaw frozen food at room temperature Measures to reduce the risk of infection include – Heat stored prepared food thoroughly (>70° C) preparation in a sterile environment with boiled 1 water ( 70 ° C), feeding immediately after appropriate cooling, limiting of feeding duration and infusion via feeding tubes at room temperature to less than 4 h, and discarding uneaten residues contamination of food by an infected food han- [12] . dler. The impact of infectious diseases on mortality of children under five is more than two times C o n c l u s i o n s greater in malnourished children. Apart from attempts to improve both the quality and quantity • Practical recommendations for the safe han- of food, continued frequent breastfeeding or, if dling of food at home and elsewhere are given possible, re-lactation are important measures in table 2 [10] to minimize the risk from pathogens in foods • Toxicological safety of food is primarily the or fluids and to profit from the protective factors responsibility of the manufacturer provided by breast milk. • Microbial safety of food is both the responsibility of the manufacturer and the person preparing and serving it

74 Pediatric Nutrition in Practice References

1 Aggett PJ, Agostoni C, Goulet O, et al: 4 Commission Directive 2006/141/EC of 9 Larsen JC: Risk assessment of chemi- The nutritional and safety assessment 22 December 2006 on Infant Formulae cals in European traditional foods.

of breast milk substitutes and other and Follow-On Formulae and Amend- Trends Food Sci Technol 2006; 17: 471– dietary products for infants: a com- ing Directive 1999/21/EC. Offic J Eur 481. mentary by the ESPGHAN Committee Union 30.12.2006:L 401/1–33. 10 World Health Organization: Guiding on Nutrition. J Pediatr Gastroenterol 5 FAO/WHO: Standard for Infant For- Principles for Feeding Infants and

Nutr 2001; 32: 256–258. mula and Formulas for Special Medical Young Children during Emergencies. 2 FAO: Food Quality and Safety Purposes Intended for Infants. Codex- Geneva, WHO, 2004. Systems – A Training Manual on Food Stan 72 – 1981. Revision 2007. 11 Howard G, Bartram L: Domestic Water Hygiene and the Hazard Analysis and 6 FAO Food and Nutrition Papers – 81: Quantity, Service Level and Health. Critical Control Point (HACCP) Sys- Worldwide Regulations for Mycotoxins Geneva, WHO, 2003. WHO/SDE/ tem. Rome, FAO, 1998. http://www.fao. in Food and Feed 2003. FAO Corporate WSH/3.02. org/docrep/W8088E/W8088E00.htm. Document Repository 2004, http:// 12 FAO/WHO: Enterobacter sakazakii 1 3 Schilter B, Renwick AG, Huggett AC: www.fao.org/docrep/007/y5499e/ and Other Microorganisms in Pow- Limits for pesticide residues in infant y5499e04.htm. dered Infant Formula. Rome/Geneva, foods: a safety-based approach. Regul 7 FAO/WHO: Codex Standard Maximum FAO/WHO, 2004. http://www.who.int/

Toxicol Pharmacol 1996; 24: 126–140. Levels for Lead. CODEX STAN 230– foodsafety/publications/micro/es.pdf. 2001, (Rev. 1–2003). 8 FAO/WHO: Codex Standard for Con- taminants and Toxins in Food. CODEX STAN 193–1995 (Rev. 1–1997).

Food Safety 75 Koletzko B. (ed): Pediatric Nutrition in Practice. Basel, Karger, 2008, pp 76–79

1 General Aspects of Childhood Nutrition

1.7 Gastrointestinal Development, Nutrient Digestion and Absorption Michael J. Lentze

Key Words The GI tract has digestive, absorptive, secretory and barrier functions. In addition, it is part Nutrient digestion ؒ Absorption ؒ Fetal intestinal development ؒ Motility of the endocrine organ and the immunological system. The interaction between various organs and the complex structure and function of the GI Key Messages tract develops during fetal life in order to provide R The fetal human gut is prepared for the digestion the newborn baby with a functional GI system to and absorption of nutrients already at the 24th survive in the external world. This includes the week of gestation digestion and absorption of nutrients, transport R Macronutrients, given even to premature babies, through the gut as well as a barrier function to a can be digested and absorbed R The rate-limiting factor during fetal life, particular- large number of microbiota and the symbiotic life ly for premature infants, is the development of mo- with them. Antigens need to be identified and tility Copyright © 2008 S. Karger AG, Basel taken care of without involving the whole body in an illness. The human gut is formed from the endoder- mal layer of the embryo by incorporation of the dorsal part of the yolk sac during the infolding of Introduction the embryonic disc. At the 4th week of gestation the first tube has a length of 4 mm from the The development of the gastrointestinal (GI) mouth to cloaca. During pregnancy it elongates tract during intrauterine life for a human fetus is about 1,000-fold until full-term. The stomach at the prerequisite for survival in external life. The term has a volume of about 30 ml, the small intes- digestive and absorptive capacity of the intestinal tine a length of 250–300 cm, the large intestine a organs as well as the contact of foreign pathogens length of 30–40 cm. Between the 9th week of ges- with an active immune system guarantee the tation and birth the small intestine undergoes ex- normal growth and wellbeing of an infant in ear- traordinary changes from a primitive stratified ly life. As the number of premature babies below epithelium of undifferentiated epithelial cells 1,000 g is increasing, knowledge of the digestive into a fully differentiated organ with villi and and absorptive functions of the GI tract becomes crypts [1] . The formation of Peyer’s patches starts of vital interest for neonatologists feeding these at 16–18 weeks of gestation when the first lym- very low birthweight (VLBW) infants. phocytes are seen in the lamina propria [2] . SGLT-1, GLUT-5

Lactase

Maltase-glucoamylase

Sucrase-isomaltase

0510 15 20 2530 35 40 1 Weeks of gestation

Prematures <1,500 g BBM peptidases

Amino acid transporters

Peptide transporters

Detection of ﬁrst activity Full activity

Fig. 1. Development of brush border enzymes and transporters during fetal life.

Parallel to the morphological changes during formula. However, the overall lactase activity fetal development the digestive and absorptive along the small intestine even in VLBW infants functions of the GI tract begin to appear at the is sufficient for hydrolyzing lactose into glucose 10th week of gestation and fully express their ac- and galactose. tivities between the 26th week of gestation and The transport system responsible for the up- term or within the first month of life. take of glucose and galactose, the sodium-depen- The brush border enzymes, lactase, maltase- dent glucose transporter-1 (SGLT-1) is fully ac- glucoamylase and sucrase-isomaltase, are first tive already by the 25th week of gestation as is determined at the 10th week of gestation ( fig. 1 ). glucose transporter-5 (GLUT-5) [5] . For the di- Sucrase-isomaltase reaches its full activity al- gestion of proteins the pancreatic enzymes, tryp- ready by the 25th week of gestation, whereas lac- sin, chymotrypsin and carboxypeptidase, are tase activity is fully developed by the 32nd week first detected in the 24th week of gestation (fig. 2). of gestation [3, 4] . As lactose is the predominant Full activity is reached by the 26th week of gesta- sugar in breast milk, the possibility exists that tion. Trypsinogen is activated by enterokinase in premature babies born before the 32nd week of the 24th week of gestation. The brush border pep- gestation might lack full lactase activity when fed tidases, the amino acid transporters as well as breast milk or a lactose-containing premature peptide transporters start their transport activi-

Gastrointestinal Development, Nutrient Digestion and Absorption 77 Breast milk: Bile salt-stimulated lipase

Trypsinogen Trypsin

Gastric lipase Pancreatic lipase

20 22 24 26 28 30 32 40 6 Weeks of gestation Months Enterokinase Amylase

Detection of ﬁrst activity Prematures Full activity <1,500 g

Fig. 2. Development of pancreatic enzymes, gastric lipase and enterokinase during fetal life.

ties by the 10th week of gestation and reach full drolyzed by the action of sucrase-isomaltase and activity by the 25th week of gestation [6] . The di- maltase-glucoamylase [8] . gestion of proteins and the absorption of amino Although the digestive and absorptive capac- acids and dipeptides are effective already for ity of the GI tract is well prepared for external life VLBW infants. Fat digestion depends on various after birth even for premature babies, immature lipases and the formation of micelles. The activi- motility is the limiting system particularly for ties of the responsible lipases, gastric and pancre- premature infants to cope with external feeding. atic lipases, are first measurable by the 24th week Here, the response of the intestine to a bolus feed of gestation. Full enzyme activity develops steadi- depends on the maturity of the gut. In small in- ly towards term and after birth. In the breastfed fants before 31 weeks of post-conceptional age, infant, breast milk lipase (bile salt-stimulated li- who are usually receiving low volumes of contin- pase) enhances fat digestion during the first uous enteral feed, ordinary postprandial activity weeks of life [7] . The digestion of starch is the last does not occur [9] . Between 31 and 35 weeks post- to develop during pregnancy and after birth. conceptional age, postprandial activity is in- Pancreatic amylase is first detected in the 22nd duced in infants by giving them larger volumes of week of gestation, but reaches its full activity as feed. However, the activity remains in a fasting late as the 6th month after birth. Premature or pattern with a superimposed more random post- term infants cannot easily digest large amounts prandial activity. Finally, in infants over 35 weeks of starch. Small amounts of starch can be given to post-conceptional age, who receive large volumes premature and term infants without difficulty of bolus feed, there is a disruption of the cyclical because amylose and amylopectin are also hy- fasting activity and replacement with continuous

78 Pediatric Nutrition in Practice activity. Whether this motility pattern can be adis still not very active. Premature formulas or for- vanced by pharmacological measures, such as the tified breast milk can be applied to VLBW in- administration of cortisol, remains to be seen [10, fants or extremely VLBW infants in small quan- 11] . tities. From the 31st week onwards the quantity of enteral feeds becomes less of a problem. As far as macronutrients are concerned, protein is well di- C o n c l u s i o n s gested and absorbed. Lactose is also well digested and absorbed, but starch can only be digested in The feeding of premature infants below 35 weeks small quantities. The digestion of fat increases of gestation requires knowledge of the physiolog- quickly from the 26th week of gestation and can ical functions at this time. Whereas digestive and be enhanced by the administration of breast milk 1 absorptive functions are mostly developed from which provides bile salt-stimulated lipase. the 24th week post-conceptional age, GI motility

References

1 Moxey PC, Trier JS: Development of vil- 5 Davidson NO, Hausman AM, Ifkovits 8 Terada T, Nakanuma Y: Expression of lous absorptive cells in the human fetal CA, et al: Human intestinal glucose pancreatic enzymes (alpha-amylase, small intestine: a morphological and transporter expression and localization trypsinogen, and lipase) during human

morphometric study. Anat Rec 1979; of GLUT5. Am J Physiol 1992; 262: liver development and maturation.

195: 463–482. C795–C800. Gastroenterology 1995; 108: 1236–1245. 2 Owen WL, Jone AL: Epithelial cell spe- 6 Adibi SA: Regulation of expression of 9 Bisset WM, Watt J, Rivers RP, Milla PJ: cialisation within human Peyer’s the intestinal oligopeptide transporter Postprandial motor response of the patches: an ultrastructural study of (Pept-1) in health and disease. Am J small intestine to enteral feeds in pre-

intestinal lymphoid follicles. Gastroen- Physiol Gastrointest Liver Physiol 2003; term infants. Arch Dis Child 1989; 64:

terology 1974; 66: 189–203. 285:G779–G788. 1356–1361. 3 Lentze MJ: Die Ernährung von Frühge- 7 Boehm G, Bierbach U, Senger H, et al: 10 Bisset WM, Watt JB, Rivers RP, Milla borenen unter 1500 g – enterale Activities of lipase and trypsin in duo- PJ: Ontogeny of fasting small intestinal Voraussetzungen. Monatsschr Kinder- denal juice of infants small for gesta- motor activity in the human infant.

heilk 1986; 134: 502–507. tional age. J Pediatr Gastroenterol Nutr Gut 1988; 29: 483–488.

4 Menard D: Development of human in- 1991; 12: 324–327. 11 Bisset WM, Watt JB, Rivers RP, Milla testinal and gastric enzymes. Acta Pae- PJ: Measurement of small-intestinal

diatr Suppl 1994; 405: 1–6. motor activity in the preterm infant. J

Biomed Eng 1988; 10: 155–158.

Gastrointestinal Development, Nutrient Digestion and Absorption 79 Koletzko B. (ed): Pediatric Nutrition in Practice. Basel, Karger, 2008, pp 80–84

1 General Aspects of Childhood Nutrition

1.8 Gut Microbiota in Infants Seppo Salminen ؒ Mimi Tang

Key Words er’s microbiota, mode of delivery and birth envi- M i c r o b i o t a ؒ Probiotics ؒ Prebiotics ؒ Health ronment [1, 2] . The microbiota of the mother is determined by genetic and environmental factors. Stress and dietary habits during later preg- K e y M e s s a g e s nancy have a significant impact on the microbio- R A healthy microbiota preserves and promotes host ta at delivery, thus influencing the quality and wellbeing and absence of disease, especially in the quantity of first colonizers of the newborn. Sub- gastrointestinal tract sequently, feeding practices (formula or breast- R Initial colonization with ‘pioneer bacteria’ is en- fed) and the infant’s home environment influ- hanced by both bacteria and galacto-oligosac- ence the succession microbiota at the genus and charides in breast milk and the microbiota of the mother. These pioneer bacteria direct the later mi- species level, as well as species composition and crobiota succession which forms the platform for a numbers of bacteria. healthy gut microbiota throughout one’s lifetime R The microbiota resembles that of adults by 1–2 Succession of Microbial Communities years of age The establishment of microbiota in the newborn R Bifidobacterial numbers in children often remain higher than in adults occurs in a stepwise fashion. Studies in mice have R A disturbed microbiota succession during early in- shown that the first bacteria to colonize the new- fancy has been linked to an increased risk of devel- born intestine (‘pioneer bacteria’) can modulate oping infectious, inflammatory and allergic diseas- gene expression in host intestinal epithelial cells. es later in life This results in an altered intestinal microenvi- R Intestinal microbial colonization and its modula- ronment which influences the nature of subse- tion through dietary means are important considerations during the first years of life quent intestinal colonization. Copyright © 2008 S. Karger AG, Basel In the newborn, initial colonization with fac- ultative anaerobes, enterobacteria, coliforms, lactobacilli and streptococci is rapidly followed by colonization with anaerobic genera such as Bi- Initial Establishment of Microbiota fidobacterium, Bacteroides, Clostridium, and lactic acid bacteria. Molecular analyses demonstrate Source of Original Microbiota significant differences in the microbiota of for- The microbiota of a newborn is acquired from mula-fed and breastfed infants with respect to bi- the mother at birth and develops rapidly thereaf- fidobacterial numbers and species composition. ter. It is initially strongly dependent on the moth- In breastfed infants, bifidobacteria constitute from 60 to 90% of the total fecal microbiota, while 6-month-old infants reported higher bifidobac- lactobacilli comprise less than 1% [3] . The most terial levels and lower clostridial numbers in common bifidobacterial species in breastfed in- breastfed infants than infants receiving either fants are B. breve, B. infantis and B. longue [4] . In formula or formula with prebiotics. Ongoing im- formula-fed infants the microbiota is more com- provements in formulae have lessened these dif- plex and influenced by the formula composition. ferences [5] . The lactic acid bacteria composition in breastfed The healthy intestinal microbiota in infancy is and formula-fed infants is similar, with Lactoba- characterized by a large gram-positive bacterial cillus acidophilus group microorganisms such as population and significant numbers of bifido- L. acidophilus , L. gasseri and L. johnsonii being bacteria, mainly B. longum, B. breve and B. infan- most common. Microbiota differences between tis. Lactic acid bacteria may play a role in provid- 1 breastfed and formula-fed infants have lessened ing the right intestinal environment for bifi- with improved infant formulas. dobacteria to dominate. A healthy microbiota during infancy is particularly important as this establishes the basis for healthy gut microbiota Gut Microbiota in the First 6 Months of Life later in life.

Breastfeeding for 4–6 months may assist in the development of healthy gut microbiota by pro- Gut Microbiota in Infants from 6 Months viding bifidobacteria and lactic acid bacteria Onwards which reinforce colonization, and by supplying galacto-oligosaccharides that promote a healthy After the first 6 months of life, the microbiota be- microbiota composition. Breastfeeding also facil- comes more diverse [6] . Several studies have ex- itates the exchange of microbes between mother amined the progression of microbiota from 6–24 and infant via skin contact and exposure to mi- months of life (summarized in fig. 1). Weaning is crobiota in the immediate environment. Every associated with increased Escherichia coli, en- individual has a unique characteristic microbiota terococci, bacteriodes and anaerobic gram-posi- during later phases of breastfeeding that com- tive cocci and decreased enterobacteria. Differ- prises a dynamic mixture of microbes typical to ences between breastfed and formula-fed infants each individual. Weaning, introduction of solid disappear. foods, and antimicrobial drug treatment will By 1–2 years of age the microbiota resembles break the constant supply of oligosaccharides that of adults, although levels of bifidobacteria and microbes from the mother, thus affecting in- and enterobacteria in children (16 months to 7 testinal microbiota development. years) remain higher than in adults. Molecular analysis of bacterial communities in healthy babies during the first 10 months of life demonstrated progression from a simple profile The Importance of a Healthy Microbiota: in the first days of life to a more complex diverse Biological Effects profile with members of the genera Bifidobacte- rium, Ruminococcus, Enterococcus, Clostridium, The intestinal microbiota is crucial for normal and Enterobacter identified by 6 months of age development of the gut-associated lymphoid tis- [3] . Bifidobacterium and Ruminococcus species sue (GALT), and has important effects on intes- dominated the intestinal microbiota with high tinal mucosal barrier function and other aspects level stable expression over time. A pilot study in of intestinal function.

Gut Microbiota in Infants 81 Unculturables

Bacteroides Others Bifidobacteria

Coliforms Clostridia

Fig. 1. Relative changes in gut mi- Lactobacilli crobiota composition suggested by culture-dependent and culture-in- Microbial concentration (relative to total) to (relative Microbial concentration dependent studies. The numbers of 0 months 6 months 24 months Adults bifidobacteria can be influenced by Age diet, probiotics and prebiotics.

Immune Development ing the host with an anti-inflammatory stimulus Microbial colonization of the newborn intestine and directing the host–microbe interaction to- is required for normal immune development, wards immune tolerance. In particular, the bi- which in turn is important for regulation of gut fidobacteria-dominated environment in child- inflammatory responses and oral tolerance in- hood may provide a more anti-inflammatory duction. The mucosal immune system of the gas- stimulus than bacteria from adults which have trointestinal tract is constantly challenged by been shown to be more proinf lammatory. A com- diverse antigens including microbial and food plex microbial community is required to achieve antigens. Such priming of the gut-associated lym- a healthy microbiota that exhibits powerful anti- phoid tissue is important for two opposing func- pathogenic and anti-inflammatory capabilities. tions: mounting a response to pathogens and maintaining hyporesponsiveness to innocuous Intestinal Function antigens. Mice raised in a germ-free environment An absent or inadequate intestinal microbiota fail to develop oral tolerance and have a persistent has been shown to cause defects in intestinal bar- Th2-dependent antibody response [7] . This im- rier function. The microbiota may also influence mune deviation can be corrected by reconstitu- other intestinal functions. Before weaning, for- tion of intestinal microbiota, but only if this oc- mula-fed infants have a greater ability to ferment curs during the neonatal period [7] . complex carbohydrates than breastfed infants, An important question is how the microbiota probably due to the presence of a more complex is altered by the significant changes in diet dur- microbiota. Following weaning these differences ing the first years of life and how this impacts disappear. Breastfed infants have delayed estab- upon intestinal immune development. The host– lishment of mucin-degrading microbiota, but microbe cross-talk during and after breastfeed- this increases in both groups between 6 and ing is critical in this regard. The strains of healthy 9 months. Conversion of cholesterol to coprosta- gut microbiota are likely to stimulate local and nol commences after 6 months of age, and lev- systemic immune responses via pattern recogni- els of ammonia, phenol, ␤-glucosidase and ␤ - tion molecules such as toll-like receptors provid- glucuronidase activity increase after weaning.

82 Pediatric Nutrition in Practice ␤ -Glucuronidase activity is often higher in for- of probiotics, the timing of probiotic administra- mula-fed infants; however, this difference re- tion may also be important. For example, in sepa- solves after weaning. rate studies, LGG (alone or in combination with other probiotics and a prebiotic) and L. reuteri administered prenatally to mothers in the last 2–4 Maintenance and Modulation of the weeks of pregnancy and to the infant in the first 6 Individually Optimized Healthy Microbiota months of life have been reported to reduce the risk of developing eczema in childhood up to age The healthy gut microbiota created during early 7 years [12–15] . In contrast, a bacterium that had life must be maintained throughout life. Devia- not been characterised in preclinical studies, L. tions in microbiota associated with disease can be acidophilus LAVRI-A1, administered only to in- 1 redirected to the healthy balance by dietary means, fants from 4 weeks to 6 months of life did not have for instance by using probiotics or prebiotics. Pro- any effect on eczema risk, suggesting that prena- biotics are defined as viable microbes which tal administration may be requisite for efficacy in through oral administration produce health ben- the prevention of allergic disease [16]. These re- efits to the host. Probiotics are members of the sults highlight the different effects of specific pro- healthy gut microbiota that mimic the healthy mi- biotics, which are further supported by genomic crobiota of both a breastfed infant and the healthy studies. infant, and are generally regarded as safe [8, 9]. Interestingly, a recent study of LGG adminis- Prebiotics are oligosaccharides that promote ex- tered prenatally to mothers from 36 weeks gesta- pansion of specific microbes with potential to tion and to infants for the first 6 months of life maintain health. A prerequisite for the efficacy of conducted in Germany failed to demonstrate a prebiotics is that such strains are already present protective effect against the development of al- in the gut. Carefully designed combinations of lergic disease [17]. This may reflect reduced pow- probiotics and prebiotics may offer an optimal er of the study (study population 94 as compared means for creating and maintaining a healthy mi- to 159 in the original Kalliomaki et al. study [12]), crobiota, as this would mimic the mother–infant or geographic/population specific differences. relationship of offering both microbes and oligo- Similarly, prebiotic oligosaccharides have saccharides to the newborn infant. different microbiota-modifying properties. Al- It is important to recognize that individual though, most prebiotic components have been probiotic bacterial strains can have distinct and shown to enhance the bifidobacterial microbiota, specific effects [9] . Therefore, the effects of one detailed investigation of specific effects is re- probiotic strain cannot be generalized to another, quired. A wide variety of galacto-oligosaccha- and the individual properties of a probiotic strain rides are found in breast milk, and have docu- must be evaluated prior to clinical application. mented bifidogenic and health-promoting effects For example, in a double-blind placebo-controlled in the infant gut. However, some fructo-oligosac- trial, Lactobacillus rhamnosus GG (LGG) but not charides have been reported to enhance levels of a mixture of 4 probiotic strains (LGG, L. ramno- unknown microbes in the human gut, thus po- sus LC705, B. breve Bbi99, Propionibacterium JS) tentially facilitating untoward effects in infants. was effective for the treatment of eczema [10] . Therefore, when evaluating a probiotic or prebi- LGG has also been shown to enhance IgA re- otic for clinical use, the safety and clinical benefit sponses against rotavirus, which is not found with of that specific product must be documented to different strains of the same species [11] . Further- verify efficacy before it can be recommended for more, in addition to species/strain specific effects clinical application.

Gut Microbiota in Infants 83 Conclusions promoting the bifidogenic environment through prebiotic galacto-oligosaccharides • The healthy human microbiota is metaboli- and microbes in breast milk and introducing cally active and provides an important defense environmental bacteria through contact with mechanism for the host. Deviations in its the infant composition are related to multiple disease • Both the succession of microbial communities states during the first years of life and the sequelae • Evidence supports a crucial role for the infant of these events need to be clarified in more de- microbiota and the first colonization steps in tail later health. Bifidobacteria play a key role in • The potential application of specific probiot- this process ics and/or prebiotics to influence microbiota • The mother–infant contact has an important development for the treatment and prevention impact on initial microbiota development, of disease also warrants further evaluation providing the critical first inoculum at birth,

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6 Mikelsaar M, Mändar R, Sepp E, food development. Br J Nutr 1998; otics for primary prevention: No clini- Annuk H: Human lactic acid microflo- 80(suppl):147–171. cal effects of Lactobacillus GG ra and its role in the welfare of the host; 12 Kalliomäki M, Salminen S, Arvilommi supplementation. Pediatrics 2008;121: in Salminen S, von Wright A, Ouwe- H, et al: Probiotics in primary preven- e850–e858. hand A (eds): Lactic Acid Bacteria. New tion of atopic disease: a randomised

York, Dekker, 2004, pp 453–506. placebo-controlled trial. Lancet 2001;

357: 1076–1079. 13 Kalliomäki M, Salminen S, Poussa T, et al: Probiotics and prevention of atopic disease: 4-year follow-up of a randomised placebo-controlled trial.

Lancet 2003; 361: 1869–1871.

84 Pediatric Nutrition in Practice Koletzko B. (ed): Pediatric Nutrition in Practice. Basel, Karger, 2008, pp 85–89

2 Nutrition of Healthy Infants, Children and Adolescents

2.1 Breastfeeding Kim Fleischer Michaelsen

Key Words Nutrients and Other Substances in Human Milk Breastfeeding ؒ Human milk ؒ Lactation ؒ Baby friendly hospital initiative ؒ HIV, mother-to-child transmission Human milk has about the same energy content as cow’s milk (about 670 kcal/l), while many important nutrients, such as protein, sodium, po- Key Messages tassium, magnesium and zinc, are present at 2 R Breastfeeding provides optimal nutrition for in- much lower contents, typically one third to half fants of the content found in cow’s milk ( table 1 ). This R An infant should preferably be exclusively breast- is a reflection of the much slower growth velocity fed for about 6 months and should continue breast- in humans, and thereby the lower need of nutri- feeding up to the age of 12 months or beyond Copyright © 2008 S. Karger AG, Basel ents important for growth. Human milk also contains many other substances apart from nutrients. These include hormones, growth factors, and immune-related compounds, such as anti- Introduction bodies (sIgA), leukocytes (B and T lymphocytes, neutrophils and macrophages), oligosaccharides, Breastfeeding provides optimal nutrition for the nucleotides and cytokines. It is likely that many infant and also has many non-nutritional bene- of these non-nutritional substances are involved fits for the child and mother. Therefore, it has in many of the short- and long-term effects been recommended by WHO and many coun- breastfeeding has on the infant. tries that one should aim for exclusive breastfeeding of infants for about 6 months and for continued breastfeeding up to the age of 12 months or Positive Effects on the Infant and Mother beyond. In populations with high rates of infectious diseases breastfeeding during the 2nd year Breastfeeding has significant positive effects on of life or longer has been shown to reduce mor- health and development during infancy, later bidity and mortality. There is a considerable in- during childhood and most likely also some ef- terest in the public health aspects of breastfeed- fects during adulthood [2–4] . However, as most ing and an increasing number of scientific stud- studies are observational, confounding is diffi- ies exploring the mechanisms behind the numer- cult to rule out, e.g. mothers who choose to ous benefits of breastfeeding [1] . breastfeed in industrialized countries are typi- Table 1. Mean macronutrient and energy contents in mature human milk and in cow’s milk

Component Mature human milk % of Cow’s milk % of (≥14 days) energy energy

Protein 1.0 g/100 g 6 3.4 g/100 g 21 of which caseins 0.4 g/100 g (40% of protein) 2.4 2.8 g/100 g (80% of protein) 17 Fat 3.8 g/100 g 52 3.7 g/100 g 51 Lactose 7.0 g/100 g 42 4.6 g/100 g 28 Minerals 0.2 g/100 g – 0.8 g/100 g – Energy 66 kcal/100 g 100 65 kcal/100 g 100

Adapted from Koletzko [10].

cally better educated and their children also have of life and are leaner and slightly shorter than a lower risk of developing some diseases. formula-fed infants at the age of 12 months [6] . The most evident effect of breastfeeding is This was the main reason why the WHO devel- protection against infectious diseases, especially oped a new global growth standard based on against diarrhea and respiratory tract infections. breastfed infants (see Chapters 1.1 and 4.2). It has In developing countries mortality during the been suggested that the different growth pat- first years of life is considerably higher among terns could be a reason why breastfed infants those not being breastfed [5] . But also in indus- seem to have a lower risk of some non-commu- trialized countries the risk of infectious diseases, nicable diseases, including obesity, later in life especially diarrhea, is significantly less among (see Chapter 1.5). those being breastfed. These differences could be Breastfeeding is also relevant for maternal explained by passive protection of mucous mem- physiology and health. From a global perspective branes provided by the antibodies and other im- the most important effect is the inhibitory effect mune components in human milk, but there is on ovulation, lactational amenorrhea, which in also evidence that the child’s own immune sys- populations with low use of contraceptives en- tem is influenced by breastfeeding. This could be hances child spacing, and thereby has a positive the reason that some immune-related diseases, effect on infant and young child health. More- e.g. asthma, type-1 diabetes, inflammatory bow- over, breastfeeding induces utilization of mater- el diseases and some childhood cancers, are less nal body fat stores and can thus help to decrease common among breastfed children compared excessive body fat depots, and it reduces the ma- with children who had been predominantly for- ternal risk for later development of type-2 diabe- mula-fed as infants. A consistent finding in many tes, breast and ovarian cancer. studies from both industrial and developing countries is a small but significant advantage of breastfeeding on later cognitive function. This Potential Untoward Effects of Breastfeeding effect is likely to be related to an optimal ratio between n-3 and n-6 fatty acids and the content Transmission of HIV of the long-chain polyunsaturated fatty acid Breastfeeding can cause mother-to-child trans- docosahexaenoic acid in human milk. Breast- mission of HIV. However, in countries with a feeding has also an effect on growth. Breastfed high prevalence of infectious diseases, especially infants gain weight faster during the first months diarrhea, early cessation of breastfeeding may re-

86 Pediatric Nutrition in Practice Table 2. Breastfeeding and mother’s medication

Breastfeeding contraindicated Anticancer drugs (antimetabolites); Radioactive substances (stop breastfeeding temporarily) Continue breastfeeding Side effects possible Selected psychiatric drugs and anticonvulsants (see individual drug) Monitor baby for drowsiness Use alternative drug if possible Chloramphenicol, tetracyclines, metronidazole, quinolone antibiotics (e.g. ciprofloxacin) Monitor baby for jaundice Sulfonamides, dapsone Sulfamethoxazole + trimethoprim (cotrimoxazole) Sulfadoxine + pyrimethamine (fansidar) Use alternative drug Estrogens, including estrogen-containing contraceptives, thiazide diuretics, (may inhibit lactation) ergometrine Safe in usual dosage Most commonly used drugs: Monitor baby Analgesics and antipyretics: short courses of paracetamol, acetylsalicylic acid, ibuprofen; occasional doses of morphine and pethidine Antibiotics: ampicillin, amoxicillin, cloxacillin and other penicillins Erythromycin Antituberculosis drugs, antileprosy drugs (see dapsone above) 2 Antimalarials (except mefloquine, fansidar) Antihelminthics, antifungals Bronchodilators (e.g. salbutamol), corticosteroids, antihistamines, antacids, drugs for diabetes, most antihypertensives, digoxin Nutritional supplements of iodine, iron vitamins

sult in a higher mortality than the mortality no other fluids are given, there is a risk that the caused by transmission of HIV through breast infant develops hypernatremic dehydration, milk. It is therefore recommended by the UN which in severe cases can cause convulsions, agencies that breastfeeding should only be avoid- brain damage and death. This can be prevented ed if replacement feeding is acceptable, feasible, by supervision and support during the initiation affordable, sustainable and safe [7] . If that is not of breastfeeding, monitoring weight loss and the case, it is recommended that the mother urine production, and provision of other fluids if breastfeeds exclusively for the first 6 months, as there are signs of dehydration. this practice has been found to be associated with a three- to fourfold decreased risk of transmis- Environmental Contaminants sion compared to non-exclusive breastfeeding. The content of environmental contaminants is After 6 months breastfeeding should stop as soon higher in breast milk than in cow’s milk or infant as it is possible to provide an adequate and safe formula, because of the accumulation particular- diet without breast milk. ly of lipid-soluble contaminants in maternal tissues. Several studies have shown an association Hypernatremic Dehydration between high levels of contaminants in the moth- If there are problems during the first 1–2 weeks er’s blood and negative effects on health and de- after delivery in initiating milk production and velopment of the infant. However, it is difficult to

Breastfeeding 87 disentangle the intrauterine exposure from the Table 3. The Baby-Friendly Hospital Initiative: ten steps exposure through breast milk. There is general to successful breastfeeding agreement that the positive effects of breastfeed- – Have a written breastfeeding policy that is routinely ing outweigh the potential negative effects, but communicated to all healthcare staff also that it is important to reduce the level of con- – Train all healthcare staff in skills necessary to imple- taminants in the environment and the mother’s ment this policy – Inform all pregnant women about the benefits and diet. management of breastfeeding – Help mothers initiate breastfeeding within 1.5 h of Maternal Medication birth Most drugs given to a breastfeeding mother are – Show mothers how to breastfeed and maintain lactation, even if they should be separated from their excreted in her milk. If possible, maternal medi- infants cation should therefore be avoided. However, – Give newborn infants no food or drink other than only a few drugs are contraindicated, i.e. antican- breast milk, unless medically indicated cer drugs and radioactive substances. Other – Practice rooming in – that is, allow mothers and infants to remain together 24 h/day drugs might be given while monitoring the infant – Encourage breastfeeding on demand or alternative drugs may be considered. For an – Give no artificial teats or pacifiers (also called dum- overview see table 2 [8] . mies or soothers) to breastfeeding infants – Foster the establishment of breastfeeding support groups and refer mothers to them on discharge from the hospital or clinic Support of Breastfeeding

Many factors influence the initiation and duration of breastfeeding: cultural attitudes, the mother’s perception, and the attitudes of friends Breastfeeding of the Hospitalized Infant and family. The health profession plays an important role in educating and supporting the Breastfeeding is especially important in preterm mother in breastfeeding. Traditional hospital infants, because human milk appears to have a routines with separation of the mother and in- protective effect on the immature gut. Preterm fant, scheduled feeding intervals, and provisions infants have a higher protein need, which should of other drinks have a negative impact on the be covered by adding an appropriate human milk prevalence of breastfeeding. This is the reason fortifier. If the mother cannot supply milk for her why UNICEF and WHO launched the Baby infant, provision of donor milk should be consid- Friendly Hospital Initiative 1992. By training ered. This could be provided from individual do- hospital staff in the ten steps to successful breast- nors or from a human milk bank. If donor milk feeding (table 3) it has been possible to increase is used, there are a number of procedures on test- breastfeeding rates in many settings. Health pro- ing, storage and pasteurization that have to be fessionals should also be trained to solve com- followed [9] . Human milk also has advantages for mon problems during the first days after delivery, many term infants with medical problems. Moth- such as positioning of the infant, sore nipples, ers should be supported to express milk for their and sucking difficulties. To stop the negative in- infants if they can suck. This milk can be fed by fluences from the marketing of infant formula, tube, bottle or cup. the World Health Assembly has adopted an international code on the marketing of breast milk substitutes.

88 Pediatric Nutrition in Practice Conclusions • HIV-positive mothers should refrain from breastfeeding if replacement feeding is accept- • Populations of breastfed infants have less in- able, feasible, affordable, sustainable and safe fections and most likely less immune-related • Feeding of human milk to preterm infants diseases, such as asthma, diabetes, and in- protects the immature gut and decreases the flammatory bowel diseases, a small advantage risk of necrotizing enterocolitis in cognitive development and some protec- • If the mother cannot provide breast milk for tion against non-communicable diseases, e.g. her preterm infant, provision of donor milk obesity should be considered • For the mother breastfeeding results in lactational amenorrhea and child spacing, which is important in populations with low use of contraceptives

References

1 ISRHML Bibliographies of Scientific 5 Effect of breastfeeding on infant and 7 WHO: HIV and Infant Feeding Techni- Papers on Human Milk and Lactation. child mortality due to infectious dis- cal Consultation, Geneva, WHO, 2006. 2 www.isrhml.org under ‘Publications’. eases in less developed countries: a www.who.int/child-adolescent-health/ 2 Schack-Nielsen L, Michaelsen KF: pooled analysis. WHO Collaborative New_Publications/NUTRITION/con- Breast feeding and future health. Curr Study Team on the Role of Breastfeed- sensus_statement.pdf.

Opin Clin Nutr Metab Care 2006; 9: ing on the Prevention of Infant Mortal- 8 WHO: Breastfeeding and Maternal

289–296. ity. Lancet 2000; 355; 451–455. Medication. Recommendations for 3 Breastfeeding and Maternal and Infant 6 Dewey KG, Peerson JM, Brown KH, et Drugs in the 11th WHO Model List of Health Outcomes in Developed Coun- al: Growth of breastfed infants deviates Essential Drugs. www.who.int/child- tries. Rockville, Agency for Healthcare from current reference data: a pooled adolescent-health/New_Publications/ Research and Quality, 2007. Available analysis of US, Canadian, and Europe- NUTRITION/BF_Maternal_Medica- as pdf at www.ahrq.gov/clinic/tp/ an data sets. World Health Organiza- tion.pdf. brfouttp.htm. tion Working Group on Infant Growth. 9 Lawrence RA, Lawrence RM: Breast-

4 Horta BL, Bahl RB, Martines JC, Vic- Pediatrics 1995; 96: 495–503. feeding: A Guide for the Medical Pro- tora CG: Evidence of the Long-Term fession, ed 6. St Louis, Mosby, 2005. Effects of Breastfeeding: Systematic 10 Koletzko B (ed): Kinder- und Jugend- Reviews and Metaanalysis. Geneva medizin, ed 13. Berlin, Springer, 2007. WHO, 2007. Available as pdf at www. who.int/child-adolescent-health.

Breastfeeding 89 Koletzko B. (ed): Pediatric Nutrition in Practice. Basel, Karger, 2008, pp 90–97

2 Nutrition of Healthy Infants, Children and Adolescents

2.2 Formula Feeding Dominique Turck

Key Words an infant formula intended to serve as a breast -Infant formula ؒ Follow-on formula ؒ Soy formula ؒ milk substitute, specially manufactured to satis -Food Safety ؒ Codex Alimentarius ؒ Enterobacter fy, by itself, the particular nutritional require sakazakii ؒ Prebiotics ؒ Probiotics ؒ Long-chain ments of infants during the first months of life up -polyunsaturated fatty acids ؒ Antiregurgitation to the introduction of appropriate complemen formula tary feeding, and thereby to promote normal growth and development. Key Messages Infant formula is a product based on the milk R The standard of the Codex Alimentarius defining of cows or other animals and/or other edible con- the composition of infant formula intended to stituents of animals, including fish, or of plant meet the nutritional needs of healthy infants from origin, which have been proved to be suitable for birth to 1 year of age was updated in July 2007 infant feeding. R Infant formula should only contain components in Gross compositional similarity with the hu- certain amounts that serve a nutritional purpose or man milk of healthy women is not an adequate other benefit R Powdered formula is not a sterile product and may indicator of the safety and suitability of infant contain pathogenic bacteria such as Enterobacter formula [3] . The adequacy of infant formula com- sakazakii that can cause devastating infections position should be determined by a comparison R No general recommendation on the addition of of its effects on physiological (e.g. growth pat- prebiotics, probiotics, and thickening agents to in- terns), biochemical (e.g. plasma markers) and fant formula for healthy, thriving term infants can be made functional (e.g. immune responses) outcomes in R Soy protein infant formula has no nutritional ad- infants fed formulae with those of healthy, exclu- vantages over cow’s milk protein infant formula sively breastfed infants. Copyright © 2008 S. Karger AG, Basel Infant formulae should only contain components in certain amounts that serve a nutritional purpose or other benefit. Since dietary composi- Introduction tion in infants has a major impact on short- and long-term child health and development, the sci- Breastfeeding is the ideal form of infant feeding entific evidence to support modifications of in- which should be actively supported, promoted fant formulae beyond the established standards and protected [1, 2] . Infants who cannot be breast- should be evaluated by independent scientific fed (or should not receive breast milk, or for bodies prior to the acceptance of introduction of whom breast milk is not available) should receive such products to the market. Recommendations for Infant Formula to that of ‘infant formulae’ defined as foodstuffs Composition intended for use by infants during the first months of life and satisfying by themselves the The Codex Alimentarius (Latin for ‘food code’) nutritional requirements of such infants until the is a collection of internationally recognized stan- introduction of appropriate complementary feed- dards, guidelines, codes of practice and other ing (table 2 ). recommendations related to foods, food production and food safety [4] . These texts are developed by the Codex Alimentarius Commission Preparation, Storage and Handling of Infant that was established in 1963 by the Food and Ag- Formula riculture Organization of the United Nations (FAO), and the World Health Organization Powdered formula is not a sterile product and (WHO). The aims of the Commission are to pro- may contain pathogenic bacteria such as Entero- tect the health of consumers, to ensure fair prac- bacter sakazakii that can cause devastating sep- tices in the international food trade and to pro- sis, particularly in the first 2 months of life. In the mote coordination of all food standards work un- home setting, powdered formula should be fresh- dertaken by international governmental and ly prepared for each feed. Written guidelines for non-governmental organizations. The Codex the preparation and handling of formula should Standard 72 defining the compositional, quality be established for hospitals and daycare centers, 2 and safety requirements for infant formula in- and their implementation should be monitored tended to meet the nutritional needs of healthy [9] . If formula needs to be prepared in advance, it infants from birth to 1 year of age was adopted by should be prepared on a daily basis and should be the Codex Alimentarius Commission in 1981 [5] . kept at 4 ° C or below for not more than 30 h. The The Codex Standard 72 was updated in 2007 [6] . use of sterile liquid formula is encouraged for Infant formula prepared ready for consumption healthy newborn infants in maternity wards. must contain per 100 kcal the nutrients listed in table 1, with minimum and maximum levels where applicable. Addition of Ingredients to Infant Formula

Thickening Agents The Concept of Follow-On Formula It is clear from clinical experience that the addition of thickening agents as starch or carob bean The European Union Commission Directive gum to infant formula (antireflux or antiregurgi- 91/321/EEC of 14 May 1991 [7] defined follow-on tation formula) can reduce moderate regurgita- formulae designed for infants after the introduction and decrease nutrient losses in case of failure tion of foods other than milk. ‘Follow-on formu- to thrive. However, since very few nutritional lae’ are foodstuffs intended for particular nutri- studies have been performed in infants, antire- tional use by infants when appropriate comple- gurgitation formulae should not be used indis- mentary feeding is introduced and constituting criminately in healthy, thriving infants who spit the principal liquid element in a progressively di- up [10] . versified diet. They should not be used as breast milk substitutes during the first 6 months of life. Long-Chain Polyunsaturated Fatty Acids In the updated Directive 2006/141/EC of 22 De- While there are indications that a supply of doco- cember 2006 [8] , their composition is very close sahexaenoic acid and arachidonic acid in infancy

Formula Feeding 91 Table 1. Essential composition of infant formula in liquid or powdered form [6]

Component Unit Minimum Maximum GUL1

Energy kcal/100 ml 60 70 – Proteins2 1.8 3.0 – Lipids3 Total fat g/100 kcal 4.4 6.0 – Linoleic acid mg/100 kcal 300 – 1,400 ␣-Linolenic acid mg/100 kcal 50 – – Ratio linoleic/␣-linolenic acid 5:1 15:1 – Lauric + myristic acids % total fatty acids – 20 – Trans fatty acids % total fatty acids – 3 – Erucic acid % total fatty acids – 1 – Total phospholipids mg/100 kcal – 300 – Carbohydrates4 Total carbohydrates g/100 kcal 9.0 14.0 – Vitamins Vitamin A5 ␮g RE/100 kcal 60 180 – Vitamin D6 ␮g/100 kcal 1 2.5 – Vitamin E7 mg ␣-TE/100 kcal 0.5 – 5 Vitamin K ␮g/100 kcal 4–27 Thiamin ␮g/100 kcal 60 – 300 Riboflavin ␮g/100 kcal 80 – 500 Niacin8 ␮g/100 kcal 300 – 1,500 Vitamin B6 ␮g/100 kcal 35 – 175 Vitamin B12 ␮g/100 kcal 0.1 – 1.5 Pantothenic acid ␮g/100 kcal 400 – 2,000 Folic acid ␮g/100 kcal 10 – 50 Vitamin C9 mg/100 kcal 10 – 70 Biotin ␮g/100 kcal 1.5 – 10 Minerals and trace elements Iron mg/100 kcal 0.45 – –10 Calcium mg/100 kcal 50 – 140 Phosphorus mg/100 kcal 25 – 10011 Ratio calcium/phosphorus mg/mg 1:1 2:1 – Magnesium mg/100 kcal 5 – 15 Sodium mg/100 kcal 20 60 – Chloride mg/100 kcal 50 160 – Potassium mg/100 kcal 60 180 – Manganese ␮g/100 kcal 1 – 100 Iodine ␮g/100 kcal 10 – 60 Selenium ␮g/100 kcal 1– 9 Copper12 ␮g/100 kcal 35 – 120 Zinc mg/100 kcal 0.5 – 1.5 Fluoride13 ␮g/100 kcal – 100 – Other substances Choline mg/100 kcal 7 – 50 Myoinositol mg/100 kcal 4 – 40 L-Carnitine mg/100 kcal 1.2 – – Optional ingredients14, 15 Taurine mg/100 kcal – 12 – Total nucleotides16 mg/100 kcal – – Docosahexaenoic acid17 % total fatty acids – – 0.5

92 Pediatric Nutrition in Practice 1 Guidance upper levels (GULs) are for nutrients without 8 Niacin refers to preformed niacin. sufficient information for a science-based risk assess- 9 Expressed as ascorbic acid. This GUL has been set to ment. These values are values derived on the basis of account for possible high losses over shelf-life in liquid meeting nutritional requirements of infants and an es- formulae; for powdered products lower upper levels tablished history of apparent safe use. Nutrient con- should be aimed for. tents in infant formulae should usually not exceed the 10 Levels may need to be determined by national au- GULs unless higher nutrient levels cannot be avoided thorities. due to high or variable contents in constituents of in- 11 This GUL should accommodate higher needs with soy fant formulae or due to technological reasons. formula. 2 The minimum value applies to cow’s milk protein. For 12 Adjustment may be needed in these levels for infant infant formula based on non-cow’s milk protein other formula made in regions with a high copper content in minimum values may need to be applied. For infant for- the water supply. mula based on soy protein isolate, a minimum value of 13 Fluoride should not be added to infant formula. In 2.25 g/100 kcal applies. Infant formula based on non- any case its level should not exceed 100 ␮g/100 kcal. hydrolyzed milk protein containing less than 2 g pro- 14 The following substances may be added in conform- tein/100 kcal and infant formula based on hydrolyzed ity with national legislation. 15 2 protein containing less than 2.25 g protein/100 kcal Only L(+)-lactic acid producing cultures may be should be clinically evaluated. used. 3 Commercially hydrogenated oils and fats must not be 16 Levels may need to be determined by national au- used in infant formula. thorities. 4 Lactose and glucose polymers should be the preferred 17 If docosahexaenoic acid (22:6n-3) is added to infant carbohydrates in formula based on cow’s milk protein formula, the arachidonic acid (20:4n-6) content should and hydrolysed protein. Only precooked and/or gelati- reach at least the same concentration as docosahexa- nized starches, gluten-free by nature, may be added to enoic acid. The content of eicosapentaenoic acid (20:5n- infant formula up to 30% of total carbohydrates and up 3), which can occur in sources of long-chain PUFA, to 2 g/100 ml. Sucrose, unless needed, and the addition should not exceed the content of docosahexaenoic of fructose as an ingredient should be avoided in infant acid. National authorities may deviate from the above formula, because of life-threatening symptoms in conditions, as appropriate for the nutritional needs. young infants with unrecognized hereditary fructose intolerance. 5 Expressed as retinol equivalents (RE). 1 ␮g RE = 3.33 IU. Vitamin A = 1 ␮g all-trans retinol. Retinol contents must be provided by preformed retinol, while any carotenoid content should not be included in the calculation and declaration of vitamin A activity. 6 Calciferol: 1 ␮g calciferol = 40 IU vitamin D. 7 1 mg ␣-TE (␣-tocopherol equivalent) = 1 mg D-␣-tocopherol. Vitamin E content must be at least 0.5 mg ␣-TE/g polyunsaturated fatty acid (PUFA), using the following factors of equivalence to adapt the minimal vitamin E content to the number of fatty acid double bonds in the formula: 0.5 mg ␣-TE/g linoleic acid (18:2n- 6); 0.75 mg ␣-TE/g ␣-linolenic acid (18:3n-3); 1.0 mg ␣-TE/g arachidonic acid (20:4n-6); 1.25 mg ␣-TE/g eicosapentaenoic acid (20:5n-3); 1.5 mg ␣-TE/g docosahexaenoic acid (22:6n-3).

Formula Feeding 93 Table 2. Essential composition of follow-on formulae (FOF) when reconstituted as instructed by the manufacturer [8]

Component Unit Minimum Maximum

Energy kcal/100 ml 60 70 Proteins FOF manufactured from cow’s milk proteins g/100 kcal 1.8 3.5 FOF manufactured from protein hydrolysates or from soy protein isolates, alone or in a mixture with cow’s milk proteins g/100 kcal 2.25 3.5 Lipids1 Total fat g/100 kcal 4.0 6.0 Linoleic acid mg/100 kcal 300 1,200 ␣-Linolenic acid mg/100 kcal 50 – Ratio linoleic/␣-linolenic acid 515 Lauric and/or myristic acid % fat – 20 Trans fatty acids % fat – 3 Erucic acid % fat – 1 Phospholipids g/l – 2 Long-chain (20 and 22 carbon atoms) polyunsaturated fatty acids (LCP)2 % fat n-3 LCP 1 n-6 LCP 2 Arachidonic acid –1 Carbohydrates Total carbohydrates g/100 kcal 9.0 14.0 Lactose3 g/100 kcal 4.5 – Sucrose and/or fructose and/or honey4 % carbohydrates – 20 Glucose5 g/100 kcal – 2 Fructo-oligosaccharides and galacto-oligosaccharides6 g/l – 8 Vitamins Vitamin A7 ␮g – RE/100 kcal4 60 180 Vitamin D8 ␮g/100 kcal 13 Vitamin E9 mg ␣-TE/100 kcal 0.510 5 Vitamin K ␮g/100 kcal 425 Thiamin ␮g/100 kcal 60 300 Riboflavin ␮g/100 kcal 80 400 Niacin11 ␮g/100 kcal 300 1,500 Vitamin B6 ␮g/100 kcal 35 175 Vitamin B12 ␮g/100 kcal 0.1 0.5 Pantothenic acid ␮g/100 kcal 400 2,000 Folic acid ␮g/100 kcal 10 50 Vitamin C mg/100 kcal 10 30 Biotin ␮g/100 kcal 1.5 7.5 Minerals and trace elements FOF manufactured from cow’s milk proteins or protein hydrolysates Iron mg/100 kcal 0.6 2 Calcium mg/100 kcal 50 140 Phosphorus mg/100 kcal 25 90 Ratio calcium/phosphorus mg/mg 1 2 Magnesium mg/100 kcal 5 15 Sodium mg/100 kcal 20 60 Chloride mg/100 kcal 50 160

94 Pediatric Nutrition in Practice Table 2 (continued)

Component Unit Minimum Maximum

Potassium mg/100 kcal 60 160 Manganese ␮g/100 kcal 1 100 Iodine ␮g/100 kcal 10 50 Selenium ␮g/100 kcal 19 Copper ␮g/100 kcal 35 100 Zinc mg/100 kcal 0.5 1.5 Fluoride ␮g/100 kcal – 100 FOF manufactured from soy protein isolates, alone or in a mixture with cow’s milk proteins12 Iron mg/100 kcal 0.9 2.5 Phosphorus mg/100 kcal 30 100 Optional ingredients Taurine mg/100 kcal – 12 Total nucleotides mg/100 kcal – 5 Cytidine 5؅-monophosphate – 2.5 Uridine 5؅-monophosphate – 1.75 Adenosine 5؅-monophosphate – 1.5 Guanosine 5؅-monophosphate – 0.5 Inosine 5؅-monophosphate – 1.0 2 1 The use of sesame seed oil and cotton seed oil must be 7 RE = All trans retinol equivalent. prohibited. 8 In the form of cholecalciferol, of which 10 ␮g = 400 IU 2 The eicosapentaenoic acid (20:5n-3) content must not of vitamin D. exceed the docosahexaenoic acid (22:6n-3) content. 9 ␣-TE = D-␣-Tocopherol equivalent. The docosahexaenoic acid content must not exceed 10 0.5 mg ␣-TE/g polyunsaturated fatty acids expressed that of n-6 LCP. as linoleic acid as corrected for the double bonds but 3 This provision does not apply to follow-on formulae in in no case less than 0.5 mg/100 available kcal: 0.5 mg which soy protein isolates represent more than 50% of ␣-TE/1 g linoleic acid (18:2n-6); 0.75 mg ␣-TE/1 g ␣-lino- the total protein content. lenic acid (18:3n-3); 1.0 mg ␣-TE/1 g arachidonic acid 4 Honey must be treated to destroy spores of Clostridi- (20:4n-6); 1.25 mg ␣-TE/1 g eicosapentaenoic acid um botulinum. (20: 5n-3); 1.5 mg ␣-TE/1 g docosahexaenoic acid (22: 5 Glucose may only be added to follow-on formulae 6n-3). manufactured from protein hydrolysates. 11 Preformed niacin. 6 Fructo-oligosaccharides (FOS) and galacto-oligosac- 12 All requirements defined for FOF manufactured from charides (GOS) may be added to follow-on formulae in cow’s milk proteins or protein hydrolysates must ap- a combination of 90% GOS and 10% FOS. ply.

may have some beneficial effects, there is no Ingredients Modulating the Intestinal Microflora unanimous agreement that an exogenous supply (see Chapter 1.7) is needed, at least not after the first few months of Prebiotics (mainly fructo-oligosaccharides and life [11] . However, there is no evidence to suggest galacto-oligosaccharides) are undigestible food that concentrations within the range found in components stimulating the growth and/or ac- human milk are harmful. The addition of doco- tivity of one or a limited number of bacteria in the sahexaenoic acid and arachidonic acids is there- colon and thereby improving host health [12] , fore allowed in infant formula ( table 1 ). whereas probiotics (mainly Bifidobacterium bifi-

Formula Feeding 95 dum and Lactobacillus rhamnosus GG ) are live during the first 6 months of life. They have no microbial food ingredients that are beneficial to indication in the prevention or management of health [12] . Although they may have health ben- infantile colic, regurgitation or prolonged cry- efits, no general recommendation on the supple- ing. mentation of prebiotics, probiotics, and synbiot- ics, i.e. a mixture of prebiotics and probiotics, can be made in infancy [12–14] . Conclusions

Infant formulae: Indications for Soy Protein Formula • are breast milk substitutes satisfying the nutritional requirements of infants from birth to Soy is a source of protein that is inferior to cow’s 1 year of age. Their composition should follow milk protein, with a lower digestibility and bio- the Codex Alimentarius Standard revised in availability. For soy protein infant formulae, only 2007 [6] soy protein isolates can be used. Soy protein for- • are products based on milk of cows or other mulae should only be used in specified circum- animals and/or other edible constituents of stances because they may have nutritional disad- animals, including fish, or of plant origin vantages and contain high concentrations of • are not sterile products when powdered. phytate, aluminum and phytoestrogens (isofla- Guidelines for their preparation and handling vones), the long-term effects of which are un- are necessary in institutional settings known [15] . Soy protein formulae should not be No general recommendations on the addition used in preterm infants. Indications include se- of prebiotics, probiotics, and thickening agents to vere persistent lactose intolerance, galactosemia, infant formula for healthy, thriving term infants and vegan concepts. Soy protein formulae play no can be made. Soy protein formulae are not the role in the prevention of allergic diseases and first choice of feeding for healthy infants. should not be used in infants with food allergy

References

1 World Health Organization: Fifty- 4 Codex Alimentarius: Understanding 6 Codex Alimentarius: Joint FAO/WHO Fourth World Health Assembly. Reso- the Codex Alimentarius, ed 3. World Food Standards Programme. Codex lution WHA 54.2. Agenda Item 13.1 Health Organization, Food and Agri- Alimentarius Commission. 13th Ses- Infant and young child nutrition. culture Organization of the United sion, FAO Headquarters, Rome, July 18 May 2001. Nations. ftp://ftp.fao.org/codex/ 2007. http://www.codexalimentarius. 2 Schack-Nielsen L, Michaelsen KF: Publications/understanding/Under- net/download/report/684/ Breast feeding and future health. Curr standing_EN.pdf. al30REPe[1].pdf.

Opin Clin Nutr Metab Care 2006; 9: 5 Codex Alimentarius: Codex Standard 7 Commission Directive 91/321/EEC of 289–296. for Infant Formula. Codex Stan 72– 14 May 1991 on Infant Formulae and 3 Koletzko B, Baker S, Cleghorn G, et al: 1981. 1981 www.codexalimentarius. Follow-On Formulae. Official Journal Global standard for the composition of net/download/standards/288/CXS_ of the European Communities, infant formula: recommendations of an 072e.pdf. 04.07.1991, L 175, p 35. ESPGHAN coordinated international 8 Commission Directive 2006/141/EC of expert group. J Pediatr Gastroenterol 22 December 2006 on Infant Formulae

Nutr 2005; 41: 584–599. and Follow-on Formulae. Official Jour- nal of the European Communities, 30.12.2006, L 401, p 33.

96 Pediatric Nutrition in Practice 9 Agostoni C, Axelsson I, Goulet O, et al; 11 Jensen CL, Heird WC: Lipids with an 14 Agostoni C, Goulet O, Kolacek S, et al; ESPGHAN Committee on Nutrition: emphasis on long-chain polyunsatu- ESPGHAN Committee on Nutrition:

Preparation and handling of powdered rated fatty acids. Clin Perinatol 2002; Fermented infant formulae without live

infant formula: a commentary by the 29: 261–281. bacteria. J Pediatr Gastroenterol Nutr

ESPGHAN Committee on Nutrition. J 12 Agostoni C, Axelsson I, Braegger C, et 2007; 44: 392–397.

Pediatr Gastroenterol Nutr 2004; 39: al; ESPGHAN Committee on Nutrition: 15 Agostoni C, Axelsson I, Goulet O, et al; 320–322. Probiotic bacteria in dietetic products ESPGHAN Committee on Nutrition: 10 Aggett PJ, Agostoni C, Goulet O, et al; for infants: a commentary by the Soy protein infant formulae and follow- ESPGHAN Committee on Nutrition: ESPGHAN Committee on Nutrition. J on formulae: a commentary by the

Antireflux or antiregurgitation milk Pediatr Gastroenterol Nutr 2004; 38: ESPGHAN Committee on Nutrition. J

products for infants and young chil- 365–374. Pediatr Gastroenterol Nutr 2006; 42: dren: a commentary by the ESPGHAN 13 Agostoni C, Axelsson I, Goulet O, et al; 352–361. Committee on Nutrition. J Pediatr Gas- ESPGHAN Committee on Nutrition:

troenterol Nutr 2002; 34: 496–498. Prebiotic oligosaccharides in dietetic products for infants: a commentary by the ESPGHAN Committee on Nutri-

tion. J Pediatr Gastroenterol Nutr 2004;

39: 465–473.

Formula Feeding 97 Koletzko B. (ed): Pediatric Nutrition in Practice. Basel, Karger, 2008, pp 98–101

2 Nutrition of Healthy Infants, Children and Adolescents

2.3 Marketing of Breast-Milk Substitutes Vinodini Reddy

Key Words in accordance with codex standards, provide an Marketing, breast-milk substitutes ؒ Breast-milk alternate source of nutrition. Bottle-fed infants -substitutes ؒ Infant formula, marketing living in poor environments in developing coun tries are at a high risk of malnutrition and even death. It is estimated that 1.5 million babies die Key Messages each year because they are not adequately breast- R Breast milk is the best source of nutrition for healthy fed [1] . When a mother uses an alternative to breast infants. For those who cannot breastfeed, infant milk to feed her baby, it is important that she formula provides an alternate source of nutrition makes an informed decision. Although it is over R Mothers must be informed about the benefits of 25 years since the introduction of the internation- breastfeeding and the risks associated with bottle- feeding al code for the marketing of breast-milk substi- R The international code for the marketing of breast- tutes [2] , which aims to encourage breastfeeding milk substitutes was introduced to promote breast- and to restrict the promotion of infant formula, it feeding and to ensure that the marketing of breast- is still not universally applied. There is a need for milk substitutes is appropriate more effective implementation of the code. R The reported violations of the code call for enforcement of stricter rules R Health professionals and nongovernmental organizations concerned with child care should moni- The International Code tor the use of formula milk and report violations to the appropriate body The International Code of Marketing of Breast- Copyright © 2008 S. Karger AG, Basel Milk Substitutes was adopted by the World Health Assembly (WHA) in 1981 to promote breastfeeding and to ensure that marketing of breast-milk Introduction substitutes and feeding bottles is appropriate [2] . The member States of WHA are to implement the The first 2 years of life are critical for the promo- code in national measures as a minimum re- tion of healthy growth and development of chil- quirement to promote healthy practices with re- dren. It is of utmost importance that the foods spect to infant and young child feeding. Manu- children receive are nutritionally adequate and facturers and distributors are called on to abide safe. Exclusive breastfeeding for the first 6 months by the international code independent of other is recommended by the WHO for all populations. measures. Non-governmental organizations, pro- For those who cannot breastfeed, infant formula fessional groups, institutions and individuals are and other breast-milk substitutes, manufactured called on to report violations. Extracts from the International Code ples of infant formula, other breast milk substitutes and feeding bottles, in contravention of ar- Article 2 (products covered by the code): The code ticles 5.2 and 7.4 of the international code [3] . applies to the marketing, and practices related Most of the samples were reported to have come thereto, of the following products: breast-milk from a health facility; this suggests that samples substitutes, including infant formula; other milk given to facilities were passed on to mothers, products; foods and beverages, including bottle- whether or not that was the intention of the com- fed complementary foods, when marketed or pany donating the samples. otherwise represented to be suitable for use as a Breastfeeding campaigners have persistently partial or total replacement of breast milk, feed- highlighted breaches by companies in adhering ing bottles, and teats. to the WHO code. A recent briefing by Save the Article 5.2 (provision of samples): Manufac- Children and an investigation by the Guardian turers and distributors should not provide, di- include a catalog of evidence. For example, the rectly or indirectly, pregnant women, mothers, or briefing includes a report from Botswana where members of their families with samples of prod- 30% of mothers reported to have been advised by ucts within the scope of this code. a healthcare professional to use a specific brand Article 7.2 (provision of information for health of infant formula [4] . The Guardian investigation workers): Information provided by manufactur- in Dhaka found that the walls of a doctor’s wait- ers and distributors to health professionals re- ing room were covered with posters showing 2 garding products in the scope of this code should healthy babies and the brands of infant formula be restricted to scientific and factual matters, and [5] . Practices recently reported from the Philip- such information should not imply or create a be- pines include targeting mothers with ‘mothering lief that bottle feeding is equivalent or superior to classes’ and offering financial incentives for breastfeeding. healthcare staff [6] . Community health workers Article 7.3 (provision of inducements to health received gifts such as T-shirts or jackets, and workers): No financial or material inducements mothers were given free samples of infant formu- to promote products within the scope of this code la. Studies show that distribution of free samples should be offered by manufacturers or distribu- has a detrimental effect on breastfeeding [7, 8]. tors to health workers or members of their families. Article 7.4 (provision of samples to health Monitoring the Code workers): Samples of infant formula or other products within the scope of this code should not Information provided by monitoring helps inter- be provided for health workers except when nec- national organizations like the WHO and UNI- essary for the purpose of professional evaluation CEF, and national governments in the implemen- or research at the institutional level. tation of the code and to stop specific violations in a country. The reports on violations demonstrate the need for transparent, independent and Violations of the International Code effective controls on the marketing of baby food and bottles. Governments should ensure a con- Violations of the code are common throughout sistent strategy of monitoring involving investi- the world. For example, a survey carried out in 4 gation, observation and recording of informa- countries, Bangladesh, Poland, South Africa and tion. The basics of monitoring include familiar- Thailand, revealed the distribution of free sam- ization with the main points of the international

Marketing of Breast-Milk Substitutes 99 code and the national measures; obtaining infor- mother and child, bestows upon the newborn in- mation on the breast-milk substitutes locally fant protection against infection, and contributes used; recording details about the company and to protecting the mothers from closely spaced brand names, hospitals/clinics where infant for- pregnancy. Mothers should be informed about mula is used; descriptions of posters, displays, the benefits of breastfeeding and the disadvan- etc., and the reporting of violations to the appro- tages associated with bottle feeding. Hospitals priate body. and maternity units can set important examples for new mothers. Despite the UNICEF’s Baby- Friendly Hospital Initiative launched in 1991 to Campaign for Ethical Marketing support breastfeeding [10] , mothers still receive contradictory advice. Those delivered normally It is now recognized that voluntary initiatives can initiate breastfeeding within half an hour of alone are inadequate for implementation of the birth, but they are often advised to give water or code for the marketing of breast-milk substitutes. a breast-milk substitute which might have a neg- Health professionals and breastfeeding organiza- ative impact [11] . The training of healthcare staff tions call for enforcement of stricter rules. must be strengthened. Governments, organiza- Under the international code, information tions of pediatricians, obstetricians and other provided by the manufacturers should not imply healthcare professionals, as well as other non- or create a belief that bottle feeding is equivalent governmental organizations play important roles or superior to breastfeeding. But many leading in implementing adequate standards and prac- brands of infant formula carry misleading nutri- tices for the promotion, protection and support tion claims. Recently, legislation of the European of breastfeeding, and for the restriction of undue Community has provided a limited list of accept- marketing activities for breast-milk substitutes. able claims, as well as a process by which any additional claims must be fully evaluated before they can be used [9], and these regulations are to Conclusions be implemented in the national legislation of all member states. Baby milk manufacturers are or- • Breast milk is the best source of nutrition for dered to drop all nutrition claims of baby foods, infants. For those who cannot breastfeed, in- which suggest that they would be a superior alter- fant formula provides an alternate source of native to breast milk. The aim is to ensure that nutrition mothers are not unduly influenced when decid- • When a mother uses an alternative to breast ing on their feeding practices. milk to feed her baby, it is important that she makes an informed decision and is not pres- sured by commercial promotions to use a sub- E d u c a t i o n C a m p a i g n stitute • The International Code of Marketing of Health professionals and breastfeeding advocates Breast-Milk Substitutes was introduced to consider that the lack of awareness about the im- promote breastfeeding and to regulate the portance of breastfeeding is an important con- marketing of breast-milk substitutes, and it tributory factor for the introduction of bottle needs to be strictly applied and enforced feeding. Breastfeeding is the best source of nutrition for healthy babies, it promotes the development of the emotional bonding between the

100 Pediatric Nutrition in Practice References

1 World Health Organization: Infant and 5 Moorhead J: Milking It. Guardian, 15 9 Commission Directive 2006/141/EC of Young Child Nutrition. Geneva, WHO, May 2007. 22 December 2006 on Infant Formulae 1993, EB93/17. 6 Help the Philippines Stand Up to Com- and Follow-On Formulae and Amend- 2 World Health Organization: Interna- pany Bullying: www.babymilkaction. ing Directive 1999/21/EC. Official Jour- tional Code of Marketing of Breast- org/CEM/cemnov06.html#1. nal of the European Communities, Milk Substitutes. Geneva, WHO, 1981. 7 Frank DA, Wirtz JS, Sorenson JR, 30.12.2006, L 401, pp 1–33. 3 Taylor A: Violations of the internation- Heeren T: Commercial discharge packs 10 The Baby-Friendly Hospital Initiative: al code of marketing of breast milk and breastfeeding counselling: effects http://www.unicef.org/nutrition/ substitutes: prevalence in four coun- on infant feeding practices in a ran- index_24806.html.

tries. BMJ 1998; 316: 1117–1122. domized trial. Pediatrics 1987; 80: 845– 11 Szajewska H, Horvath A, Koletzko B, 4 Save the Children: A Generation on 854. Kalisz M: Effects of brief exposure to Baby Milk Marketing Still Putting 8 Pérez-Escamilla R, Pollitt E, Lönnerdal water, breast-milk substitutes, or other Children’s Lives at Risk. www. B, Dewey K: Infant feeding policies in liquids on the success and duration of savethechildren.org 22 May 07. maternity wards and their effect on breastfeeding: a systematic review.

breast-feeding success: an analytical Acta Paediatr 2006; 95: 145–152.

overview. Am J Public Health 1994; 84: 89–97. 2

Marketing of Breast-Milk Substitutes 101 Koletzko B. (ed): Pediatric Nutrition in Practice. Basel, Karger, 2008, pp 102–105

2 Nutrition of Healthy Infants, Children and Adolescents

2.4 Complementary Foods Mary Fewtrell

Key Words and liquids other than breast milk or infant for- .Complementary feeding ؒ Infant ؒ Breastfeeding mulas Complementary foods are required during the second part of the first year of life for both Key Messages nutritional and developmental reasons, and to R Complementary foods are defined by the WHO as enable the transition from milk feeding to family any food or liquid other than breast milk. However, foods. From a nutritional point of view, the abil- since many infants receive human milk substitutes ity of breast milk to meet macro- and micronutri- from the first weeks of life, other authorities have suggested that the term, complementary food, ent requirements becomes limited, while from a should be applied to foods and liquids other than developmental perspective, infants develop the breast milk or infant formulas ability to chew and start to show an interest in R Complementary foods are required for nutritional foods other than milk. and developmental reasons. They should not be Current WHO recommendations on the age introduced before 17 weeks, but all infants should start complementary foods by 26 weeks at which complementary foods should be intro- R It is important to ensure that complementary duced are based on consideration of the optimal foods provide adequate energy density (minimum duration of exclusive breastfeeding. However, 25% fat), and that the diet includes good sources of since HMS are defined by WHO as a complemen- protein, iron and zinc. Strategies used to achieve tary food, it is difficult to translate this recom- this will vary in different environments mendation to formula-fed infants. Following a Copyright © 2008 S. Karger AG, Basel systematic review [2] and expert consultation in 2001 [3] , WHO recommended that infants should be exclusively breastfed for 6 months, although Introduction this contrasts with current practice in many countries where complementary foods may be in- Complementary foods are defined by the WHO troduced starting from 3–4 months. as any food or liquid other than breast milk. This definition means that infant formulas and follow-on formulas (human milk substitutes, HMS) Timing of Complementary Feeding are regarded as complementary foods, which can be confusing, since many infants receive HMS Complementary feeding recommendations and from the first weeks of life. Other authorities practices are generally not evidence-based and (ESPGHAN [1] ) have suggested that the term, vary between countries. Gastrointestinal and re- complementary food, should be applied to foods nal functions are likely to be sufficiently mature by around 4 months of age to enable infants to support growth and development, in more afflu- process some complementary foods. With regard ent environments, achieving a better balance of to neurodevelopment, there is a range at which nutrients and avoiding excess may be more im- infants attain the necessary motor skills to cope portant. safely with complementary foods, but this is like- Nutritional recommendations for the comple- ly to fall within the 4–6 months period. There is mentary feeding period are based on the concept general consensus that complementary foods that breast milk will not meet full requirements should not be given before 17 weeks of age, as ear- for energy, protein and micronutrients beyond lier introduction may be associated with an in- about 6 months of age. Theoretically, the require- crease in fatness, respiratory symptoms and ec- ment for good quality early complementary zema later in childhood. The WHO recommends foods – particularly those rich in iron and zinc – that infants should be exclusively breastfed for 6 may be more important for breastfed infants, months before the introduction of complemen- since an infant fed entirely on HMS will have tary foods [3] . This recommendation is based on higher micronutrient intakes from milk at this the findings of a systematic review of the optimal stage. In practice, however, it is generally consid- duration of exclusive breastfeeding [2] compar- ered undesirable and impractical to have differ- ing mother and infant outcomes with exclusive ent recommendations for breastfed and formula- breastfeeding for 6 months versus 3–4 months in fed infants. 20 eligible studies. From the perspective of in- 2 fants in developed countries, one study from Be- larus found that infants who were exclusively E n e r g y breastfed for 6 months experienced less morbidity from gastrointestinal infection than those ex- Energy requirements remain high during the clusively breastfed for 3–4 months [2] . Although first year of life. The fat content of the diet is an many countries have adopted the new WHO rec- important determinant of its energy density and ommendation, sometimes with qualifications, should not be less than 25% of energy intake. A other countries still recommend 4–6 months. A higher proportion might be required if the appe- recent commentary by the ESPGHAN Commit- tite is poor, the infant has recurrent infections or tee on Nutrition considered all aspects of the tim- is fed infrequently. Reduced fat cow’s milk should ing and content of diet during the complemen- not be introduced too early as it will reduce the tary feeding period and concluded that comple- energy density of the diet. In deciding when to mentary foods should not be introduced before introduce lower fat cow’s milk, consideration 17 weeks, but that all infants should start comple- should be given to the rest of the infant’s diet, and mentary foods by 26 weeks [1] . to his or her growth. In countries with high rates of child obesity, it may be advantageous to accustom children to low fat products from a fairly ear- Content of the Diet ly age.

Most current guidelines for the gradual introduction of different foods during the comple- Iron and Zinc mentary feeding period are based on cultural factors and food availability rather than scientific More than 90% of iron requirements during the evidence. Whilst in developing countries, the fo- complementary feeding period in a breastfed in- cus is still on providing adequate nutrients to fant must be provided by complementary foods.

Complementary Foods 103 Potential strategies for achieving this include the Vegetarian Diets use of fortified weaning foods, iron-fortified infant formulas and follow-on formulas, foods nat- If infants receive a vegetarian diet it is important urally rich in bioavailable iron such as meat, or that the diet includes a sufficient amount of milk the use of supplements. The most suitable strat- (about 500 ml/day) and dairy products. Vegan di- egy will vary in different circumstances. The ets should be discouraged in infancy because of same strategies may broadly be used to provide the risk of B12 deficiency which can affect neuro- an adequate supply of zinc – a particularly im- development. portant issue in developing countries where deficiencies are common. Cow’s milk is a very poor source of iron, and it is generally recommended Allergy that it should not be used as the main drink before 12 months of age. Certain foods, including egg, fish, nuts and seafood, are potentially allergenic. However, the evidence that delaying the introduction of Salt and Sugar such foods reduces the risk of developing food allergy is not currently convincing, even for in- High intakes of salt in infancy may be associated fants with a family history of atopy [6] . Further- with later higher blood pressure [4] . Further- more, the exclusion of fish – the richest natural more, infants may become accustomed to a salty source of n-3 fatty acids – and eggs from the taste which could affect subsequent food prefer- diet could itself have undesirable nutritional ences and intake. Hence it is generally agreed that consequences. salt should not be added to food during the complementary feeding period. Similarly, sugar is associated with the development of dental caries. Taste and Food Acceptance Its use should be restricted, and it is important to ensure good dental hygiene practices as early as An important but poorly researched area is the possible. potential effect of early diet on food acceptance and subsequent food preferences [7] . There may be ‘windows’ during infancy during which cer- Gluten tain tastes are more readily accepted. Children are predisposed to like high energy foods, to pre- For populations affected by celiac disease, the fer sweet and salty tastes and to reject new foods. risk may be reduced if small amounts of gluten However, these predispositions may be modified are gradually introduced while the infant is still by early dietary experience. Hence, parents play being breastfed. The risk of celiac disease is high- an important role in establishing good dietary er if gluten is given before 3 months, and delaying habits. exposure until 7 months or later may also increase the risk [5] . In genetically predisposed infants, both early ( ! 3 months) and possibly late Conclusions (6 7 months) introduction of gluten may be associated with a higher risk of developing type-1 • Complementary foods should not be intro- diabetes. duced before 17 weeks, but all infants should start complementary foods by 26 weeks

104 Pediatric Nutrition in Practice • It is important to ensure that complementary • In populations at risk of celiac disease, gluten foods provide adequate energy density (mini- should be gradually introduced while the in- mum 25% fat), and that the diet includes good fant is still being breastfed sources of protein, iron and zinc. Strategies • The complementary feeding period should be used to achieve this will vary in different en- regarded as an important time for establishing vironments good eating habits and food preferences. Sug- ar and salt should not be added to complementary foods

References

1 Agostoni C, Decsi T, Fewtrell M, et al; 4 Geleijnse JM, Hofman A, Witteman JC, allergy. Joint statement of the European ESPGHAN Committee on Nutrition: et al: Long-term effects of neonatal Society for Paediatric Allergology and Complementary feeding: a commen- sodium restriction on blood pressure. Clinical Immunology (ESPACI) Com-

tary by the ESPGHAN Committee on Hypertension 1997; 29: 913–917. mittee on Hypoallergenic formulas and Nutrition. J Pediatr Gastroenterol Nutr 5 Norris JM, Barriga K, Hofenberg EJ, et the European Society for Paediatric

2008; 46: 99–110. al: Risk of celiac disease autoimmunity Gastroenterology and Nutrition 2 Kramer MS, Kakuma R: The optimal and timing of gluten introduction in (ESPGHAN) Committee on Nutrition.

duration of exclusive breastfeeding: a the diet of infants at increased risk of Arch Dis Child 1999; 81: 80–84.

systematic review. Adv Exp Med Biol disease. JAMA 2005; 293: 2343–2351. 7 Skinner JD, Carruth BR, Bounds W,

2004; 554: 63–77. 6 Host A, Koletzko B, Dreborg S, et al: Ziegler PJ: Children’s food preferences: 2 3 WHO: The Optimal Duration of Exclu- Dietary products used in infants for a longitudinal analysis. J Am Diet

sive Breastfeeding. Report of an Expert treatment and prevention of food Assoc 2002; 102: 1638–1647. Consultation. Geneva, WHO, 2001.

Complementary Foods 105 Koletzko B. (ed): Pediatric Nutrition in Practice. Basel, Karger, 2008, pp 106–109

2 Nutrition of Healthy Infants, Children and Adolescents

2.5 Allergy Prevention through Early Nutrition Sibylle Koletzko

Key Words tion and allergic manifestations. Nutritional in- Tolerance induction ؒ Sensitization ؒ Allergen tervention aiming at a reduction in allergy risk -avoidance ؒ Breastfeeding ؒ Atopic dermatitis should be started early in infancy [1] . Data on al imentary allergy prevention were obtained in observational cohort studies, which describe asso- Key Messages ciations and can generate hypotheses, and in con- R Allergen contact during the first months of life trolled intervention studies which can prove modulates induction of tolerance and sensitization causal relationships. The available data do not to food antigens support the conclusion that maternal elimination R Nutritional intervention can reduce the risk of al- diets during pregnancy and lactation provide a lergic manifestations, particularly of atopic dermatitis and cow’s milk protein allergy during the first benefit for allergy risk reduction in the infant. year of life in children with a positive family history Data on breastfeeding effects on allergy are con- for allergy troversial. In infants with a positive family his- R Most data for allergy prevention through nutrition tory of allergy and who are not exclusively breast- are generated from epidemiological, observation- fed, the use of certain infant formulae based on al and intervention studies. While the first two types can describe associations and generate hy- hydrolyzed proteins reduces the risk of allergic potheses, only results from intervention studies manifestations. Delayed introduction of comple- can prove a causal relationship mentary feeding has no proven benefit. R The impact of breastfeeding on the risk of allergy is difficult to establish because randomized controlled intervention trials have not been performed Maternal Allergy Avoidance during for ethical reasons. Conclusions from observational cohort studies may not be valid due to selection Pregnancy and Lactation bias and reverse causality R Every hypoallergenic formula product should be Maternal dietary allergen exclusion during preg- evaluated because the degree of hydrolyzation or nancy has been proposed as a potential strategy source of protein alone do not predict effects to reduce allergy risk in the offspring, but the Copyright © 2008 S. Karger AG, Basel available data do not support any beneficial effects [2] . Human milk contains food antigens arising from cow’s milk, egg, wheat and other Introduction foods a few hours after maternal consumption of the respective foods. The concentration of cow’s Contact with food allergens in early infancy milk protein in breast milk is only 100,000 times modulates the development of tolerance to food lower than in cow’s milk itself, and does not cor- allergens, and also the development of sensitiza- relate with the amount of antigen ingested by the mother. Whether these low antigen amounts in often with non-randomized breastfed reference breast milk induce sensitization or tolerance is groups [7–10]. All published randomized trials not clear. In a randomized controlled trial, no were performed in infants with an increased beneficial effects of avoiding egg and milk con- atopic risk based on one parent or sibling affected sumption by lactating women was found on the by allergy, or both parents affected, or elevated development of children’s allergic disease until 5 cord blood IgE, or other criteria. Therefore, the years of age [3] . Maternal exclusion diets bear the results cannot be generalized to infants with non- risk of inadequate supply of certain nutrients. In atopic parents. Some of the studies included ad- the absence of beneficial evidence, maternal ex- ditional co-interventions, like maternal dietary clusion diets during pregnancy and lactation for or environmental restrictions, or delayed intro- allergy prevention are not recommended. duction of complementary feeding. The analysis of results in a recent Cochrane review led to the conclusion that there is limited Breastfeeding evidence for risk reduction of infant and childhood allergy and infant cow’s milk allergy with a Breastfeeding is preferred for infants after birth hydrolyzed formula, compared to a cow’s milk because of nutritional, immunological and psy- formula [11] . In this analysis, many studies even chological benefits. The potential allergy-preven- of high quality were excluded because of a drop- tive effect of exclusive or partial breastfeeding has out rate of 120%. However, it is highly question- 2 not been properly assessed because randomization able whether this exclusion criterion should be of breastfeeding is not possible for ethical consid- applied for infant feeding trials starting at birth, erations [4] . Mothers who exclusively breastfeed where it is highly likely that feeding intentions differ markedly from those who feed formula with expressed at the time of birth change over time regard to education, socioeconomic factors, smok- [12] . For this and other reasons the Cochrane re- ing, keeping pets at home, introduction of other view has been heavily criticized, and the conclu- foods, and many other factors which may influ- sions were challenged by an international panel ence the incidence of allergy. Inverse causality may of allergy experts [13] . play a role in non-randomized studies, i.e. mothers The German Infant Nutritional Intervention of infants with the highest degree of heredity or (GINI) study is by far the largest double-blind, signs of atopy within the first months of life may randomized controlled intervention trial in this tend to prolong exclusive and total breastfeeding area, and the only trial sponsored by a govern- [5] . Recent meta-analyses are not conclusive as to mental grant rather than industry funds [7, 9]. whether exclusive breastfeeding during the first The trial evaluated the allergy-preventive effects months of life or long duration of any breastfeed- of feeding during the first 4 months of life, in ad- ing are beneficial for reducing allergy risk [6] . dition to breastfeeding, three hydrolyzed formu- However, breastfeeding is strongly recommended lae compared to a cow’s milk formula in high-risk for all healthy infants regardless of atopic risk. infants. Among different atopic manifestations (atopic dermatitis, asthma, gastrointestinal manifestations, allergic rhinitis, urticaria), only the Feeding Hydrolyzed Infant Formulae risk of atopic dermatitis was reduced by hydrolyzed formula. Compared to cow’s milk formula, Several intervention trials evaluated infant for- an extensively hydrolyzed casein formula signifi- mulae based on partially or extensively hydro- cantly reduced atopic dermatitis (per protocol lyzed proteins compared to cow’s milk formula, and intention to treat analyses), and a partially

Allergy Prevention through Early Nutrition 107 % based on soy protein does not reduce allergy risk, 40 CMF pHF-W including food allergy [15] . eHF-W eHF-C 35 30 * 25 * Complementary Foods 20 * * 15 * 10 Most available data originate from large cohort 5 * studies. Very early solid food introduction within 0 the first 3–4 months of life, with a high variety of 0136 Age, years different foods, seems to increase the risk of eczema, and possibly also of food allergy [5, 16, 17]. Delaying the introduction of solid foods beyond Fig. 1. Cumulative incidence of the physician’s diagnosis of atopic dermatitis in 988 infants of the GINI interven- the 6th month of life has no protective effect and tion group, who were fed one of four study formulae dur- may even increase the risk for allergy [18] . This ing the first 4 months of life and were followed until 6 effect was also found for allergenic foods such as years of age (per protocol analysis). The allergy-preven- hen’s egg, cow’s milk, fish, and wheat [19, 20]. tive effect in infants fed the extensively hydrolyzed casein formula (eHF-C) and partially hydrolyzed whey for- Thus it is recommended that complementary mula (pHF-W) appeared in the first year of life and per- foods should not be introduced before the 17th sisted until 6 years, while the significant reduction in the week of life, but no later than the 26th week of life, extensively hydrolyzed whey formula (eHF-W) occurred regardless of the familial risk of allergy [21, 22] . in the 6th year only [8] . CMF = Cow’s milk formula.

Conclusions hydrolyzed whey formula significantly reduced atopic dermatitis (in the per protocol analysis • Maternal exclusion diet during pregnancy only). In contrast, the extensively hydrolyzed and lactation has no allergy-preventive effect whey formula was ineffective. The effect devel- and is not recommended oped in the 1st year of life and persisted until 6 • Exclusive breastfeeding for the first 4–6 years [8] ( fig. 1 ). months of life and continuous breastfeeding during gradual solid food introduction are recommended for all infants Protein Sources Other than Cow’s Milk in • In industrialized countries, solid food intro- Infant Feeding duction should be started not before the 17th and not later than the 26th week of life, re- The use of unmodified mammalian milk protein, gardless of the hereditary risk for allergy including unmodified sheep, buffalo, mare’s or • If infant formula is used during the first 6 goat’s milk, or unmodified soy or rice milk, is not months of life in infants with a family history recommended for infants because their composi- of allergy, a protein hydrolysate formula with tion is inadequate to serve as the sole food source documented reduced allergenicity should be for infants [14] . Moreover, these milks are not given recommended for infants with suspected or prov- • Formulations based on other milk proteins en cow’s milk protein allergy because of the risk (sheep, buffalo, mare’s or goat’s milk), as well of possible allergenic cross-reactivity. A recent as soy or rice protein have no allergy-preven- Cochrane review concluded that infant formulae tive effects and are not recommended

108 Pediatric Nutrition in Practice References

1 Koletzko S: Food allergen avoidance for 9 von Berg A, Koletzko S, Filipiak- 16 Schoetzau A, Filipiak-Pittroff B, Franke treatment and prevention; in Koletzko Pittroff B, Laubereau B, Gruebl A, K, Koletzko S, von Berg A, Gruebl A, S (ed): Food Allergy in Childhood. Wichmann HE, Bauer CP, Reinhardt D, Bauer CP, Berdel D, Reinhardt D, Wich- Causes and Consequences. Heilbronn, Berdel D: Certain hydrolyzed formulas mann HE: Effect of exclusive breast- SPS, 2007, pp 190–211. reduce the incidence of atopic dermati- feeding and early solid food avoidance 2 Kramer MS, Kakuma R: Maternal di- tis, but not of asthma: three year results on the incidence of atopic dermatitis in etary antigen avoidance during preg- of the GINI-Study. J Allergy Clin high-risk infants at 1 year of age. Pedi-

nancy or lactation, or both, for prevent- Immunol 2007, in press. atr Allergy Immunol 2002; 13: 234–242. ing or treating atopic disease in the 10 Halken S, Hansen KS, Jacobsen HP, 17 Filipiak B, Zutavern A, Koletzko S, von child. Cochrane Database Syst Rev Estmann A, Faelling AE, Hansen LG, Berg A, Brockow I, Grubl A, Berdel D,

2006; 3:CD000133. Kier SR, Lassen K, Lintrup M, Reinhardt D, Bauer CP, Wichmann HE, 3 Björkstén B: Allergy prevention. Inter- Mortensen S, Ibsen KK, Osterballe O, Heinrich J: Solid food introduction in ventions during pregnancy and early Host A: Comparison of a partially relation to eczema: results from a four- infancy. Clin Rev Allergy Immunol hydrolyzed infant formula with two year prospective birth cohort study. J

2004; 26: 129–138. extensively hydrolyzed formulas for Pediatr 2007; 151: 352–358. 4 Kramer MS, Kakuma R: The optimal allergy prevention: a prospective, 18 Zutavern A, Brockow I, Schaaf B, von duration of exclusive breastfeeding: a randomized study. Pediatr Allergy Berg A, Diez U, Borte M, Kraemer U,

systematic review. Adv Exp Med Biol Immunol 2000; 11: 149–161. Herbarth O, Behrendt H, Wichmann

2004; 554: 63–77. 11 Osborn DA, Sinn J: Formulas contain- HE, Heinrich J: Timing of solid food 5 Zutavern A, Brockow I, Schaaf B, Bolte ing hydrolysed protein for prevention introduction in relation to eczema, G, von Berg A, Diez U, Borte M, Her- of allergy and food intolerance in asthma, allergic rhinitis, and food and barth O, Wichmann HE, Heinrich J: infants. Cochrane Database Syst Rev inhalant sensitization at the age of 6

Timing of solid food introduction in 2006; 4:CD003664. years: results from the Prospective relation to atopic dermatitis and atopic 12 Fewtrell M, Kennedy K, Singhal A, Birth Cohort Study LISA. Pediatrics 2

sensitization: results from a prospec- Martin RM, Ness A, Hadders-Algra M, 2008; 121:e44–e52.

tive birth cohort study. Pediatrics 2006; Koletzko B, Lucas A: How much loss to 19 Poole JA, Barriga K, Leung DY, Hoff-

117: 401–411. follow-up is acceptable in long-term man M, Eisenbarth GS, Rewers M, Nor- 6 Kramer MS, Kakuma R: Optimal dura- randomised trials and prospective ris JM: Timing of initial exposure to tion of exclusive breastfeeding. studies? Arch Dis Child 2008, in press. cereal grains and the risk of wheat al-

Cochrane Database Syst Rev 2002; 1: 13 Host A, Halken S, Muraro A, Dreborg lergy. Pediatrics 2006; 117: 2175–2182. CD003517. S, Niggemann B, Aalberse R, Arshad 20 Kull I, Bergstrom A, Lilja G, Pershagen 7 von Berg A, Koletzko S, Grubl A, SH, von Berg A, Carlsen KH, Duschen G, Wickman M: Fish consumption dur- Filipiak-Pittroff B, Wichmann HE, K, Eigenmann PA, Hill D, Jones C, Mel- ing the first year of life and develop- Bauer CP, Reinhardt D, Berdel D: The lon M, Oldeus G, Oranje A, Pascual C, ment of allergic diseases during child-

effect of hydrolyzed cow’s milk formula Prescott S, Sampson H, Svartengren M, hood. Allergy 2006; 61: 1009–1015. for allergy prevention in the first year Wahn U, Warner JA, Warner JO, Van- 21 ESPGHAN Committtee on Nutrition; of life: the German Infant Nutritional denplas Y, Wickman M, Zeiger RS: Agostoni C, Decsi T, Fewtrell M, Goulet Intervention Study, a randomized Dietary prevention of allergic diseases O, Kolacek S, Koletzko B, Michaelsen double-blind trial. J Allergy Clin in infants and small children. Pediatr KF, Moreno L, Puntis J, Rigo J, Shamir

Immunol 2003; 111: 533–540. Allergy Immunol 2008; 19: 1–4. R, Szajewska H, Turck D, van Gou- 8 von Berg A, Filipiak-Pittroff B, Kramer 14 Koletzko B, Baker S, Cleghorn G, Neto doever J: Complementary feeding. J

U, Link E, Bollrath C, Brockow I, UF, Gopalan S, Hernell O, Hock QS, Pediatr Gastroenterol Nutr 2008; 46: Koletzko S, Gruebl A, Heinrich J, Jirapinyo P, Lonnerdal B, Pencharz P, 99–110. Wichmann HE, Bauer C, Reinhardt D, Pzyrembel H, Ramirez-Mayans J, 22 Greer FR, Sicherer SH, Burks AW: Berdel D; GINIplus Study Group: Pre- Shamir R, Turck D, Yamashiro Y, Zong- Effects of early nutritional interven- ventive effect of hydrolyzed infant for- Yi D: Global standard for the composi- tions on the development of atopic dis- mulas persists until age 6: long-term tion of infant formula: recommenda- ease in infants and children: the role of results from the German Infant Nutri- tions of an ESPGHAN coordinated maternal dietary restriction, breast- tional Intervention Study GINI. J international expert group. J Pediatr feeding, timing of introduction of com-

Allergy Clin Immunol 2008, in press. Gastroenterol Nutr 2005; 41: 584–599. plementary foods, and hydrolyzed for-

15 Osborn DA, Sinn J: Soy formula for pre- mulas. Pediatrics 2008; 121: 183–191. vention of allergy and food intolerance in infants. Cochrane Database Syst Rev

2004; 3:CD003741.

Allergy Prevention through Early Nutrition 109 Koletzko B. (ed): Pediatric Nutrition in Practice. Basel, Karger, 2008, pp 110–113

2 Nutrition of Healthy Infants, Children and Adolescents

2.6 Toddlers, Pre-School and School Children H i l d e g a r d P r z y r e m b e l

Key Words increase both the frequency and variety of social Food-based dietary guidelines ؒ Dietary habits ؒ contacts outside the home and thereby food and . [Food preference ؒ Food choice ؒ Feeding skills ؒ meal choices [1 Meals A healthy diet for children should be devised on the basis of both scientific and practical considerations. Scientific criteria are the adequacy of Key Messages the intake in comparison to recommendations R Toddlers and children should participate in family for energy and nutrient intake to support normal meals development and growth, taking into account the R Toddlers do not need specially prepared commercial foods for particular nutritional uses. The use of preventive effects of an adequate diet on chronic such meals is determined by convenience diseases of adulthood [2] . Practical criteria are re- R Food-based dietary guidelines for children should gional or national dietary habits, availability and name basic food groups, give approximate cost of foods, and taste preferences of children. amounts to be consumed and provide exemplary Food-based dietary guidelines for children recipes according to local habits have been devised. As an example the so-called R Nutrient supplements and fortified foods should be used only when indicated optimised mixed diet (OptimiX) [3] developed in R Beverages of no or low energy content should ac- Germany is described. Such guidelines can be company meals Copyright © 2008 S. Karger AG, Basel easily adapted to different typical eating habits, meal schedules and differences in locally available basic foods. They are based on commonly available foods to be prepared at home, but leave Introduction room for the integration of ready-to-eat products and foods preferred by many children, like ‘fast The age range of 1 to approximately 12 years foods’ and sweets. includes very different phases of development. With increasing motor skills, toddlers, some of whom are still partly breastfed, continue to feed Principles of Children’s Diets and Eating themselves with an increasing variety of foods as part of the family diet. Food preferences devel- Food-based dietary guidelines, based on the en- oped in the first year of life tend to persist but are ergy and nutrient needs of children and their modified under the influence of parents, siblings preferences and on health aspects, provide advice and play mates. Pre-school and school children on food selection, meal composition and meal Table 1. Adequate food consumption amounts according to age

Recommended foods Age, years (≥80% of energy intake) 1 2–3 4–6 7–9 10–12

Generous amounts Beverages, ml/day 600 700 800 900 1,000 Bread, cereal (flakes), g/day 80 120 170 200 250 Potatoes, pasta, rice, cereals, g/day 80 100 120 140 180 Vegetables, g/day 100 120 180 200 230 Fruit, g/day 100 120 180 200 230 Moderate amounts Milk, milk products, ml or g/day 300 330 350 400 420 Meat, meat products, g/day 30 35 45 55 65 Eggs, number/week 1–2 1–2 2 2 2–3 Fish, g/week 50 70 100 150 180 Small amounts Margarine, oil, butter, g/day 15 20 25 30 35

Tolerated foods Age group (≤20% of energy intake) toddlers, schoolchildren adolescents 2 Cake, sweets, g/day <50 <80 Jam, sugar, g/day <10 <20

Modified from Kersting et al. [3].

patterns, including recipes. The main food groups within a food group, e.g. instead of milk and milk included are of high nutrient density: cereals and products cheese can be consumed based on other starchy foods (bread, pasta, potatoes, etc.); equivalency in the calcium content (100 ml milk vegetables, legumes and fruits; milk and dairy corresponds to about 15 g of hard and 30 g of soft products; meat, poultry, eggs and (oily) fish; and cheese). The amounts in table 1 need not be con- fats and oils. sumed every day, the aim should be the average A list of reference amounts of the main food amount per week. Variability in daily intake is groups which provide 1 80% of the appropriate normal and should be tolerated; the variability of energy intake and 100% of all nutrients is part of daily energy intakes of children can be 50% OptimiX [3] ( table 1 ). In addition, less than 20% around the average. Moreover, small and inactive of the energy intake is provided by ‘tolerated’ children will eat smaller amounts than active and food groups, often of low nutrient but high en- big children, and boys will consume more than ergy density. These foods are not prohibited, but girls of the same age. Children should be allowed permitted to meet, e.g., the sweet preferences of from the start to determine the amounts they some children and to permit flexibility in the wish to eat and not be forced to empty their plates. composition of meals. The amounts of foods are This will permit them to eat to satiety and help to guidance values, with the possibility to choose avoid overnutrition and overweight.

Toddlers, Pre-School and School Children 111 Recommended Diet Composition Choice of Foods

OptimiX provides about 54% of the energy in- Foods particularly manufactured and specially take from mostly complex carbohydrates, 32% of fortified with nutrients are not a necessary part energy from fat of mostly plant origin and 14% of of a healthy toddler’s diet, although a wide vari- energy from protein, half of animal and half of ety of such foods is available and is convenient to plant origin. The most suitable fat intake of tod- use. In circumstances where nutrient-dense foods dlers is not known; it should not be less than 25% are scarce, fortification or supplementation can, of energy [2, 4, 5] . Protein sources will reflect however, become necessary, particularly with re- country- and culture-specific dietary habits, and gard to iron, iodine, zinc and calcium. plant protein can provide the majority of protein Self-prepared food for toddlers should not be intake. In that case a variety of plant foods should salted. Varieties of processed foods with a low- be consumed, which compensate for each other’s salt content should be chosen. deficiencies in certain indispensable amino ac- Bread and cereals, but also rice and pasta ids. A vegan diet with no animal-derived food is should preferably be wholegrain products which not suitable for toddlers. contain B vitamins, magnesium, iron, fiber, protein and unsaturated fatty acids. A mixture of wholegrain and more refined products may be Meals and Meal Patterns better accepted by young children. Vegetables and fruits, if not served raw, should Whenever possible, meals should be consumed be boiled as briefly and in as little water as pos- in the company of others and at regular times, sible to reduce inevitable losses of vitamins, min- while snacking should be avoided. The distribu- erals and secondary plant substances, like carot- tion of the basic and tolerated foods over differ- enoids, phytosterins, polyphenols. While the pri- ent meals can vary, but all meals together add up mary choice of both fruit, legumes and vegetables to provide an adequate intake of all nutrients and should be those which are in season, it may be energy. Toddlers will need more frequent meals necessary to be more flexible in the case of strong than older children. The type of meals, both hot dislikes. Fruit juices can substitute for fruit in ex- and cold, and the time of day at which they are ceptional cases. consumed will vary between countries and fam- Milk and dairy products are indispensable in ilies. Both cold and hot meals should be accom- all children’s diets as sources of calcium and oth- panied by a beverage. Cold meals will mostly er minerals as well as vitamins. From the age of 2 consist of bread and cereals, dairy products and years full-fat milk products can be replaced by raw fruit and vegetables and thus provide the reduced-fat products. majority of the daily carbohydrate, fiber and cal- Meat and meat products are important be- cium intake besides significant percentages of vi- cause of the well-available iron and zinc, particu- tamin C and folate intake. Hot meals are based larly for toddlers and young children. Moreover, on potatoes, rice or pasta, vegetables and salads, they provide high-quality protein and important while meat or fish serve as a supplement and B vitamins. Products low in fat should be pre- need not be eaten every day of the week. Hot ferred. Heme iron also increases the absorption meals thus contribute significantly to the intake of iron from plant food. of numerous vitamins and minerals, like vita- Fish is an important source of iodine and min B 6 and B 12, magnesium, phosphorus and io- long-chain n-3 fatty acids and should be eaten at dine. least once a week. Many children only accept

112 Pediatric Nutrition in Practice braised and fried fish, which might be high in of sugar and are unsuitable for relief of thirst. fat. Sugar-sweetened beverages tend to be overcon- To increase the quality of the fat consumed, at sumed, which can result in a positive energy bal- least half of the total fat intake, both ‘hidden’ and ance and finally overweight [6–8] . visible, should come from plant oils, preferably those with a high content of mono- and polyunsaturated fatty acids and which contain some ␣ - Conclusions linolenic acid (rape seed, soy, flaxseed) and sufficient vitamin E. These oils are practically free of • Dietary recommendations for toddlers (1–3 trans fatty acids. An overall low fat use will fur- years) gradually approach those for children, ther reduce the total intake of saturated and trans adolescents and adults; the percentage of en- fatty acids. ergy derived from fat should decrease from Beverages should preferably be offered to tod- 1 40% to around 30% dlers from a cup and should be free of or low in • Children should be permitted (within reason- energy (water or unsweetened herbal or fruit able limits) to determine the amount of food teas). Milk is not to be regarded as a beverage but they consume from a range of basic food as a food. Fruit juices can contain valuable vita- groups mins and minerals, but, if undiluted, are high in • Preferences for taste should be respected to a sugars ( 1 10% of weight). Fruit-based and cola certain degree 2 beverages also often contain generous amounts

References

1 Young EM, Fors SW, Hayes DM: Asso- 4 Agostoni C, Decsi T, Fewtrell M, Goulet 6 Kranz S, Smiciklas-Wright H, Siega-Riz ciations between perceived parent be- O, Kolacek S, Koletzko B, Michaelsen AM, Mitchell AD: Adverse effect of haviors and middle school student fruit KF, Moreno L, Puntis J, Rigo J, Shamir high added sugar consumption on di- and vegetable consumption. J Nutr R, Szajewska H, Turck D, Van Goudo- etary intake in American preschoolers.

Educ Behav 2004; 36: 2–8. ever J; ESPGHAN Committee on Nutri- J Pediatr 2005; 146: 105–111. 2 Gidding SS, Dennison BA, Birch LL, tion: Complementary feeding: a com- 7 Ludwig DS, Peterson KE, Gortmaker Daniels SR, Gilman MW, Lichtenstein mentary by the ESPGHAN committee SL: Relation between consumption of AH, Rattay KT, Steinberger J, Stettler on nutrition. J Pediatr Gastroenterol sugar-sweetened drinks and childhood

N, Van Horn L; American Heart Asso- Nutr 2008; 46: 99–110. obesity. Lancet 2001; 357: 505–508. ciation: Dietary recommendations for 5 Hilbig A, Kersting M: Effects of age and 8 Welsh JA, Cogswell ME, Rogers S, children and adolescents: a guide for time on energy and macronutrient Rockett H, Mei Z, Grummer-Strawn

practitioners. Pediatrics 2006; 117:544– intake in German infants and young LM: Overweight among low-income 559. children: results of the DONALD study. preschool children associated with the

3 Kersting M, Alexy U, Clausen K: Using J Pediatr Gastroenterol Nutr 2006; 43: consumption of sweet drinks: Mis-

the concept of Food Based Dietary 518–524. souri, 1999–2002. Pediatrics 2005; 115: Guidelines to develop an Optimized e223–e229. Mixed Diet (OMD) for German children and adolescents. J Pediatr Gastro-

enterol Nutr 2005; 40: 301–308.

Toddlers, Pre-School and School Children 113 Koletzko B. (ed): Pediatric Nutrition in Practice. Basel, Karger, 2008, pp 114–117

2 Nutrition of Healthy Infants, Children and Adolescents

2.7 Adolescence Luis A. Moreno

Key Words In adolescents, energy and nutrients are re- Adolescence ؒ Eating patterns ؒ Nutrient intake ؒ quired not only for the maintenance of normal Energy and nutrient requirements ؒ Dietary function and body stores, but also for growth and guidelines development. Growth velocity differs with age, with the highest growth rates occurring during the first 2 years of life and during puberty. Ado- Key Messages lescence is a nutritionally vulnerable develop- R Adolescence is a nutritionally vulnerable period mental stage because growth rate accelerates, and because of an accelerated growth rate and in- amplified caloric and global nutrition needs due creased nutrient needs to pubertal growth stimulate appetite. R Adolescent’s nutritional status should be assessed on an individual basis, using information from clin- All adolescents should have access to a safe ical, biochemical, anthropometric, dietary and psy- and adequate food supply that promotes optimal chological assessments physical, cognitive, social and emotional growth R The diet should be based on fruits and vegetables, and development. As some chronic diseases of whole grains, dairy products, beans, fish and lean adulthood begin during childhood and adoles- meat R Calorie-dense foods and beverages with minimal cence, an optimal nutrition approach should be content of essential nutrients should return to their considered for recommendations focusing on role as occasional discretionary items in an other- adolescents, and this is a way to try to respond to wise balanced diet the obesity epidemic that has recently emerged Copyright © 2008 S. Karger AG, Basel [2, 3] .

Introduction Eating Patterns

Adolescence is the period from puberty to the As children grow up, diversification in sources of stage of complete body maturation. Puberty can food and influences on eating behavior occur. be defined as a maturational process of the hy- Social constraints on families may necessitate the pothalamus-pituitary-gonadal axis resulting in presence of multiple caregivers, eating out, and growth and development of the genital organs frequent fast food consumption. Many adoles- and, concomitantly, in physical and psychologi- cents, because of parental work schedules, are cal changes towards adulthood leading to the ca- alone at home and prepare their own snacks and pacity to reproduce [1]. meals. By early adolescence, peer pressure begins to substitute for parental authority. Very often, assuming protein use for growth is comparable meals and snacks are routinely obtained outside with maintenance data for adults. Because of home, without any supervision. Adolescents of- wide variability in growth rates, physical activity ten have discretionary funds to use for self-select- and metabolic rate, it is difficult to estimate speed foods. Current eating patterns do not resemble cific nutrient requirements for adolescents. For the typical pattern of providing at least breakfast, practical reasons, dietary reference intakes (DRIs) dinner and a single snack at home, with lunch at for adolescents are categorized by chronological school [4] . Sweetened beverage intakes contribute age rather than maturational development. Thus, significantly to total caloric intake, and snacks health professionals should use them with cau- often contribute to excess consumption of discre- tion, particularly in individual assessments. An tionary calories and displace foods containing adolescent’s nutritional status should be assessed essential nutrients [5] . Parallel to the psychoso- on an individual basis, using information from cial transition from dependence on parental au- clinical, biochemical, anthropometric, dietary thority to independent thought processes, food and psychosocial assessments. There is no clear choices and purchases are increasingly made by consensus on dietary recommendations for ado- the adolescent. Peer pressure for conformity, in lescents [7] , but some accepted general ideas are part driven by media promotion of fast food di- described below. rectly to teens, contributes to overeating. Paren- tal role modeling is important in establishing ad- 2 olescents’ food choices; depending on their own Energy food choices, parents can be either positive or negative role models [6] . The DRI values for energy at various chronologi- Currently, many adolescents have a high in- cal ages and for both sexes are shown in Chapter take of sweetened beverages, French fries, pizza, 4.2. The DRI for energy do not include a safety and hamburgers, with a concomitant low intake factor for increased energy needs (illness, trau- of fruits, vegetables, dairy products, whole grains, ma, stress) and are considered to be only average lean meats and fish. The described eating pattern needs. Needs for adolescents will vary with phys- results in consumption of excess fat, saturated ical activity and stage of maturation. fat, trans fat, and added sugars along with insufficient consumption of micronutrients such as calcium, iron, zinc, and potassium, as well as vi- Protein tamins A, D, C and folic acid [5] . During adolescence, protein needs are related more closely to the growth pattern than to chron- Growth as a Basis for Nutritional ological age. Average intakes of protein in adoles- Requirements cents are generally well above the DRI. However, protein metabolism is particularly sensitive to There is a lack of specific scientific evidence on energy restriction in adolescents during pubertal which to base the nutrient needs of adolescents. growth and maturation. Current dietary patterns The recommended daily allowances (RDAs) for of adolescent girls that result in restricted energy energy are based on median energy intakes of ad- intakes represent potential health problems when olescents followed in longitudinal growth stud- protein sources are used to meet energy needs. ies. RDAs for protein in this group are calculated The DRI for protein by chronological age are from growth rates and body composition data, shown in Chapter 4.2.

Adolescence 115 Minerals Zinc

All mineral needs increase during adolescence. Zinc is known to be essential for growth and sex- Adolescents at the peak of their growth velocity ual maturation, and retention of zinc increases will require large quantities of nutrients. For during puberty. Limited intake of zinc-contain- some minerals, like calcium, iron and zinc, low ing foods may affect physical growth as well as intakes are often the result of the current food the development of secondary sex characteristics choices of adolescents. DRI for minerals are [9] . shown in Chapter 4.2.

Vitamins Calcium The need for vitamins is also increased during Given the accelerated muscular, skeletal and en- adolescence. Because of increased energy de- docrine development, calcium needs are greater mands, thiamin, riboflavin and niacin are re- during puberty and adolescence than in child- quired in increased quantity for the release of en- hood or the adult years. In fact, 45% of the skel- ergy from carbohydrates. With great tissue syn- etal mass is added during adolescence. The DRI thesis, there is an increased demand for vitamins for calcium is 1,300 mg/day in all adolescents. B6 and B12 . There are also increased requirements Adequate intake for calcium cannot be met with for vitamin D (for rapid skeletal growth) and vi- dairy-free diets while meeting other nutrient rec- tamins A, C and E are needed for new cell growth. ommendations [8] . Calcium requirements are The DRIs for vitamins are shown in Chapter expressed as adequate intakes (AIs). The AIs ad- 4.2. dress the needs of all individuals in a group, but lack of data or uncertainty in the data prevent being able to specify with confidence the percent- Conclusions age of people covered by this intake. • Diet should primarily rely on fruits and vegetables, whole grains, dairy products, beans, Iron fish and lean meat • Low intakes of saturated and trans fat, choles- During adolescence, iron requirements are in- terol and added sugar and salt should be pro- creased. In boys, this increase reflects not only moted the expanding blood volume, but also a rise in • Foods that are rich in essential nutrients (e.g. hemoglobin concentration that occurs with sex- calcium, iron) and that provide high amounts ual maturation. In girls, menstruation typically of dietary fiber and n-3 fatty acids should be starts about 1 year after peak growth. In girls emphasized with marginal dietary iron intakes and increased • Energy intake and physical activity should be menstrual blood losses, iron-deficiency anemia appropriate for the maintenance of a normal may result. Conversely, iron-deficiency anemia weight for height may be a limiting factor for growth during ado- • Calorie-dense foods and beverages with min- lescence. imal nutritional content must return to their role as occasional discretionary items in an otherwise balanced diet

116 Pediatric Nutrition in Practice References

1 Delemarre-van de Waal HA: Regula- 4 Moreno LA, Kersting M, de Henauw S, 7 Prentice A, Branca F, Decsi T, et al: tion of puberty. Best Practice Res Clin et al: How to measure dietary intake Energy and nutrient dietary reference

Endocrinol Metab 2002; 16: 1–12. and food habits in adolescence? – the values for children in Europe: method- 2 Gidding SS, Dennison BA, Birch LL, et European perspective. Int J Obes Relat ological approaches and current nutri-

al; American Heart Association: Di- Metab Disord 2005; 29(suppl 2):S66– tional recommendations. Br J Nutr

etary recommendations for children S77. 2004; 92(suppl 2):S83–S146. and adolescents: a guide for practitio- 5 Bowman SA, Gortmaker SL, Ebbeling 8 Gao X, Wilde PE, Lichtenstein AH,

ners. Pediatrics 2006; 117: 544–559. CB, et al: Effects of fast-food consump- Tucker KL: Meeting adequate intake for 3 Moreno LA, Mesana MI, Fleta J, et al; tion on energy intake and diet quality dietary calcium without dairy foods in AVENA Study Group: Overweight, obe- among children in a national house- adolescents aged 9 to 18 years (National

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Ann Nutr Metab 2005; 49: 71–76. 6 Neumark-Sztainer D, Hannan PJ, Story 106: 1759–1765. M, et al: Family meal patterns: associa- 9 Thompson P: Zinc status and sexual tions with sociodemographic charac- development in adolescent girls. J Am

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Adolescence 117 Koletzko B. (ed): Pediatric Nutrition in Practice. Basel, Karger, 2008, pp 118–121

2 Nutrition of Healthy Infants, Children and Adolescents

2.8 Challenges in Transition from Childhood to Adult Age in Low Income Populations Mauro Fisberg ؒ Marcia Vitolo ؒ Mara Andréa Valverde

Key Words is accelerated and this has an important effect on Nutritional habits ؒ Adolescence ؒ Nutritional nutritional needs and recommendations. At this deficiencies ؒ Obesity ؒ Nutritional disorders age, many nutritional problems arise and become prevalent: inadequate growth patterns, anemia, excess weight and some situations that could in- Key Messages directly affect nutritional balance, such as sports, R Adolescence is a period with many nutritional is- stress, menarche, etc. sues due to behavioral, physical and emotional Adolescents are prone to very different eating modifications patterns based on these modifications [1]. The R There is a major increase in eating disorders and various influences that could lead to inadequate excess weight in adolescents all over the world R Food selection is peer-influenced and adolescents food behaviors are peers, school, media, family are prone to receive feeding information by com- and environment. Body changes and final forma- munication sector and media tion of our personality are the main frames for R Obesity is increasing based on sedentary habits food intake at this age. Economic stance may in- and inadequate food selection fluence the development of food habits and gen- R Growth, maturation, physical and emotional modifications determine nutritional needs that can be erate nutritional problems [2]. poorly matched by food selection in teenagers. Healthy feeding is part of the global challenge Anemia, vitamin and zinc deficiency must be evalu- of a healthy lifestyle, especially in low income ated even in populations of a high economic level groups. Increasing physical activity and reducing Copyright © 2008 S. Karger AG, Basel sedentary life styles is of key importance in the prevention of chronic diseases and morbidity. Here we present some advice for healthy living: Introduction Good nutrition is part of a good life. Adolescence is characterized by several com- Adolescence is characterized by the World Health plex changes in the social, psychological, and Organization as the period from 10 to 20 years of physical roles of the individual, including also a age. During this period the adolescent will ac- marked growth spurt. During the transitional quire individual characteristics of differentia- phase from childhood to adolescence, interaction tion, and experience growth, and physical and with the reality outside the family and home in- sexual development. During adolescence growth creases, with specific nutritional challenges. Diseases of deprivation, mainly protein-ener- tary behavior, inadequate family habits, unsatis- gy malnutrition, are still a major public health factory food, excessive dietary fat and sugar in- problem in many parts of the world, despite the take, rapid eating, unbalanced snacks, and the technological development reached by mankind frequent consumption of sweets and candies. in the last centuries. Although present all over Obesity in childhood and adolescence induces the world, these diseases are particularly preva- metabolic changes such as dyslipidemia, insulin lent in developing countries and especially in the resistance and hypertension already at an early less favored layers of the population: they are age. Childhood obesity also bears a high risk of frequently associated with other forms of nutri- persistence into adult life, with an associated in- tional deficiencies, such as anemia and hypovita- creased risk of atherosclerotic disease, hyperten- minosis [3]. When fighting malnutrition, foods sion, metabolic disorders, and early mortality. specifically designed with trace element supple- Considering that 70% of the obese adolescents mentation may enhance nutritional recovery at become obese adults, and that child obesity is as- lower costs to the society. Anemia, vitamin A and sociated with a high morbidity and mortality lat- zinc deficiencies could be resolved by food sup- er in later life, the current increase in the preva- plementation in adolescents with no regular ac- lence of child obesity is most disturbing. In many cess to adequate food staples. populations the frequency of obesity is markedly Income commands the possibility of acquir- higher in less educated and poorer families. Also ing and using the goods and services that are es- in the Brazilian population, an inverse relation- 2 sential to maintain a good health status, includ- ship between the prevalence of obesity and socio- ing food, housing, clothing and sanitation. In less economic status is observed, similar to findings developed countries, typical problems of poverty, in developed countries [4]. Thus, the obesity epi- such as malnutrition, anemia and food depriva- demic may widen even further the existing in- tion, occur together with problems that are char- equalities in health and quality of life between acteristic of a modern life, such as the increasing the rich and poor parts of the population. prevalence of cardiovascular diseases, stress, Food in this transitional period of adolescence obesity, among others [4]. has many meanings. Even though adolescents At the same time, all over the world there is a need an adequate and balanced diet with an in- major increase in eating disorders in children creasing need for iron, vitamins and mineral salts and adolescents. From the social point of view, for normal growth and development, they look the beauty standards adopted mainly by women for a quick, modern meals that can identify them (and encouraged by men) may enhance the devel- with the group, such as the typical fast food or opment of eating disorders, since fashion clearly junk food [5]. The frequent consumption of those determines rules of thinness that are incompati- quick meals, snacks, and soft beverages can im- ble with adequate nutrition. The development of balance the daily diet. A large amount of fats and eating disorders in the population has been in- an excess of sugars contribute to the increase in tensified by standards in which ‘thin’ means ele- obesity observed in adolescents in many coun- gance and sensuality. The media are a catalyzing tries, including Brazil. agent of this trend, considerably influencing the After puberty, specific nutritional needs per- population and mainly female adolescents. sist. Adolescents need a higher ratio of many es- Among all nutritional disorders, obesity pre- sential nutrients to total energy intake than adults sents the highest increase in prevalence, not only to satisfy growth needs and the formation of lean in aff luent but also in developing countries. Many tissues [3]. When growth ceases and maximum inadequate lifestyle factors favor obesity: seden- height is reached, the larger bone mineralization

Challenges in Transition from Childhood to Adult Age in Low Income Populations 119 and body maintenance still carry a higher need important for adolescents to complete their lin- for many nutrients than in childhood. The phys- ear growth peak, even if the deposition of that iological changes associated with reproduction mineral continues for one more decade. Milk and capabilities may also change the needs for some milk products (preferably with a reduced milk fat nutrients, such as iron for girls after menarche content) are an excellent source of bioavailable and during pregnancy. calcium [8]. Some health problems of adolescents are close- Food should be tasty and appealing because ly related to nutrition. Many of the underlying eating is one of the great pleasures in life. Health- factors in the development of a non-healthy ado- care professionals can show adolescents that they lescent arise from social factors including, among do not need to stop eating the food they like, and others, poverty and unemployment, sexual or that, sometimes, with small changes in their ethnic prejudice, and the repercussions of social meals, they can reconcile the pleasure of eating changes within families and society. Social in- with group acceptance, having a healthy meal equalities may overwhelmingly interfere with the that will provide them with the so desired ap- nutrition of the individual. However, during pearance and performance. Fruit, legumes, veg- childhood and adolescence, the family aspect is etables, and grains (rice, corn, oat, and rye) should critical for correction and prevention of risk fac- be the basis of a healthy meal. Meals with rice and tors and nutritional disorders. beans, vegetables, legumes, fruit, and a moderate Many factors determine food habits and may amount of lean meat and dairy products, are influence adolescents, such as family, peers, healthy and balanced. Special attention should teachers, media and advertisements. It is very im- also be given to the amount eaten [9]. portant for health professionals to understand One should also prevent, alert or detect as ear- these influences and to modify deleterious infor- ly as possible any possible risk behaviors in the mation. diet that may lead to food disorders, such as an- A nutritionally adequate diet is important and orexia, bulimia and eating compulsively. should provide the energy and nutrients to sustain the adolescent growth spurt, the changes in body composition that take place during this pe- C o n c l u s i o n s riod, and appropriate physical activity [6]. It is recommended that fats be consumed in • Promote regular physical activity: sports and moderation, mainly saturated fats from foods of active leisure animal origin. Recommendations for a high di- • Support regular meal times etary fiber content and a lower fat intake gener- • Discourage meals in front of the TV ally do not have untoward effects on the energy • Drink plenty of liquids (preferably water!), but and nutrient supply. Whenever necessary, health avoid soft drinks/sugared beverages professionals should advise adolescents to limit • Avoid frequent eating of sweets and fatty foods the intakes of fat and enhance the dietary fiber (e.g. fried foods and snacks); give preference to intake, and promote physical activity and healthy cooked or baked foods over fried foods life habits for the wellbeing of the population • Promote the regular and daily eating of fruits [7]. and vegetables (e.g. include vegetables in prep- The marked increase in bone mass during ad- aration of sandwiches) olescence requires a sufficient calcium supply. Approximately half of the adult bone structure is deposited during adolescence. Dietary calcium is

120 Pediatric Nutrition in Practice References

1 Grigg M, Bowman J, Redman S: Disor- 4 Monteiro CA, Mondini L, Medeiros 7 National Center For Health Statistics: dered eating and unhealthy weight re- SAL, Popkin BM: The nutrition transi- Prevalence of Overweight among Chil-

duction practices among adolescent tion in Brazil. Eur J Clin Nutr 1995; 49: dren and Adolescents: United States,

females. Prev Med 1996; 25: 748–756. 105–113. 1999. http://www.cdc.gov/nchs/prod- 2 Neumark-Sztainer D, Palti H, Butler R: 5 Must A: Morbidity and mortality asso- ucts/pubs/pubd/hestats/overweight99. Weight concerns and dieting behaviors ciated with elevated body weight in htm/ Accessed August 2006. among high school girls in Israel. J Ad- children and adolescents. Am J Clin 8 Neutzling MB, Taddei JAAC, Rodrigues

olesc Health 1995; 16: 53–59. Nutr 1996; 63(suppl):4445S–4447S. EM, Sigulem DM: Overweight and obe- 3 Rodrigues AM, Cintra IP, Fisberg M: 6 National Center For Health Statistics: sity in Brazilian adolescents. Int J Obes

Avaliação do estado nutricional, pre- Prevalence of Overweight and Obesity Relat Metab Disord 2000; 24: 869–874. valência de sintomas de anorexia e bu- among Adults: United States, 1999. 9 Popkin BM, Doak CM: The obesity epi- limia nervosa e percepção corporal de http://www.cdc.gov/nchs/products/ demic is a worldwide phenomenon.

modelos adolescentes brasileiras. Rev pubs/pubd/hestats/obese/obese99.htm/ Nutr Rev 1998; 56: 106–114.

Nutr Brasil 2005; 4: 182–187. Accessed August 2006.

Challenges in Transition from Childhood to Adult Age in Low Income Populations 121 Koletzko B. (ed): Pediatric Nutrition in Practice. Basel, Karger, 2008, pp 122–124

2 Nutrition of Healthy Infants, Children and Adolescents

2.9 Food Choices, Cultural Influences and Nutrition Transition – A Japanese Perspective Yuichiro Yamashiro

Key Words in many parts of the world in the last few decades, Food culture ؒ Dietary habits ؒ Fast food ؒ Obesity ؒ showing us that food culture is quite fragile. This Metabolic syndrome has brought serious health problems to all genera- tions, including children and adolescents.

Key Messages R There is a powerful link between parenting and Past children’s obesity risk behaviors R Parents can help their children learn healthy habits Japanese women and men both enjoy the highest by modeling active and healthy eating behaviors, levels of longevity and healthy life expectancy in by making healthy meals, and by encouraging physical activity the world [1] . One of the main reasons for this fact R Discussions on the importance of traditional foods is the traditional Japanese food culture, which between parents and children are recommended consists of a high consumption of fish, complex R Establishing healthy habits becomes more effec- carbohydrates including dietary fiber, and a vari- tive when supported by healthcare practitioners ety of protein sources including soybean [2] . Copyright © 2008 S. Karger AG, Basel

Transition to the Current Clash of Cultures Introduction regarding Traditional and Global Foods

Food choices are strongly influenced by the cul- Over the last few decades in Japan, economic de- ture of one’s community and country, or what is velopment, accompanied by internationalization known as ‘food culture’. Food culture is created by and the infiltration of foreign cultures, has led to a long tradition involving local food products, en- the breakdown of traditional order as well as that vironment, climate, lifestyle, religion and related of traditional food culture. The traditional Japa- events. An established food culture influences di- nese dietary habits have been strongly influenced etary habits and behaviors, as well as consump- by global food cultures. As a result, fast foods tion of food materials, throughout the region and such as hamburgers, fried chicken, fried potato country. It has been thought that food cultures chips, pizzas, etc., have been displacing quite a could be preserved firmly; however, an observable large proportion of people’s diet, resulting in rap- change in dietary habits and patterns has occurred id disappearance of the traditional dietary habits, g 70 (63) (62) (67) (61) (62) (66) (65) 60 56.9 56.9 57.4 55.2 55.6 54.4 (67) 54.1 50 (61) 59.9 (63) (65) 46.5 55.3 54.0 Total intake including meat, poultry, (45) 40 fish, legumes, grains, eggs, nuts, etc. 36.0 30 (16) (29) 21.3 21.8 23.0 21.6 21.4 18.3 20.3 24.7 17.6 Fig. 1. Trends in fat intake in Japan 20 14.7 20.9 22.0 24.0 21.3 21.1 (per capita/day in parentheses and 11.1 10 5.6 national average). Since the 1980s, 2.8 Origin of meat & poultry except for fish and shellfish the leading lipid source has changed 0 from seafood and soybeans to meat, 1946 1950 1955 19601965 19701975 1980 1985 19901995 2000 2001 2002 2003 2004 concomitant with an increase in lip- Year id energy intake.

% 14 % Boys 6 12 4.97 5.1 Girls 5 10 2 4 8 3.19 3 6 1.89 2 4 1 2 0 0 1982–1986 1987–1991 1992–1996 1997–2001 1968 1977 1984 1988 1992 1996 2000 2004 Year Year

Fig. 2. The prevalence (%) of overweight and obesity has Fig. 3. The incidence rates (per 100,000) of type-2 diabe- doubled in children (12 years) over the last few de- tes in schoolchildren in a region of Japan (Kanagawa Pre- cades. fecture) [7].

particularly among children and adolescents. In gy intake decreased from 72.1 to 57.5% [3] . In other words, the clash of cultures has created var- 2004, the lipid intake exceeded 30% of total en- ious problems globally. ergy in young adults, 35% in children, and in adolescents it was about 25% [4] . A noteworthy finding regarding lipid sources is that in 1965 the Change in Dietary Habits and the leading sources were soybean and its related Consequences for Health products and seafood, but in 2004 it was meat [3] ( fig. 1). Thus, saturated fatty acids and n-6 long- In Japan, the lipid energy content in people’s diet chain polyunsaturated fatty acid (PUFA) intake has increased steeply in the last few decades. The has increased and, in contrast, unsaturated fatty lipid energy intake increased from 14.8% in 1965 acid and n-3 long-chain PUFA intake has de- to 26.5% in 2000, but carbohydrate (grain) ener- creased [3] . At the same time, the consumption of

Food Choices, Cultural Influences and Nutrition Transition 123 high energy-dense foods and sugared drinks has I n t e r v e n t i o n increased, while vegetable consumption has decreased [3] . In regions and countries such as Asia and the Mediterranean, people should reevaluate the advantages of their traditional diets, particularly Meal Patterns and Possible Consequences foodstuffs, over fast food, and these traditional diets can be modified to make them acceptable to Meal patterns tend to be changing from the for- young people. Perhaps, applying a similar idea to mer norm of three home-cooked meals a day, eat- other parts of the world can be recommended. en at fixed times with the family, to a new pattern Providing health education for both parents and among Japanese schoolchildren of eating out, go- children regarding healthy eating behaviors should ing without breakfast, and eating alone [4] . Con- be given high priority. Care messages from practi- currently, the prevalence of obesity and metabol- tioners can help make this change more effective. ic syndrome, such as type-2 diabetes, has increased [5] . Among Japanese schoolchildren, the rates of overweight and obesity were approxi- Conclusions mately 4 and 10% in 1968 and 2004, respectively [4] ( fig. 2 ). Regarding incidence of type-2 diabe- Globally, the clash of cultures has created various tes, it was 1.7 cases per 100,000 elder schoolchil- nutritional and health problems. One of the con- dren prior to the 1980s, and by 2000, depending cerns is the increased consumption of energy- on geographic location, the range of new cases dense foods with high contents of saturated fatty had risen to 5–8 children per 100,000 [6, 7] (fig. 3). acids and n-6 PUFA, associated with a high prev- This increasing trend is similar to that in other alence of obesity, type-2 diabetes even in children Asian countries, such as China [8] , Thailand [9] , and adolescents, and other health risks. Thus, bet- and Singapore [10] . ter health education is needed for both parents Although a traditional Asian-type diet should and children with a particular emphasis on healthy provide an advantage in preventing obesity and eating behavior, healthy meals and physical activ- its harmful consequences, global food culture ity. The avoidance of fast foods and replacing has obviously predominated over the traditional them with foods of high n-3 PUFA contents and dietary habits, after a period of clashing with it. green and yellow vegetables should be promoted.

References

1 WHO: The World Health Report 2005. 5 Sone H, Ito H, Ohashi Y, et al: Obesity 9 Likitmaskul S, Kiattisathavee P, Chai- Geneva, WHO, 2005. and type 2 diabetes in Japanese pa- chanwatanakul K, et al: Increasing

2 Yamori Y: Nutrition and ageing – im- tients. Lancet 2003; 361: 85. prevalence of type 2 diabetes mellitus portance of nutrition in Japanese lon- 6 Japanese School Health Report. Tokyo, in Thai children and adolescents asso-

gevity. APJCN 2002; 11(suppl 25). Japanese Ministry of Education, Cul- ciated with increasing prevalence of 3 National Health and Nutrition Survey ture, Sports, Sciences and Technology, obesity. J Pediatr Endocrinol Metab

in Japan. Tokyo, Japanese Ministry of 2005. 2003; 16: 71–77. Health, Labor and Welfare, 2006. 7 Yokota Y, Kikuchi N, Matsuura N: 10 Pan CY, So WY, Khalid BA, et al: Meta- 4 Japan Child and Family Research Insti- Screening for diabetes by urine glucose bolic, immunological and clinical char- tute: Almanac of Data on Japanese testing at school in Japan. Pediatr Dia- acteristics in newly diagnosed Asian

Children. Tokyo, KTC chuo, 2006. betes 2004; 5: 212–218. diabetes patients aged 12–40 years.

8 Liu JM, Ye R, Li S, et al: Prevalence of Diabet Med 2004; 21: 1007–1013. overweight/obesity in Chinese chil-

dren. Arch Med Res 2007; 38: 882–886.

124 Pediatric Nutrition in Practice Koletzko B. (ed): Pediatric Nutrition in Practice. Basel, Karger, 2008, pp 125–129

2 Nutrition of Healthy Infants, Children and Adolescents

2.10 Nutrition in Pregnancy and Lactation Renate L. Bergmann ؒ Karl E. Bergmann

Body Mass Index Key Words Pregnancy ؒ Lactation ؒ Weight gain ؒ Nutrient requirements, during pregnancy, lactation ؒ Body mass index (BMI) before pregnancy is a Supplements simple and useful indicator of nutritional status in clinical practice. Optimally, height without shoes and weight should be measured before Key Messages pregnancy [2] . R Weight gain during gestation is a determinant and an indicator of fetal growth 2 R Energy requirements during pregnancy are in- Gestational Weight Gain creased, but highly variable and adaptive R Monitoring weight gain provides an indicator of energy intake Gestational weight gain reflects fetal growth. A R Supplements of folic acid, iodine and iron should low weight gain is a risk indicator for intrauterine begin before pregnancy. Other critical micronutri- growth restriction and perinatal mortality, ents may be supplemented during pregnancy whereas a higher gain is a risk indicator for ma- R Pregnant women should not consume alcohol and ternal diabetes, macrosomia, delivery problems, illicit drugs, refrain from smoking and limit caffeine intake Copyright © 2008 S. Karger AG, Basel birth trauma and asphyxia. Intrauterine growth restriction as well as macrosomia may program obesity and the metabolic syndrome in later life [1, 2] . Total weight gain ranges for pregnant women with the best pregnancy outcomes for both Introduction mother and infant are classified according to prepregnancy BMI (table 1; fig. 1) [2, 3]. In full-term The nutritional status of women before and dur- twin pregnancies a total weight gain of 16–20.5 ing pregnancy is an important resource for the kg is associated with a favorable outcome. fetal and infant supply of nutrients. It is replen- ished and modified by nutrition before and during pregnancy and lactation. Maternal nutrition Weight Loss after Delivery not only influences the health and wellbeing of the mother but also has immediate and long-term Weight loss after delivery is higher in lactating effects on the development and health of the in- compared to non-lactating mothers. One year af- fant [1] . ter delivery, prepregnancy weight should again be reached. The mean weight gain of women is about 1 kg with each child. 18 BMI <19.8 16 BMI 19.8–26.0 14 BMI 26.0–29.0 12 10 8 6

Weight gain, kg 4 2 0 0 4 8 12 16 20 24 28 32 36 40 44 Fig. 1. Recommended mean weight Week of gestation gain for pregnant women by prepregnancy BMI [2, 15] .

Table 1. Recommended total weight gain ranges for Dietary restrictions during pregnancy and pregnant women by prepregnancy body mass index lactation should be avoided. Monitoring weight (BMI) [2] gain provides an indicator of adequacy of energy Weight-for-height category Recommended intake. total gain, kg

Low (BMI <19.8) 12.5–18 P r o t e i n I n t a k e s Normal (BMI 19.8–26.0) 11.5–16 High (BMI 26.0–29.0) 7–11.5 Protein intakes to meet the average requirement The recommended target weight gain for obese of 50% of women are estimated as: women (BMI >29.0) is at least 6.8 kg. • 0.88 g/kg/day in pregnancy • 1.05 g/kg/day during lactation [7] Recommended dietary allowances (meeting the requirements of 97–98% women) average: Energy Requirements • 1.1 g/kg/day in pregnancy • 1.3 g/kg/day during lactation [7] Energy requirements during pregnancy are high- While a high protein supply in pregnancy may ly variable. Energy-sparing adaptations can pro- be harmful [8] , a balanced energy/protein supple- tect the mother and fetus from nutritional strains ment (protein !25% of energy) influenced preg- [4] . The additional energy cost of pregnancy av- nancy outcome favorably [8] . erages 77,000 kcal [5] . For healthy women in the USA with a favorable pregnancy outcome and a normal BMI, the approximate energy needs com- Physical Aerobic Exercise pared to prepregnancy were [5, 6] : • ! 100 kcal/day in the first trimester Physical aerobic exercise (swimming, cycling, • 300 kcal/day in the second trimester floor exercise programs) at least two or three • 500 kcal/day in the third trimester times per week improves or maintains the physi- • 500–600 kcal/day during lactation [5] cal fitness of pregnant women [9] . A very high

126 Pediatric Nutrition in Practice physical activity level and a high workload may Table 2. Dietary reference intakes (DRIs) of selected nu- constrain fetal growth, and under unfavorable trients in pregnancy and lactation: recommended dietary allowances (RDA) and adequate intakes (AI) environmental conditions may lead to pregnancy loss. A lower risk of abnormal glucose tolerance Nutrient Pregnancy Lactation was observed in normal pregnant women who exercised during pregnancy [10] . Breastfeeding Vitamin A, ␮g/day 770 (10%) 1,300 (85%) success is not influenced by exercise or physical Vitamin C, mg/day 85 (13%) 120 (60%) Vitamin D, ␮g/day 5 (0%) 5 (0%) activity. Vitamin K, ␮g/day 90 (0%) 90 (0%) Folate, ␮g/day 600 (50%) 500 (25%) Vitamin B12, ␮g/day 2.6 (8%) 2.8 (17%) Recommended Dietary Allowances Calcium, mg/day 1,000 (0%) 1,000 (0%) Iodine, ␮g/day 220 (47%) 290 (93%) Iron, mg/dl 27 (50%) 9 (–50%)1 Recommended dietary allowances, i.e. the intake Magnesium, mg/day 350 (12%) 310 (0%) levels sufficient to meet the requirements of near- Phosphorus, mg/day 700 (0%) 700 (0%) ly all healthy pregnant and lactating women, or Zinc, mg/day 11 (38%) 12 (33%) adequate intakes are listed in table 2 [7] . Even in Total water, liters/day 3.0 (11%) 3.8 (41%) affluent populations, habitual intakes of some The additional intake (%) compared to non-pregnant critical nutrients may be marginal or deficient and non-lactating women of the same age group is (‘hidden hunger’) [11] . given in parentheses. 2 Folic Acid. An adequate and early supply of the Data from the Food and Nutrition Board, Institute of Medicine, National Academies, USA. B vitamin folic acid during the first 8 weeks of 1 Depends on blood loss at delivery. pregnancy has a strong protective effect against neural tube defects (NTD; spina bifida, anen- cephaly) [12] . Folate fortification programs of grain products have been introduced in about 40 countries worldwide and have been shown to ciency even a single high dose supplement (60,000 markedly reduce NTD incidence. Women of ␮ g) can be safely given to breastfeeding women childbearing age who may become pregnant and in the first 2 months after delivery. It has been women during at least the first 2 months of preg- estimated that about a quarter of the vitamin A nancy should aim to reach an added intake of requirement may be covered by ␤ -carotene which 400 ␮g/day of folic acid from supplements, forti- is not teratogenic. fied foods, or the combination of both. To pre- Iodine is needed for the synthesis of thyroid vent the recurrence of NTD in a subsequent preg- hormones. The most extreme manifestation of nancy, the folic acid supply should be maintained iodine deficiency in pregnancy is cretinism, but at 400 ␮ g/day, or if previously discontinued more subtle alterations in growth and devel- 4 mg/day should be taken [7] . opmental impairment are often overlooked. Vitamin A is required for normal embryonic Salt iodization has been implemented in many development. In populations with a high preva- countries to prevent iodine deficiency, but lence of vitamin A deficiency, supplements are iodine monitoring continues to indicate sub- desirable, while in developed countries routine optimal supplies. A supplement containing supplementation is not recommended. High dos- 100 ␮g/day iodine is recommended in Europe es (1 3,000 ␮ g/day preformed vitamin A) in early before and during pregnancy, and during lacta- pregnancy may be teratogenic and should be tion. avoided. But in populations with vitamin A defi-

Nutrition in Pregnancy and Lactation 127 Iron deficiency in pregnancy increases the risk creases the risk of abortions, preeclampsia and of maternal morbidity and mortality, premature preterm delivery. birth, low birthweight and stillbirth. Many wom- Vitamin B6 and Riboflavin. The vitamin B6 en start pregnancy with low iron stores. Infants and riboflavin status of pregnant and lactating of iron-depleted mothers have lower iron re- mothers is also critically reduced in many poor serves, may develop iron deficiency earlier, and areas of the world. may have delayed mental and psychomotor de- Fat-Soluble Vitamins and Docosahexaenoic velopment. The increased iron requirement dur- Acid. The concentrations of B vitamins, fat-solu- ing pregnancy usually cannot be covered by diet ble vitamins (A, D, E, K), and the long-chain alone. Low dose iron supplements (20–40 mg/ polyunsaturated fatty acid docosahexaenoic acid day) should optimally start before pregnancy. in breast milk are dependent on maternal stores Breast milk iron levels are low and not increased [11] . Women should have a regular dietary supply by iron supplements after delivery, which rather of these nutrients already in pregnancy, which serve to replenish maternal stores. continues in lactation (e.g. at least 200 mg/day of Zinc deficiency is common in developing coun- docosahexaenoic acid) [14] . tries, especially with parasitic infections. Zinc de- Screening of all pregnant women for the risk of ficiency may cause malformations, growth retar- micronutrient deficiencies and provision of indi- dation, and increased infant mortality. Zinc sup- vidually tailored advice is time-consuming and plements during pregnancy are vital in populations costly, indicators of micronutrient status in preg- at risk. nancy are not easy to interpret, and some inter- Calcium. The calcium transfer from the moth- ventions may come too late to affect outcome, er to the fetus is facilitated by calcium-regulating e.g. folic acid supplementation should start before hormones, while the calcium levels in maternal conception for optimal prevention of neural tube serum and bone are protected. Calcium loss from defects. bone occurs in breastfeeding mothers, regardless Information and Education at the population of dietary intake, and is reversed after weaning. level may achieve some effects and should be im- Dairy products are good calcium sources. Alter- plemented starting from school age, but food for- natively, calcium supplements may be taken dur- tification programs are more effective in achieving pregnancy and lactation. ing enhanced nutrient supplies on a population Vitamin D is required for absorption and uti- level. Most women who plan to become pregnant lization of calcium. Low serum 25-OH vitamin D or are pregnant will benefit from supplements levels are common in temperate climates, espe- containing multiple micronutrients at adequate cially in winter and spring, but occur also in geo- dosages. graphic locations with more sunshine where con- ventions do not allow sun exposure. Low fetal vitamin D stores can have long-term consequences C o n c l u s i o n s for bone mineral content. In countries without vitamin D fortification of dairy products, pregnant • Weight gain should be monitored longitudi- women should receive vitamin D supplements at nally on a graph according to prepregnancy least during the winter, e.g. 5 ␮ g/day [13] . BMI, and energy intake should be adapted to Vitamin B 12 . A low vitamin B12 status is preva- achieve adequate pregnancy weight gain [15] lent not only in strict vegetarians, but also in lac- • Women should eat a healthy mixed diet (food to-ovo-vegetarians, and even in those with ha- pyramid, food circle). Weight-losing diets bitually low meat consumption. A low supply in- should not be applied during pregnancy

128 Pediatric Nutrition in Practice • Pregnant women should drink plenty of wa- • Pregnant and lactating women should not ter consume alcohol and illicit drugs, should not • Aerobic, but not exhausting exercise is recom- smoke, and limit caffeine intake mended during pregnancy and lactation • Pregnant women should not consume raw or • Pregnant women should be supplemented undercooked eggs and unpasteurized milk with folic acid, iodine, iron, and potentially products. Meat and poultry should be thor- also with other critical micronutrients, de- oughly cooked, and fruits and vegetables pending on individual or regional risk, in ad- should be washed before consumption equate dosages • Pregnant and lactating women should have a regular dietary supply of docosahexaenoic acid (on average at least 200 mg/day), which can be achieved by 1–2 meals of ocean fish per week, including fatty fish, or by use of enriched foods/supplements

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2 Institute of Medicine: Nutrition during 79: 1078–1087. Rev 2001; 3:CD001056. DOI: Pregnancy. Washington, National 7 Otten JJ, Pitzi Hellwig J, Meyers LD 10.1002/14651858. Academy Press, 1990. (eds): Dietary Reference Intakes (DRI). 13 Hollis BW, Wagner CL: Assessment of 3 Abrams B, Altman SL, Pickett KE: Washington, Institute of Medicine, dietary vitamin D requirements during Pregnancy weight gain: still controver- National Academies Press, 2006. pregnancy and lactation. Am J Clin

sial. Am J Clin Nutr 2000; 71:S1233– 8 Kramer MS, Kakuma R: Energy and Nutr 2004; 79: 717–726. S1241. protein intake in pregnancy . Cochrane 14 Koletzko B, Cetin I, Brenna JT; Perina-

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and long-term consequences. Am J Clin 9 Kramer MS, McDonald SW: Aerobic tating women. Br J Nutr 2007; 98: Nutr 2000:S1226–S1232. exercise for women during pregnancy. 873–877.

5 FAO, Food and Nutrition Technical Cochrane Database Syst Rev 2006; 3: 15 Ochsenbein-Kölble N, Roos M, Gasser Report Series 1: Human Energy CD000180. DOI: 10.1002/14651858. T, Zimmermann R: Cross-sectional Requirements. Report of a joint FAO/ 10 Oken E, Ning Y, Rifas-Shiman S, et al: study of weight gain and increase in WHO/UNU Expert Consultation 2001. Associations of physical activity and BMI throughout pregnancy. Eur J

Rome FAO, 2004, pp 53–64. www.fao. inactivity before and during pregnancy Obstet Gynecol 2007; 130: 180–186. org/docrep/007/y5686e/y5686e00.htm. with glucose tolerance. Obstet Gynecol

2006; 108: 1200–1207. 11 Allen LH: Multiple micronutrients in pregnancy and lactation: an overview.

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Nutrition in Pregnancy and Lactation 129 Koletzko B. (ed): Pediatric Nutrition in Practice. Basel, Karger, 2008, pp 130–132

2 Nutrition of Healthy Infants, Children and Adolescents

2.11 Vegetarian Diets Jules Tolboom

Key Words of daily routine. Followers of macrobiotics, tran- -Vegetarian diet ؒ Dietary advice ؒ scendental meditation and anthroposophy all ad -Lacto-ovo-vegetarians ؒ Vegans ؒ Vitamin B 12 here to some form of a vegetarian diet. Environ mental awareness about the negative ecological impact of meat and poultry production may lead Key Messages to total abstinence from these products, while R Health consequences of vegetarian diets depend others only want to consume meat from ‘free on the dietary pattern followed range’ animals [1, 2] . Fear to contract bovine R A vegetarian diet can be a viable alternative to an spongiform encephalopathy motivates avoidance omnivoric diet if well devised of bovine meat products [3] . Approximately 2.5% R Children are at greater risk of nutritional deficiencies if very restricted vegetarian diets are fol- of adults in the United States and 4% of adults in lowed Canada follow vegetarian diets [4] . The wide R Macrobiotics and vegans are particularly at risk of spectrum of vegetarian diets ranges from avoid- vitamin B12 and iron deficiency and suboptimal ance of red meat only (‘semi-vegetarianism’) to growth that of all animal foods (‘vegans’). Halfway R Dietary assessment and growth monitoring is indicated for children on macrobiotic or vegan diets, through the spectrum are ‘lacto-vegetarians’ and while monitoring of hemoglobin and red cell indi- ‘lacto-ovo-vegetarians’, who also consume diary ces may be prudent products or dairy products and eggs, respec- Copyright © 2008 S. Karger AG, Basel tively. Clearly, the health consequences of vegetarian diets vary, depending on the dietary pattern followed. Children are at greater risk of nutritional Introduction deficiencies if very restricted vegetarian diets are followed. When joined with other dietary restric- When the word vegetarian (from ‘vegetus’, mean- tions such as avoidance of vitamin and mineral ing ‘lively’ or ‘vigorous’) was minted, halfway the supplements, objecting to food fortification or 19th century, it included a diet with eggs and only consumption of ‘organic’ foods, growth and milk [1] . health risks are likely to increase. The long-term Vegetarianism is strongly linked to sociocul- health benefits of vegetarian diets include re- tural traditions and religious, philosophical be- duced prevalences of hypertension, type-2 diabe- liefs. In Buddhism and Hinduism it is practiced tes, and reduced mortality from ischemic heart by some and for Seventh-Day Adventists it is part disease [4, 5] . Vegetarian diets for children need to support B12 content of the breast milk. These infants start normal growth, development and health, and to life with low stores of vitamin B 12 and are at risk cover dietary reference intakes. Overall, nutri- of developing vitamin B12 deficiency already ear- tional needs can be covered, but within a narrow- ly in childhood, which may result in permanent er margin than with a non-vegetarian (omnivor- neurological damage before megaloblastic ane- ic) diet [2, 3] . Dieticians and food scientists con- mia develops [8] . Vitamin B 12 supplementation or sider vegetarian diets a viable alternative to an food fortification is indicated for all infants, chil- omnivoric diet if well devised [4, 5] . Vegetarian dren, adolescents and adults on a vegan or mac- diets can even offer a number of nutritional ben- robiotic diet [4, 6, 7] . efits, including lower levels of saturated fat, cho- Vitamin D supplementation for fully breastfed lesterol, and animal protein as well as higher lev- infants of vegetarian mothers is only needed in els of carbohydrates, fiber, magnesium, potassi- case of limited exposure to sunlight, similar to um, foliate, and antioxidants such as vitamins C infants of non-vegetarian mothers. Lacto- and and E and phytochemicals [4] . Infants and chil- lacto-ovo-vegetarian children consume suffi- dren on very restricted vegetarian diets, like mac- cient vitamin D-fortified cow’s milk [3] . Vitamin robiotic diets, are at increased risk of nutrient D supplementation is needed for all vegan chil- deficiency and insufficient growth [4, 6, 7] . Ex- dren with inadequate exposure to sunlight. clusive breastfeeding by vegetarian mothers con- Calcium intake of lacto- and lacto-ovo-vege- suming well-balanced diets is sufficient for nor- tarian children is usually adequate [9]. This is 2 mal growth and development during the first 6 generally not the case in children on vegan or months of life. Problems arise when the vegetar- macrobiotic diets. For those, very high intakes of ian diet of the mother during pregnancy and lac- calcium, rich green leafy vegetables and nuts will tation and that for the child during the weaning be needed. More effective is the use of calcium- period and thereafter is very restricted [3, 4] . If no fortified foods like soy products [3, 4]. Since in- food of animal origin is consumed at all, as is the testinal calcium absorption is dependent on vita- case for all vegans, the risk of specific nutrient min D, an adequate vitamin D intake may partly deficiencies increases markedly. offset a low calcium content of the diet [3] . Iron deficiency is by far the most common micronutrient deficiency in children, more so in Risk of Nutrient Deficiency vegetarian and especially in vegan children, since the latter do not consume any heme iron from This applies to all nutrients that are: (1) exclu- meat, poultry or fish [2, 3]. Iron availability from sively found in foods of animal origin; (2) only in plant sources is much lower because of the pres- relative small quantities present in the vegan diet, ence of fiber, phytates, tannins and other poly- and (3) poorly absorbed in the gut because of a phenols [2, 10, 11] . Iron absorption is enhanced high oxalate or phytate content of the vegetarian by the presence of organic acids like ascorbic and diet. Health risks further increase if the practice citric acid. The risk of iron deficiency can be less- of avoiding all animal products is coupled with ened by using plant food with a high iron content an unwillingness to seek professional dietary ad- or iron-fortified food products, e.g. breakfast ce- vice and to accept supplementation or food forti- real [1–4] . fication. Zinc deficiency is one of the least known dan- Vitamin B 12 supplementation is already need- gers of vegetarian diets [2] . Food from animal ed for all infants of marginally vitamin B12 -defi- sources contains zinc but does not contain zinc cient vegan mothers because of the low vitamin absorption-inhibiting factors such as phytate and

Vegetarian Diets 131 oxalate compounds that are found in plant food • Vitamin B 12 supplementation or food fortifi- [10, 11] . Like iron, zinc is amply present and bio- cation is indicated for all infants, children, ad- available in red meat. Human milk contains zinc olescents and adults on a vegan or macrobi- in bioavailable form, but children older than 7 otic diet months need some form of zinc supplement or • Vitamin D supplementation is needed for all fortified food [3] . Macrobiotics and vegans have vegan or macrobiotic children with inade- a higher risk of zinc deficiency [2] . quate exposure to sunlight • Calcium intake of children on vegan or macrobiotic diets may be too low Conclusions • Iron deficiency is more likely to occur in macrobiotic and vegan children • A prerequisite for optimal growth, develop- • Zinc deficiency is one of the least known dan- ment and health is a vegetarian diet that has a gers of vegetarian diets sound dietetic basis and covers dietary reference intakes

References

1 Whorton JC: Vegetarianism; in Kipli 5 American Dietetic Association; Dieti- 8 Herbert V: Vitamin B12 : plant sources. KF, Ornelas KC (eds): The Cambridge cians of Canada: Position of the Ameri- Requirements and assay. Am J Clin

World History of Food. Cambridge, can Dietetic Association and Dieticians Nutr 1998; 48(suppl):S852–S858. Cambridge University Press, 2000, pp of Canada: vegetarian diets. J Am Diet 9 Tayter MS, Stanek KL: Anthropometric

1553–1564. Assoc 2003; 103: 748–765. and dietary assessment of omnivore 2 Abrams HL: Vegetarianism: another 6 Dagnelie PC, van Staveren WA, Ver- and lacto-ovo vegetarian children. J

view; in Kipli KF, Ornelas KC (eds): The schuren SA, Hautvast JG: Nutritional Am Diet Assoc 1989; 89(suppl):1661– Cambridge World History of Food. status of infants on macrobiotic diets 1663. Cambridge, Cambridge University aged 4 to 18 months and matched om- 10 Harland BF, Orberleas D: Phytate in

Press, 2000, pp 1564–1573. nivorous control infants: a population- foods. World Rev Nutr Diet 1987; 52: 3 Kleinman RE (ed): Nutritional Aspects based mixed-longitudinal study, I: 235–259. of Vegetarian Diets. Pediatric Nutrition weaning pattern, energy, and nutrient 11 Hunt JR: Bioavailability of iron, zinc,

Handbook, ed 5. Elk Grove Village, intake. Eur J Clin Nutr 1989; 43: 311– and other trace minerals from vegetar-

American Academy of Pediatrics, 2004, 323. ian diets. Am J Clin Nutr 2003; 78 pp 191–208. 7 Dagnelie PC, van Staveren WA: Macro- (suppl):S633–S639. 4 Key TJ, Davey GK, Appleby PN: Health biotic nutrition and child health: benefits of vegetarian diet. Proc Nutr results of a population-based mixed-

Soc 1999; 58: 271–275. longitudinal cohort in The Nether-

lands. Am J Clin Nutr 1994; 59(suppl): S1187–S1196.

132 Pediatric Nutrition in Practice Koletzko B. (ed): Pediatric Nutrition in Practice. Basel, Karger, 2008, pp 133–136

3 Nutritional Challenges in Special Conditions and Diseases

3.1 Primary and Secondary Undernutrition Kraisid Tontisirin ؒ Lalita Bhattacharjee

Key Words children. Alongside the devastating effects on Undernutrition ؒ Infection ؒ Feeding, infant and health and wellbeing due to undernutrition in young child ؒ Community ؒ Integrated approach developing countries, the rapid changes in diet and lifestyle – ‘nutrition transition’ – have resulted in escalating numbers of overweight and obese Key Messages individuals with increased risks of chronic non- R Undernutrition poses serious threats to children’s communicable diseases such as hypertension, health heart disease and diabetes. The double burden of R Undernutrition exists in both poor and affluent malnutrition, as it is called, is found to coexist societies within communities and even within households R Maternal, infant and young child feeding are important components of the essential care pack- [3, 4]. For the purpose of this chapter, undernutri- age tion refers to any physical condition implying ill 3 R Family and community orientation services should health or the inability to maintain adequate be provided at health centers growth, appropriate body weight and body com- R Facilitating the delivery of health services at sub- position, or to sustain acceptable levels of eco- national levels and empowering the family and community are sustainable approaches to prevent nomically necessary and socially desirable physi- and control undernutrition cal activities brought about by an inadequacy in Copyright © 2008 S. Karger AG, Basel food, both in quantity and in quality. This chapter provides an understanding of primary and secondary undernutrition in that it must be viewed not only as a major factor in the causation Introduction of disease but also in exacerbating the disease situation which poses threats to children’s health. It Nutrition plays a vital role in maintaining good suggests a strategic community-based approach health, and undernutrition generates vulnerabil- towards addressing primary and secondary un- ity to a wide range of diseases and general ill dernutrition, and provides practical examples of health [1, 2] . Undernutrition diminishes the abil- food-based nutrition actions for implementation ity of all systems of the body to perform properly, in the developing world. with particular grave consequences in young Definitions and Need to Assess the Extent of communicable and vaccine-preventable diseases. the Problem Although the reported coverage rates for most vaccines included in the WHO’s expanded pro- Primary undernutrition is the outcome of insuf- gram on immunization range from 67 to 99% in ficient food caused primarily by an inadequate southeast Asian countries, in reality vaccination intake of dietary or food energy whether or not coverage rates are much lower [7] . any specific nutrient deficiency is present. Un- dernutrition is also defined as a dietary energy intake below the minimum requirement level to Maternal Undernutrition maintain the balance between energy intake and energy expenditure. Primary undernutrition, Maternal undernutrition, both acute and chron- also referred to as protein-energy malnutrition ic, in the prepregnant and pregnant state is close- (PEM), increases vulnerability to infectious dis- ly implicated in the etiology of PEM. Maternal eases since energy, protein, and certain vitamins undernutrition, which is often manifested as and minerals play crucial roles in immune func- chronic energy deficiency, threatens health and tion. In environmental contexts in which infec- survival because it increases mother’s suscepti- tious diseases (especially diarrheal disease and bility to life-threatening diseases and increases respiratory tract infections) are common, the their risk of dying during child birth. Maternal combination of PEM and infection can provoke a mortality rates in developing countries such as rapid deterioration of health that can even lead to south Asia are among the highest in the world death. Secondary undernutrition is due to sec- [8] . Most mothers with chronic energy deficiency ondary causes that limit an adequate supply of are likely to give birth to low birthweight babies nutrients to the body. These include disorders (! 2.5 kg). that affect gastrointestinal function, wasting disorders and conditions that increase metabolic demands such as infections, hyperthyroidism, oth- Infant and Young Child Feeding er endocrine disorders, burns, trauma, surgery, and other critical illnesses and conditions. The The importance of breast milk as the best and causes of primary and secondary undernutrition only food for infants up to about 6 months of age are multidimensional and synergistic, with inad- is universally recognized. At the policy level, the equate food availability being the primary, and promotion and protection of and support for uni- inadequate utilization of the food consumed the versal breastfeeding is reinforced by the Code of secondary factor [5] . Examples from Bangladesh Marketing of Breast-Milk Substitutes. From 6 and China show that even in food-secure or high- months, adequate complementary feeding should income households, some members may be un- be given, while breastfeeding is continued to dernourished while others may be overweight, maintain normal growth rates [9] . The composi- suggesting that both situations may be seen with- tion of the complementary food mix is therefore in the same household [6] . Outside the critical pe- critical as it must be adequate in energy, protein riod of childbirth, while undernutrition is a ma- and micronutrients and be given frequently jor cause of child death, a large proportion of enough to meet the nutrient needs of the infant. child deaths are also related to infectious diseas- Several countries have undertaken the develop- es. The WHO estimates that children under 5 ment of complementary feeding guidelines. Ta- years account for 90% of these deaths. A large ble 1 illustrates complementary feeding guide- proportion (60%) of these deaths are related to lines which could be integrated as part of an over-

134 Pediatric Nutrition in Practice all strategy to increase household food security Table 1. Suggested complementary feeding guidelines and nutrition [10] . The rationale for the selection (adapted from Thailand complementary feeding guidelines) of complementary foods is based on the knowledge of what is culturally acceptable, foods that 0–6 months Exclusive breastfeeding are locally available, and foods that can be made 6 months Begin with rice gruel, ripe banana; more readily available through promoting food add egg yolk, chicken liver or legumes, production at the community level. fish and dark green leafy vegetables or pumpkin or carrots 7 months Add ground meat including chicken, Family and Community Orientation whole egg, well-cooked soft fish (as appropriate), and other fruits like Family and community orientation services ripe papaya and mango, progressing slowly until the child takes one should be provided at health centers. Health pro- complete meal fessionals, particularly at sub-national levels (dis- 8–9 months Give 2 complete meals trict) should plan and work in collaboration with 10–12 months Give 3 complete meals the community to implement these services. As part of the planning process, the health services delivery personnel (at district/sub-national level) can act as facilitators in coordination with the Table 2. Systematic approach to integrate primary community leaders (village level). The health healthcare in the prevention and control of undernutri- professionals and the community leaders will tion need to set realistic goals collectively and develop workable plans for the prevention and control of First contact undernutrition (PEM). A comprehensive health History and physical examination Growth assessment services package integrating many elements of Assessment of the undernutrition problem health, nutrition, food production (in the case of Initiation of health and nutrition education subsistence farmer households and others), edu- Treatment/care plan 3 cation and community development should be Subsequent contact made available through the center to enable Growth monitoring and promotion activities mothers and communities to support their chil- Breastfeeding dren’s optimal nutrition [11] .Training of the com- Complementary feeding Health and nutrition education munity leaders and volunteers and support of Immunization district level leadership would need to be an on- Treatment of infection going part of the process [12] . Family and community orientation The fact that undernutrition is understood to Health professionals need to integrate health, nutrition have many causes should not inhibit practical and education modules and resources to prevent and and appropriate actions. Rather, this understand- control undernutrition ing should promote a better awareness of sectoral opportunities that need to be availed of to overcome undernutrition. Health professionals at all levels should use information derived from their who collect the data are best able to use it. This understanding more effectively in a timely man- will link progressively decentralized decision- ner. It should be used at the level where informa- making by health professionals and communi- tion is generated, particularly when the people ties. Health professionals would need to facilitate

Primary and Secondary Undernutrition 135 and provide the delivery of necessary and imme- • Programs should be designed to strengthen diate medical services to the child and family and the interface between service delivery and the also specifically serve to involve the individual community by creating a demand for the ser- and family through a process of empowerment in vices undernutrition prevention and control strategies • Community leaders, through the community [13, 14]. This is but a systematic approach to inte- infrastructure, will need to organize mecha- grate primary healthcare principles in the pre- nisms to identify and select community vol- vention and control of undernutrition ( table 2). unteers or ‘mobilizers’ who can actually provide the health services package at the community or household level Conclusions • A community-based approach can lead to improved outreach and coverage of services and • Prevention and control of undernutrition will lead to an improvement in child health must entail a comprehensive approach and and nutrition on a sustainable basis need to be undertaken by health and related professionals at individual and community levels

References

1 Semba RD, Bloem M (eds): Nutrition 6 Shafique S, Akhter N, Stallkamp G, et 11 Tontisirin K, Winichagoon P: Commu- and Health in Developing Countries. al: Trends of under- and overweight nity based programs: success factors Towota, Humana Press, 2001. among rural and urban poor women for public nutrition derived from the 2 Martorell R, Haschke F (eds): Nutrition indicate the double burden of malnutri- experience of Thailand. Food Nutr Bull

and Growth. Nestlé Nutr Workshop Ser tion in Bangladesh. Int J Epidemiol 1999; 20: 315–322.

Pediatr Program. Philadelphia, Lippin- 2007; 36: 449–457. 12 Tontisirin K, Gillespie S: Linking com- cott, Williams & Wilkins, 2001, vol 47. 7 WHO: World Health Report 2002 – munity based programs and service 3 Popkin BM: The nutrition transition Reducing Risks, Promoting Healthy delivery for improving maternal and

and obesity in the developing world. J Life. Geneva, WHO, 2002. child nutrition. Asian Dev Rev 1999; 17:

Nutr 2001; 131:S871–S873. 8 Bloem MW, Moench-Pfanner R, Pana- 33–65. 4 Popking MP: The nutrition transition gides D (eds): Health and Nutritional 13 Tontisirin K, Winichagoon P, Bhat- and its relationship in demographic Surveillance for Development. Singa- tacharjee L: Protein energy malnutri- change; in Semba RD, Bloem MW (eds): pore, Helen Keller Worldwide, 2003. tion, prevention and control: effective Nutrition and Health in Developing 9 WHO: Protecting, Promoting and Sup- approaches for use by health profes-

Countries. Towota, Humana Press, porting Breast-Feeding: the Special sionals. Ann Nestlé 1999; 57: 107–118. 2001. Role of Maternity Services. A joint 14 Khammounheuang K, Saleumsy P, Kir- 5 Shetty P: Measures of nutritional status WHO/UNICEF statement. Geneva, javainen L, et al: Sustainable liveli- from anthropometric survey data; in WHO, 1989. hoods for human security in Lao PDR: Methods for the Measurement of Food 10 Tontisirin K, Yamborisut U: Appropri- home gardens for food security, rural Deprivation and Undernutrition. Pro- ate weaning practices and foods to pre- livelihoods and nutritional well-being.

ceedings of an International Scientific vent protein-energy malnutrition: an Reg Dev Dialogue RDD 2004; 25: 203–

Symposium, 2002. Rome, FAO, 2003. Asian enigma. Food Nutr Bull 1995; 16: 228. 34–39.

136 Pediatric Nutrition in Practice Koletzko B. (ed): Pediatric Nutrition in Practice. Basel, Karger, 2008, pp 137–141

3 Nutritional Challenges in Special Conditions and Diseases

3.2 Iron Deficiency and Other Nutrient Deficiencies Noel W. Solomons

Key Words trient-rich food. The advent of the agricultural Micronutrient deficiencies ؒ Iron ؒ Anemia ؒ era placed reliance on nutrients primarily on a Eating disorders ؒ Chronic disease ؒ Iatrogeny narrow selection of grains and tubers, exposing humankind to the risk of vitamin and mineral deficiencies. Table 1 illustrates the various mech- Key Messages anisms that can contribute to nutrient deficien- R Iron deficiency and anemia are the most wide- cies [1] . spread human deficiencies and produce reduced productivity and learning R Endemic deficiencies of vitamin A and zinc are as- The Clinical Contexts of Micronutrient sociated with greater infectious morbidity in children Deficiencies R Eating disorders, clinical illness and iatrogenic causes are the bases of micronutrient deficiencies The various contexts within which micronutri- in clinical pediatrics ent deficiencies can occur are outlined in table 2 3 R The combination of addressing the underlying [2] . Among the vitamins, deficiencies of vitamins causes and providing prudent supplementation A, D, C, B , B , thiamin, riboflavin, niacin, and with vitamins and/or minerals is essential to re- 6 12 solving micronutrient malnutrition folic acid can be encountered in free-living chil- Copyright © 2008 S. Karger AG, Basel dren in a public health context as a result of social or environmental adversity or abuse. Similarly, nutritional deficiencies of phosphorus, magnesium, iron, zinc, iodine, fluorine and selenium Introduction can occur in sectors of a free-living public. In a public health sense, deficiencies of micronutri- Micronutrients (vitamins and minerals) are es- ents have recently been termed ‘hidden hunger’ sential for human health, growth, and develop- because the nutrients responsible for the defi- ment. Humans evolved as hunter-gatherers, ex- ciency cannot be seen in the foods, and one might pending large amounts of energy to obtain suste- be consuming sufficient total energy and macro- nance from wild plants and hunted game. The nutrients, and still suffer a vitamin or mineral evolutionary complementary feeding of infants deficit [3] . involved pre-masticated meat. As such, humans Clinical deficiencies of vitamins E and K, pan- evolved consuming large amounts of a micronu- tothenic acid and biotin among vitamins, and Table 1. Mechanisms contributing to micronutrient calcium, copper, selenium, molybdenum, chro- malnutrition mium and manganese among minerals, have Insufficient intake of nutrient in relation to been documented only with severe disorders in requirements pathophysiology or due to iatrogenic factors, or Impaired intestinal nutrient absorption in some cases, with controlled experimental de- Diminished whole-body retention of nutrient pletion in adult volunteers. The deficiencies of Impaired cellular nutrient utilization this group of nutrients do not represent a public Enhanced intrinsic destruction of nutrient health concern.

Specific Nutrient Deficiencies of Public Health Table 2. The scenarios and contexts for developing Importance, Afflicting Those Consuming Poor micronutrient malnutrition Diets and under Environmental Stress Adverse social or environmental conditions Poverty or displacement, which interfere with the A selected cluster of six micronutrients merit in- access to food; disruptions in agriculture or trade, depth mention and consideration as their pre- which interfere with the availability of food; unsanitary vention, mitigation, and therapy can represent a conditions or transmission of pathogens, which compromise the absorption or retention of nutrients public health challenge. Eating disorders or abuse Emotional disturbances related to food or intentional Iron Deficiency and Iron Deficiency Anemia restriction or deprivation of food by caretakers Iron is the most important and challenging of the public health micronutrient deficiencies. It is es- Clinical illnesses Disease states with pathophysiological effects that timated that from 2 to 5 billion of the world’s impair the consumption, absorption, utilization or 6 billion inhabitants are iron-deficient, and from retention of nutrients one third to one sixth of these have microcytic, Iatrogenic factors hypochromic anemia attributable to iron defi- Inappropriate withholding of essential nutrients or ciency. Iron deficiency has a series of functional prescription of medications with anti-nutritional effects consequences as outlined in table 3 . These are common to the condition, whether or not it is associated with anemia. Hence, iron deficiency disorders can take a devastating toll on the fitness of Table 3. Functional consequences of iron deficiency both individuals and the communities of which they are a part [4] . – Reduced cognitive development as measured by Among the risk factors for iron deficiency are: intelligence quotient – Reduced attention span reliance on iron-poor foods such as milk and – Poor learning and impaired scholastic performance dairy products (including human milk), rice, – Decreased exercise stamina fruits, and fleshy vegetables; reliance on foods of – Reduced muscular force and strength low iron bioavailability, and blood-feeding para- – Impaired body temperature regulation – Immune deficiencies involving macrophage and sites [5] . Iron deficiency is common in infants, in neutrophil phagocytosis, T-cell proliferation, and the second semester of infancy as well as in ado- interleukin-2 responses lescence, due to rapid growth in boys and to the – Depriving intracellular pathogens of the iron needed onset of menarche in girls. for proliferation and virulence and protecting the The mechanisms of host defense against in- host from more severe consequences of infection fection exclude iron from cells and sequester the

138 Pediatric Nutrition in Practice iron within cells into ferritin in an attempt to de- ting adequate zinc is especially challenging dur- prive pathogenic organisms of iron. For certain ing the period of weaning, as virtually no unfor- intracellular pathogens, iron deficiency of the tified complementary food can provide the rec- host may confer relative protection. ommended intakes for late infancy [9] . Zinc deficiency is associated with impaired Hypovitaminosis A immune function, and recent epidemiological The most heralded consequences of vitamin A studies indicate that child deaths from respira- deficiency are night blindness (failure to adapt to tory and gastrointestinal infections could be revision in dim light) and xerophthalmia (ocular duced by assuring adequate zinc nutrition in at- lesions that can lead to nutritional blindness). risk populations. However, the most devastating manifestation is for marginal vitamin A deficiency, which is as- V i t a m i n B 12 Deficiency sociated with an increased risk of mortality from Although it was thought to be a predominant con- common childhood infections and measles [6] . dition of the elderly, recent surveys in Africa and Worldwide, at any given time, less than 5 million MesoAmerica indicate high prevalences of low children have a certain stage of xerophthalmia, vitamin B12 status [10] . A combination of dietary whereas 130 million preschool children will have insufficiency with environmental factors impair- some degree of hypovitaminosis A. Risk factors ing gastric (Helicobacter pylori) and intestinal include a predominantly plant-based diet, severe (bacterial overgrowth) health contribute to this infections such as measles, AIDS and tuberculo- condition as a pediatric public health problem. sis, recurrent gastrointestinal or respiratory infections, and poor hygienic living conditions [7] . Hyporiboflavinosis In actual numbers, it is probable that more chil- Iodine Deficiency Disorders dren worldwide have a marginal riboflavin status Millennia of soil leaching has depleted most soils (as indicated by abnormal values on a biochemi- of iodine. During the 1990s, a major international cal biomarker of riboflavin status, erythrocyte public health effort raised the coverage of iodized glutathione reductase activity coefficient) than 3 salt from 20% to over 80%, improving iodine even iron deficiency. Severe riboflavin deficiency status worldwide. Yet, an estimated 285 million with clinical manifestations is rare, and most of- schoolchildren, worldwide, are at risk of suffering ten seen in the context of multiple micronutrient iodine deficiency disorders. In areas of the inte- deficits. rior of central Africa, where the myxedematous form of goiter exists, an environmental scarcity of selenium has been suggested as the factor which Micronutrient Deficiencies in Other Pediatric produces profound hypothyroidism [8] . Contexts

Zinc Deficiency Micronutrient Deficiencies in Eating Disorders Zinc is virtually absent in fruits, vegetables and Eating disturbances and disorders can contribute tubers, and the zinc content in legumes and whole to serious micronutrient deficiencies [11] . This grains is tightly bound by phytic acid, and not ranges from picky-eating and fear of fatness in easily available for intestinal absorption. It has younger children to overt anorexia nervosa and thus been postulated that zinc deficiency is wide- bulimia in adolescents. The addition of emetics spread and responsible for some of the linear and laxatives to control weight gain aggravates growth retardation in developing countries. Get- nutrient absorption and retention. Cases of in-

Iron Deficiency and Other Nutrient Deficiencies 139 Table 4. Selection of chronic diseases of childhood fre- The essential purpose of the alimentary tract quently associated with micronutrient deficiency states is to obtain nutrients; therefore any digestive or Systemic diseases absorptive disorders will compromise nutrient Severe chronic diseases uptake [12] . Virtually all vitamins and minerals (tuberculosis, HIV/AIDS, malaria) can be adversely affected by small bowel diseases. Rheumatoid arthritis Blood loss leading to iron deficiency is common Gastrointestinal diseases in inflammatory bowel disorders. Neuromuscu- Inflammatory bowel disease lar disorders interfere with proper chewing and (Crohn’s disease, ulcerative colitis) swallowing, often limiting the quantity and vari- Small bowel disease (short bowel syndrome, celiac disease) ety of dietary intake. Pancreatic insufficiency Diabetes mellitus is associated with deficien- (cystic fibrosis) cy of a number of minerals. Magnesium, calci- Hepatic disease um and phosphorus can be wasted in chronic (biliary atresia, post-hepatitic cirrhosis) renal disease, as well as all water-soluble vita- Neurological diseases mins; fat-soluble vitamin levels in the circula- Neuromuscular disorders tion are frequently elevated. Chronic hemo- and (cerebral palsy, muscular dystrophy) peritoneal dialysis generally progressively de- Endocrinological disease plete vitamins. Diabetes mellitus Acrodermatitis enteropathica and Menkes Renal disease disease represent examples of congenital illnesses Chronic renal disease (glomerulonephritis, extracorporeal dialysis) that affect the cellular transporters for zinc and copper, respectively. This results in total body de- Congenital disorders pletion of zinc and the manifestations of severe Acrodermatitis enteropathica Menkes disease zinc deficiency. The defect of copper transport in Menkes disease is not only in the gut but throughout the body, generating profound signs of copper depletion through impaired utilization of the metal. duced childhood micronutrient deficiencies have been recorded in children raised in cults with un- Iatrogenic Causes of Micronutrient Deficiencies orthodox vegetarian dietary practices. Prescriptions and practices of clinical practitioners can contribute iatrogenic causes of micronu- Chronic Clinical Disorders and Micronutrient trient deficiencies. Improper formulation of in- Deficiencies fant formula, enteral feedings and parenteral in- Table 4 summarizes selected clinical disorders fusions has produced deficiencies of vitamin E, contributing to micronutrient deficiency. A se- zinc, copper, selenium, molybdenum and chro- ries of nutrients that are wasted in the urine, in- mium, as well as chloride [13, 14] . A variant of cluding vitamin A and trace elements, will be lost this mechanism is the addition of a medication to in excess with systemic inflammatory responses, a formula that destroys or inactivates a nutrient. as seen in AIDS, tuberculosis, malaria and sys- Prolonged use of antibiotics, purging the intesti- temic parasitoses. Urinary nutrient wasting also nal flora, has contributed to vitamin K and biotin occurs in certain renal diseases in which the deficiency. Other medications interfere with the glomeruli become porous, tubular reabsorption absorption or utilization of one or another mi- is impaired, or both. cronutrient. Sulfasalazine, for example, interferes

140 Pediatric Nutrition in Practice with folate absorption and metabolism. Antacids • The practitioner must know the signs and and acid-blocking drugs create pH and secretory symptoms and appropriate interpretation of conditions in the stomach and upper intestine. hematological, biochemical and functional The roster of drug–nutrient interactions compro- indices of vitamin and mineral deficiencies mising micronutrient malnutrition is exhaustive, • The appropriate prescription of the deficient and cannot be covered in full here. nutrient, combined with attention to the underlying cause(s) of deficiency, should restore an adequate state of micronutrient nu- Conclusions trition

• Children commonly develop overt deficiencies of only certain vitamins (A, D, C, B 6 , B 12 , thiamin, riboflavin, niacin, folic acid) and minerals (phosphorus, magnesium, iron, zinc, iodine, fluorine and selenium)

References

1 Herbert V: The five possible causes of 6 Sommer A: Vitamin A deficiency and 10 Casterline JE, Allen LH, Ruel MT: Vita-

all nutrient deficiencies, as illustrated the global response. Forum Nutr 2003; min B-12 deficiency is very prevalent in

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late. Am J Clin Nutr 1973; 26: 77–88. 7 Solomons NW: Vitamin A; in Russell infants at three month postpartum. J

2 Solomons NW: Malnutrition (b) sec- RM, Bowman BA (eds): Present Knowl- Nutr 1997; 12: 1966–1972. ondary: diagnosis and management; in edge in Nutrition, ed 9. Washington, 11 Castro J, Deulofeu R, Gila A, et al: Per- Caballero B, Allen LH, Prentice A (eds): ILSI Press, 2006, pp 157–183. sistence of nutritional deficiencies after Encyclopedia of Human Nutrition, ed 8 Contempre B, de Escobar GM, Denef JF, short-term weight recovery in adoles- 2. London, Elsevier Science, 2005, vol et al: Thiocyanate induces cell necrosis cents with anorexia nervosa. Int J Eat

2, pp 212–216. and fibrosis in selenium- and iodine- Disord 2004; 35: 169–178. 3 3 Maberly GF, Trowbridge FL, Yip R, et deficient rat thyroids: a potential ex- 12 Cerda JJ, Artnak EJ: Nutritional aspects al: Program against micronutrient mal- perimental model for myxedematous of malabsorption syndromes. Compr

nutrition: ending hidden hunger. Annu endemic cretinism in central Africa. Ther 1983; 9: 35–46.

Rev Publ Health 1994; 15: 277–301. Endocrinology 2004; 145: 994–1002. 13 Agostoni C, Haschke F: Infant formu- 4 Beard J: Iron; in Bowman AB, Russell 9 Dewey KG, Brown KH: Update on tech- las. Recent developments and new is-

RM (eds): Present Knowledge in Nutri- nical issues concerning complementary sues. Minerva Pediatr 2003; 55: 181–194. tion, ed 9. Washington, ILSI Press, feeding of young children in develop- 14 Baumgarten T (ed): Clinical Guide to 2006, pp 445–457. ing countries and implications for in- Parenteral Micronutrition, ed 3. Chi- 5 Viteri FE, Warren R: Considerations tervention programs. Food Nutr Bull cago, Fujisawa-USA, 1997.

on the use of radioisotopes in human 2003; 24: 5–28. nutrition research. Food Nutr Bull

2002; 23(suppl 3):7–16.

Iron Deficiency and Other Nutrient Deficiencies 141 Koletzko B. (ed): Pediatric Nutrition in Practice. Basel, Karger, 2008, pp 142–146

3 Nutritional Challenges in Special Conditions and Diseases

3.3 Enteral Nutrition Support Sanja Kolaček

Key Words There are only a few absolute contraindica- -Enteral nutrition, provision and administration ؒ tions for EN such as necrotizing enterocolitis, in Tube feeding testinal perforation, gastrointestinal obstruction, and severe/septic intra-abdominal infection. When the clinical condition of the patient is Key Messages stable, home EN should be considered [2] . Al- R Enteral nutrition should be introduced in a patient though a dedicated team approach is required with preserved intestinal function but unable to whenever EN is provided [3] , it is particularly im- meet dietary requirements by an oral route portant to teach parents and children the tech- R Close monitoring and strict adherence to estab- niques required for EN before being discharged, lished protocols are important as different complications may occur such as nasogastric (NG) tube placement and R Enteral nutrition can be stopped when oral intake maintenance, sterile feed preparation and ad- satisfies nutritional requirements, and growth con- ministration, enteral pump management, and tinues to be age appropriate prevention, recognition and management of the Copyright © 2008 S. Karger AG, Basel most common complications. Transition to normal oral feeds needs to be gradual, and EN can be stopped when oral intake Introduction satisfies caloric and nutrient requirements, while growth continues to be age appropriate. Enteral nutrition (EN) is defined as oral feeding using special formulae, or tube feeding directly into stomach, duodenum or jejunum. In general, Enteral Formula Properties and Selection it should be introduced in a child who has a Criteria sufficient level of gastrointestinal function preserved, but is unable to meet energy and nutrient Enteral formulas differ in the source and content requirements by a normal oral diet. When com- of nutrients, caloric density, osmolality, and cost pared to parenteral feeding, EN has numerous [4] . At standard dilution, the energy content of advantages such as preservation of gastrointesti- infant formula is 0.67 kcal/ml and that of stan- nal function, lower costs, better manageability dard pediatric enteral feed is 1 kcal/ml. More and increased safety. EN should be considered concentrated enteral formulas are also available when one or more of the factors presented in ta- (1.3–2.0 kcal/ml) for patients with increased en- ble 1 are identified [1] . Various clinical indica- ergy requirements or limited fluid intake. With tions are listed in table 2 . regard to carbohydrates, maltodextrin and hy- Table 1. General indications for enteral feeding [1] Table 2. Clinical indications for pediatric enteral nutrition EN to be considered when one or more of the following is present: 1 Inadequate oral intake a Inadequate growth or weight gain for >1 month, – Disorders of sucking and swallowing: prematurity, under age of 2 years cheilognathopalatoschisis, neuromuscular b Weight loss/no weight gain for >3 months, over age impairment (e.g. cerebral palsy, myopathies, etc.) of 2 years – Congenital abnormalities of the upper c Change in weight/age or weight/height over 2 gastrointestinal tract: tracheoesophageal fistula growth channels – Tumors of oral cavity, head and neck cancer d Triceps skinfolds consistently <5th percentile for age – Trauma and extensive facial burns e Inability to consume orally ≥80% of required energy – Critical illness: coma, mechanical ventilation f Total feeding time >4 h/day in a disabled patient – Severe gastroesophageal reflux – Psychiatric disorders: food aversion, anorexia, depression 2 Disorders of digestion and absorption – Cystic fibrosis drolyzed cornstarch or corn syrup are commonly – Short bowel syndrome used, while proteins mostly originate from cow’s – Inflammatory bowel disease milk (casein or whey) or soybeans. Lipids are ad- – Malabsorption syndrome due to food intolerances ministered predominantly as long-chain fatty and allergy – Enteritis due to chronic infection acid based triglycerides (LCTs), or mixed with (Giardia lamblia, protozoa, etc.) medium-chain fatty acid triglycerides (MCTs). – Protracted diarrhea of infancy When compared with LCTs, MCTs are rapidly – Pancreatic insufficiencies hydrolyzed and absorbed directly into the portal – Severe primary or acquired immunodeficiency – Chronic liver disease circulation, even at low concentrations of pancre- – Graft-versus-host disease atic enzymes and bile acids. However, the energy – Intestinal fistulae content is lower, osmolality is higher, and they – Disorders of gastrointestinal motility with contain no essential fatty acids (EFAs). MCT- pseudo-obstruction based enteral formulas include up to 50% of EFA- 3 Increased nutritional requirements and losses 3 rich LCTs. A standard pediatric formula contains – Cystic fibrosis 40–55% of energy from carbohydrates, 10–15% – Chronic solid organ diseases: renal, heart, liver, lungs from proteins, and 30–40% from lipids, and the – Multiple trauma, extensive burns majority of them are free of gluten and lactose. 4 Growth failure or chronic malnutrition Polymeric formulas provide intact proteins. If (in addition to above) proteins are hydrolyzed to an extent that can be – Non-organic failure tolerated by at least 90% of patients with verified – Food deprivation allergy to the nitrogen source, the formula is 5 Altered metabolism and metabolic inborn errors called semi-elemental or oligomeric [5] . Mono- 6 Primary disease management (Crohn’s disease) meric/elemental formulas are nutritionally complete solutions containing amino acids, oligosaccharides, and fats as a mixture of LCTs and MCTs. A comparison of different types of formulas is presented in table 3. clinical condition of the patient; (b) history of In enteral formula selection, the following food intolerances or allergy; (c) level of intestinal factors should be considered: (a) nutrients and function; (d) site and route of formula delivery; energy requirements adjusted to the age and (e) formula characteristics such as osmolality,

Enteral Nutrition Support 143 Table 3. Comparison of different enteral formulas

Polymeric formulas Oligomeric formulas Monomeric formulas

Protein content, g/l 30–80 20–50 19.5–25 Nitrogen source Polypetides Small peptides Amino acids Carbohydrate content, g/l 90–200 100–200 81–146 Fat content, g/l 20–90 5–20 35 Caloric density, kcal/ml 1–2 1–1.7 0.67–1 Osmolarity, mosm/l 300 300–500 300–600 Advantages Palatable, cheap Hypoallergenic, Non-allergenic, easily absorbed immunomodulatory Disadvantages Requires intact gut, allergenic Bitter taste, expensive Hyperosmolar, expensive

viscosity and nutrient density; (f) taste prefer- Routes of Delivery ence, and (g) cost. There are many specialized If the expected duration of EN is short ( !6–8 and disease-specific formulas, but for the great weeks), it is preferentially delivered by NG or na- majority of pediatric patients, standard poly- soenteric tube, but if the expected duration is lon- meric formula is sufficient and well tolerated, ger, a feeding gastro/jejunostomy is recommend- with the best cost-benefit ratio. ed, which is placed by endoscopy as the quickest and cheapest procedure with a low rate of complications [6, 7] . Administration of EN Among the different tubes, those made of polyvinyl chloride (PVC) are the least desirable Sites of Delivery because of the possible release of potentially tox- EN can be administered either into the stomach ic phthalate esters into the lipid-containing or into the proximal small intestine depending feeds, and if left in place for 1 4 days they may on: (a) gut status; (b) expected duration of EN, become rigid and cause lesions of the upper gas- and (c) anticipated risk for aspiration. Among trointestinal tract [8] . Silicon and polyurethane the two sites, intragastric feeding is associated tubes are more convenient, and can be safely with a more flexible feeding schedule, larger vol- kept in place for several weeks. Considering the ume and higher osmotic tolerance, lower fre- required length of the NG tube, it should equal quency of diarrhea and of dumping syndrome the distance between nose and the umbilicus. due to: (a) stimulation of normal digestive and Placement into the stomach is confirmed by epi- hormonal responses; (b) antimicrobial proper- gastric auscultation during injection of air, ac- ties; (c) tubes are more easily placed, and (d) the companied by measuring the pH of the aspirate stomach serves as a reservoir gradually releasing which should be bellow 4. However, radiologic nutrients. However, if there is acute pancreatitis confirmation must be obtained when: (a) the pH or a high risk for aspiration, intrajejunal feeding of aspirate is 1 5; (b) an aspirate cannot be ob- is the preferred method. Transpyloric (intrajeju- tained, and (c) the patient’s condition changes nal) feeding should never be provided as an in- du ri ng NG t ube i nser t ion w it h prolonged coug h- termittent (bolus) feeding but always as a con- ing, restlessness and discomfort or hoarseness tinuous feeding. [9] .

144 Pediatric Nutrition in Practice Table 4. Enteral feeding complications and preventive and therapeutic measures [12]

Complications Prevention and treatment

Gastrointestinal Formula selection Diarrhea, nausea, vomiting, bloating, Polymeric vs. pre-digested abdominal distension Disease specific Technical Feeding techniques Occlusion, migration Bolus vs. continuous Metabolic Gradual initiation of EN Fluid, glucose and electrolyte imbalance EN administration Infective Delivery site (stomach vs. jejunum) Gastroenteritis, septicemia Delivery route (tube vs. stoma) Psychological Monitoring Oral aversion, altered body self-image Growth (weight, height/length, skinfolds) Hematology, biochemistry Multidisciplinary team approach Protocol application and quality control Others Tube selection (PVC vs. silicon), maintenance

Modes to Deliver EN Monitoring and Complications EN delivery modes are intermittent, continuous and combined. Intermittent (bolus) delivery is Patients receiving EN should be monitored regu- physiologically more adequate, but in patients larly for growth, fluid, energy and nutrient in- with a very impaired gut, continuous feeding is take, therapeutic efficacy, and blood and bio- beneficial due to the lower thermogenic effect chemical changes. and improved substrate utility. An appropriate Possible complications and preventive mea- 3 and constant flow can be ensured by using a sures are listed in table 4 . Their occurrence can peristaltic enteral pump. When the child can eat, be minimized by: (a) avoidance of drip feeding both methods of feed delivery can be combined, and blenderized feeds; (b) using silicon and poly- with tube feeding overnight for 10–12 h and oral urethane NG tubes; (c) gradual initiation and intake during the day. This combination pre- stepwise increase in volume and concentration; serves sensory and motor oral functions. (d) regular monitoring of residual gastric volumes; (e) strict adherence to management proto- Initiation of EN cols, and (f) close supervision by a dedicated mul- Initiation of EN should be gradual, depending tidisciplinary team [3, 10] . on: (a) age; (b) clinical condition and gut status; Despite the broad range of potential complica- (c) formula choice (polymeric versus elemental), tions EN is a well-established, safe and effective and (d) route of delivery (stomach versus jeju- method of improving a patient’s clinical condi- num). A slow stepwise increase in volume and tion, nutritional status and growth, particularly concentration is particularly important for pa- if procedural protocols are followed, and regular tients with grossly impaired intestinal func- quality control is applied [11] . tion.

Enteral Nutrition Support 145 Conclusions • Selection of enteral formula depends on the age and clinical condition, but for the majority • Enteral nutrition is a safe and effective meth- of patients a standard polymeric formula is od of nutritional therapy the appropriate choice, with the best cost-ben- • Enteral nutrition should be used when oral efit ratio feeds cannot sustain normal growth in a child • Technical, metabolic, gastrointestinal, infec- with a reasonably preserved gastrointestinal tive and psychological complications may oc- function cur; close monitoring by a multidisciplinary team, application of procedural protocols, and regular quality control are therefore required

References

1 Axelrod D, Kazmerski K, Iyer K: Pedi- 5 American Academy of Pediatrics Com- 8 Goulet O, Koletzko B: Nutritional sup- atric enteral nutrition. JPEN J Parenter mittee on Nutrition: Hypoallergenic port in children and adolescents; in

Enteral Nutr 2006; 30:S21–S26. infant formulas. Pediatrics 2000; 106: Sobotka L (ed): Basics in Clinical Nutri- 2 Develuy W, Guimber D, Mention K, et 346–349. tion, ed 3. Prague, Galen, 2004, pp al: Home enteral nutrition in children: 6 Löser C, Aschl G, Hebuterne X, et al: 439–454. an 11-years experience with 416 pa- ESPEN guidelines on artificial enteral 9 Richardson DS, Branowicki PA, Zeid-

tients. Clin Nutr 2005; 24: 48–54. nutrition – percutaneous endoscopic man-Rogers L, et al: An evidence-based

3 Agostoni C, Axelsson I, Colomb V, et al: gastrostomy (PEG). Clin Nutr 2005; 24: approach to nasogastric tube manage- The need for nutrition support teams 848–861. ment: special considerations. J Pediatr

in pediatric units. A commentary by 7 Raval MV, Phillips JD: Optimal enteral Nurs 2006; 21: 388–393. the ESPGHAN Committee on Nutri- feeding in children with gastric dys- 10 Roy S, Rigal M, Doit C, et al: Bacterial

tion. J Pediatr Gastroenterol Nutr 2005; function: surgical jejunostomy vs. contamination of enteral nutrition in a

41: 8–11. image-guided gastrojejunal tube pediatric hospital. J Hosp Infect 2005;

4 Zadak Z, Kent-Smith L: Commercially placement. J Pediatr Surg 2006; 41: 59: 311–316. prepared formula; in Sobotka L (ed): 1679–1682. 11 Jeejeebhoy KJ: Enteral feeding. Curr

Basics in Clinical Nutrition, ed 3. Opin Gastroenterol 2005; 21: 187–191. Prague, Galen, 2004, pp 221–227. 12 Atten MJ, Skipper A, Kumar S, et al: Enteral nutrition support. Dis Mon

2002; 48: 749–782.

146 Pediatric Nutrition in Practice Koletzko B. (ed): Pediatric Nutrition in Practice. Basel, Karger, 2008, pp 147–150

3 Nutritional Challenges in Special Conditions and Diseases

3.4 Parenteral Nutrition Support Berthold Koletzko

Key Words tion is more costly and carries greater risks than Parenteral feeding ؒ Intravenous alimentation ؒ oral or enteral nutrition. Parenteral feeding is not Substrate requirements, parenteral indicated in patients with adequate small intestine function in whom oral tube or gastrostomy feeding can be used. Exactly when parenteral nu- Key Messages trition should be initiated depends both on indi- R Parenteral nutrition is indicated when adequate vidual circumstances and the patient’s age and nutrition cannot be provided orally or enterally size. In small preterm infants, starvation for just R Parenteral nutrition is not indicated in patients 1 day may be detrimental, and parenteral feeding with adequate small intestine function who can be must be instituted shortly after birth if it is obvi- enterally (tube) fed R Ordering and monitoring of parenteral feeding ous that enteral nutrition will not be tolerated should follow agreed algorithms to improve qual- soon. In older children and adolescents, longer ity of care periods of inadequate nutrition (up to 7 days) R Patients receiving parenteral nutrition should be may be tolerated, depending on the disease, age evaluated 2–3 times/week, e.g. clinical examina- and nutritional status of the patient, and type 3 tion, weight, anthropometry, laboratory values, di- of intervention (surgery or medical). Whenever etary intake as appropriate R The available evidence-based guidelines on pedi- possible, parenteral nutrition should be com- atric parenteral nutrition should guide practice, in- bined with some (at least minimal) enteral nutri- cluding dosage of substrate supply tion. Establishing a multidisciplinary pediatric Copyright © 2008 S. Karger AG, Basel nutrition support team for supervision of parenteral nutrition can improve the quality of care and save costs, hence it is highly recommended [1] . Ordering and monitoring parenteral nutri- Introduction tion should follow agreed algorithms to improve quality of care. Patients should be evaluated 2–3 Parenteral nutrition is generally indicated when times/week, e.g. clinical examination, weight, an- adequate nutrition cannot be provided orally or thropometry, laboratory values, dietary intake enterally, to prevent or correct malnutrition, and as appropriate. The recommendations provided to sustain appropriate growth. It should be avoid- here are based on the evidence-based Guidelines ed whenever possible through adequate care, spe- for Pediatric Parenteral Nutrition [2] . cialized enteral nutrition and artificial feeding Recommendations on parenteral substrate sup- devices as appropriate, because parenteral nutri- ply to stable patients are summarized in table 1 . Table 1. Recommended usual dosages for parenteral substrate supply to stable patients by age

Age group Water Energy Amino Glu- Lipids, g Sodium Potas- Calcium Phospho- Magne- ml/kg kcal/kg acids cose trigly- mmol/kg sium mmol/kg rus sium g/kg g/kg cerides/kg mmol/kg mmol/kg mmol/kg

Preterm 140–160 110–120 1.5–4 18 up to 3–4 3–5 (–7) 2–5 Neonate (1st 140–160 90–100 1.5–3 18 up to 3–4 2–3 1.5–3 month) 0–1 years 120–150 90–100 1–2.5 16–18 up to 3–4 2–3 1–3 0–6 months: 0.8 0.5 0.2 (max. 180) 7–12 months: 0.5 1–2 years 80–120 75–90 1–2 1–3 up to 2–3 1–3 1–3 0.2 0.2 0.1 (max.150) 3–6 years 80–100 75–90 1–2 1–3 up to 2–3 1–3 1–3 0.2 0.2 0.1 7–12 years 60–80 60–75 1–2 1–3 up to 2–3 1–3 1–3 0.2 0.2 0.1 13–18 years 50–70 30–60 1–2 1–3 up to 2–3 1–3 1–3 0.2 0.2 0.1

Depending on the condition and individual needs of the patient, different dosages may be required. Adapted from Koletzko et al. [2]. Reproduced with kind permission from Wolters Kluwer. K+ supplementation should usually start after onset of diuresis. Chloride supply usually equals the sum of sodium and potassium supply.

Table 2. Recommended standard parenteral fluid supply (ml)

Time after birth, days 123456

Term neonate 60–120 80–120 100–130 120–150 140–160 140–180 Preterm neonate >1,500 g 60–80 80–100 100–120 120–150 140–160 140–160 <1,500 g 80–90 100–110 120–130 130–150 140–160 160–180

In neonates, parenteral fluid supply should be gradually increased over the first days of life. Adapted from Koletzko et al. [2]. Reproduced with kind permission from Wolters Kluwer.

Table 3. Suggested increase in intravenous glucose sup- W a t e r ply (g/kg/day) over the first 4 days of parenteral nutrition Fluid needs vary markedly and must be adapted Child’s weight, kg Day 1 Day 2 Day 3 Day 4 to the individual patient’s condition. For exam- <3 10 14 16 18 ple, some renal or cardiac disorders require low- 3–10 8 12 14 16–18 er water intakes, whereas higher intakes are 10–15 6 8 10 12–14 needed with enhanced fluid losses (fever, hyper- 15–20 4 6 8 10–12 20–30 4 6 8 <12 ventilation, diarrhea or enhanced losses from >30 3 5 8 <10 wounds or fistulae). Monitoring fluid status is necessary, as well as clinical status, body weight, Adapted from Koletzko et al. [2]. Reproduced with kind and possibly water intake and excretion, blood permission from WoltersKluwer. electrolytes, acid base status, hematocrit, urine-

148 Pediatric Nutrition in Practice specific gravity and urine electrolytes. Postnatal day). Glucose infusion for term neonates and fluid supply should be gradually increased ( ta- children ^ 2 years should not exceed 13 mg/kg ble 2 ). per min (18 g/kg per day). Glucose intake should be adapted to the administration of drugs that impair glucose metabolism (e.g. steroids, soma- Energy tostatin analogues, tacrolimus). Very high glucose intakes and marked hyperglycemia should Energy needs vary with physical activity, growth be avoided because they may induce increased li- and the possible need to correct malnutrition. pogenesis and tissue fat deposition, liver steato- Energy supply can be adjusted based on formulae sis, enhanced CO 2 production, impaired protein for energy expenditure (see Chapter 1.3.2) and metabolism, and possibly increased infection-re- during weight changes. Low energy supplies in- lated morbidity and mortality [2] . In critically ill duce failure to thrive, but excessive energy intake and unstable patients, glucose dosage should be (‘hyperalimentation’) must be avoided because it lower and increased only according to the pa- may induce metabolic imbalances, liver damage tient’s condition and blood glucose levels. and, in malnutrition, re-feeding syndrome [3] .

Lipids Amino Acids Lipid emulsions supply essential fatty acids and Parenteral amino acid requirements are lower energy at iso-osmolarity. Lipids should generally than enteral needs because parenteral nutrition provide 25–40% of non-protein parenteral nutri- bypasses intestinal amino acid uptake and utili- tion calories. Parenteral lipid intake is usually lim- zation. Amino acid utilization requires an energy ited to 0.13–0.17 g/kg per h (3–4 g/kg per day) in supply of ;30–40 kcal per g of amino acids. In infants and 0.08–0.13 g/kg per h (2–3 g/kg per day) neonates requiring parenteral feeding, amino in children. A stepwise increase in lipid infusion acid supply should start on the first postnatal day. rates by 0.5–1 g/kg per day has not been shown to 3 Infants and young children should receive pedi- improve tolerance but allows monitoring for hy- atric amino acid solutions with adequate amounts pertriglyceridemia. Regular plasma triglyceride of cysteine, taurine and tyrosine (conditionally measurements are recommended during paren- essential; see Chapter 1.3.3). teral feeding, particularly in critically ill or infected patients. Dosage reduction should be considered at triglyceride concentrations during infusion Glucose 1 250 mg/dl in infants or 1400 mg/dl in children, but a minimum linoleic acid intake to prevent es- Glucose is the only carbohydrate recommended sential fatty acid deficiency should always be given for parenteral nutrition and should provide 60– (preterm infants 6 0.25 g linoleic acid/kg per day, 75% of non-protein calorie intake. During the term infants/children 6 0.1 g/kg per day). In neo- first days on parenteral feed, the glucose supply nates requiring parenteral nutrition, lipids can should be gradually increased (table 3). In pre- start on day 1 of life and should start no later than term infants glucose intake should begin with 4– day 3. In young infants, lipids should be adminis- 8 mg/kg per min (5.8–11.5 g/kg per day) and in- tered continuously over about 24 h. crease gradually. In critically ill children glucose During phototherapy validated light-protect- intake should be ^ 5 mg/kg per min (7.2 g/kg per ed tubing for lipid emulsions is recommended to

Parenteral Nutrition Support 149 decrease hydroperoxide formation. Lipid emul- The risks of parenteral nutrition are best re- sions have no demonstrable effect on hyperbili- duced by limiting the amount and duration [2, 5] . rubinemia. There is no firm evidence on adverse Persistent attempts should be made to increase effects in severe acute respiratory failure, but the amount of enteral feedings as tolerated. Rath- avoiding high lipid dosages in these patients ap- er than enteral starvation, minimal enteral feeds pears prudent. In severe, progressive parenteral should be given whenever possible, and an expe- nutrition-associated cholestasis, a decrease or rienced pediatrician and an experienced dieti- transient interruption of intravenous lipids cian should be involved. should be considered [2] . Commercial lipid emulsions based on soybean oil, or mixtures of olive and soybean oil, or C o n c l u s i o n s of medium-chain triglycerides and soybean oil are considered safe for pediatric parenteral feed- Parenteral Nutrition ing [2] . • is an essential and often life-saving treatment for infants and children who cannot be adequately fed orally or enterally O t h e r A s p e c t s • should only be used when all alternative options have been explored, including adequate Vitamins and minerals should be supplied with care, specialized enteral nutrition and artifi- all parenteral nutrition provided over several cial feeding devices days. Cyclical parenteral feeding (over 8–14 h/ • can induce severe adverse effects. The risk is day) should be considered from the age of 3–6 reduced by a meticulous approach, establish- months onwards [2, 4] . ment of a multidisciplinary nutrition support Individualized prescriptions of pediatric par- team, avoidance of unbalanced or excessive enteral nutrition are widely used, but standard substrate supplies, strict hygiene measures to solutions are suitable for many pediatric patients reduce catheter infections, concomitant mini- with adequate monitoring and the possible addi- mal enteral feeding and forceful enhancement tion of electrolytes/nutrients. Standard solutions of enteral feeding where possible to limit the can improve the quality and safety of parenteral amount and duration of parenteral feeding feeding and reduce costs.

References

1 Agostoni C, Axelsson I, Colomb V, 2 Koletzko B, Goulet O, Hunt J, Krohn K, 3 Kraft MD, Btaiche IF, Sacks GS: Review Goulet O, Koletzko B, Michaelsen KF, Shamir R; for the Parenteral Nutrition of the refeeding syndrome. Nutr Clin

Puntis J, Rigo J, Shamir R, Szajewska H, Guidelines Working Group: Guidelines Pract 2005; 20: 625–633. Turck D; ESPGHAN Committee on Nu- on Paediatric Parenteral Nutrition of 4 Goulet O, Koletzko B: Nutritional sup- trition; European Society for Paediatric the European Society of Paediatric Gas- port in children and adolescents; in Gastroenterology: The need for nutri- troenterology, Hepatology and Nutri- Sobotka L (ed): Basics in Clinical Nutri- tion support teams in pediatric units. A tion (ESPGHAN) and the European tion, ed 3. Prague, Galén, 2004, pp commentary by the ESPGHAN Com- Society for Clinical Nutrition and Me- 439–462. mittee on Nutrition. J Pediatr Gastro- tabolism (ESPEN), Supported by the 5 Koletzko B, Krohn K, Goulet O, Shamir

enterol Nutr 2005; 41: 8–11. European Society of Paediatric Re- R: Paediatric Parenteral Nutrition. A search (ESPR). J Pediatr Gastroenterol Practical Guide. Basel, Karger, 2008.

Nutr 2005; 41(suppl 2):S1–S87.

150 Pediatric Nutrition in Practice Koletzko B. (ed): Pediatric Nutrition in Practice. Basel, Karger, 2008, pp 151–154

3 Nutritional Challenges in Special Conditions and Diseases

3.5 Overweight and Obesity Martin Wabitsch

Key Words Obesity develops during periods of positive Overweight ؒ Obesity ؒ Dietary fat ؒ Sugar-added energy balance resulting from an inadequately beverages ؒ Energy density low regular physical activity and an inadequately high calorie intake. The fat and water contents of foods are the main determinants of the energy Key Messages density of the diet. A lower consumption of en- R Obesity develops during periods of positive ener- ergy-dense foods (i.e. high fat, high sugar and gy balance resulting from inadequately low regular high starch) and energy-dense drinks (i.e. sug- physical activity and inadequately high calorie in- ared drinks) contributes to a reduction in total take energy intake. Conversely, a higher intake of en- R Treatment of obesity in children can be performed on the basis of a behavioral-based training pro- ergy-diluted food (e.g. vegetables and fruit), high gram aiming at reducing sedentary behaviors, in- in non-starch polysaccharides (e.g. wholegrain creasing physical activity and improving energy cereals) contributes to a reduction in total energy intake intake and can also improve micronutrient sup- R Successful dietary measures are reducing the in- plies. take of energy-dense foods, foods with added sug- The eating and physical activity behaviors of 3 ars, and increasing the proportion of foods with high fiber content an individual child are strongly influenced by R Eating and physical activity behavior of an individ- environmental and social factors. Therefore, the ual child is strongly influenced by environmental recommendations given here will only have and social factors which also need to be changed limited success in an environment in which in order to achieve long-term success adequate physical activity is not supported and Copyright © 2008 S. Karger AG, Basel the consumption of high energy food is stimulated. Treatment of obesity in children can be per- Introduction formed with behavioral-based training programs aiming at increasing physical activity and mod- The prevalence of obesity has been increasing erating energy intake. Such a program should last during the last two decades in almost all coun- at least 6, better 12 months since changes in eat- tries (high and low income). Early treatment is ing and physical activity behavior take time and required due to the adverse consequences of obe- need to be stabilized. A variety of professionals sity, such as impaired glucose tolerance and dia- can accomplish many aspects of a training pro- betes, cardiovascular disease and hypertension, gram: nurses, nurse practitioners, nutritionists, orthopedic disease and cancer. physicians, psychologists, and social workers. The inclusion of parents and other persons of the F a t I n t a k e closer social environment is important for the long-term results of such a program. Programs Excessive consumption of fat is believed to be a can be performed in groups with 10 or 12 mem- causative factor for weight gain. Furthermore, bers. However, additional individualized coun- the adverse effects of saturated fat on the risk of seling is often required. cardiovascular disease are well documented. Di- At the beginning of a training program, a diets with limited fat content (no more than 30%) etary protocol can be helpful in describing the are helpful for weight management. individual’s dietary intake, including the situations in which meals are consumed. Further- more, a dietary protocol written during the train- Intake of Carbohydrates ing program may help to document the achieved goals and changes in dietary behavior. Modifica- A decrease in dietary fat will be accompanied by tion of dietary intake and behavior should be per- a compensatory increase in carbohydrate con- formed in small steps which are achievable by the sumption. This may occur especially in the form child and his/her parents. Regular contact of the of refined foods (e.g. breads, ready-to-eat cereals, parent and child with the trainer is essential to soft drinks, cakes, and others). Such eating review and reinforce the previous goals of a behavior might even increase body weight. By healthy diet and activity as well as implementa- contrast, the majority of studies show that a high tion of skills. It is important to include behavior intake of non-starch polysaccharides (dietary fi- therapy in the treatment of childhood obesity. ber) promotes weight loss. A weight-stimulating The addition of behavioral techniques of contin- effect of an increased consumption of sugar- gency contracting, self-monitoring of caloric in- sweetened soft drinks is well documented [5] . take and weight, praise and stimulus control to Furthermore, a decrease in the consumption of nutrition education significantly improves the sugar-sweetened soft drinks leads to relative treatment results [1] . weight loss. Obesity is a chronic disease requiring life-long attention to healthy eating and an active lifestyle. After an initial weight management program Energy Density both the child and parents must continue to work actively to maintain behaviors. The consumption of a diet with high energy den- Training programs for a parent or an adoles- sity may promote body weight gain [2]. There- cent who is not ready to change should be avoided fore, energy density is a critical factor determin- since they may not only be futile but also harm- ing energy intake. ful, because an unsuccessful program may diminish the child’s self-esteem and impair future efforts to improve weight. Portion Size The dietary goals for parents and their families are well-balanced, healthy meals and a healthy Older children (after infancy) are less responsive approach to eating. These changes should be con- to internal hunger and satiety cues and more re- sidered permanent rather than a temporary eat- active to environmental stimuli. Therefore, por- ing plan for rapid weight loss. In the following tion size is a critical factor determining energy paragraphs special dietary aspects and recom- intake. mendations [2–4] are summarized.

152 Pediatric Nutrition in Practice Table 1. Recommendations for obesity-preventive nutrition in infants, children, adolescents, and families

Recommendations for nutrition in infants – Promote breastfeeding – Avoid the use of very sweet infant formula and complementary feeds – Avoid the use of bottle feeding of energy-dense feeds (no more than 70 kcal/100 ml) Recommendations for young children (age 2–6 years) – Set regular meal times (e.g. 3 main meals, 2 snacks) – Provide a wide variety of nutrient-dense food, with an emphasis on fruit and vegetables; limit high energy- dense, nutrient-poor food such as salty snacks, ice cream, fried foods, cookies, and sweetened beverages – Parents should accept the child’s ability to regulate energy intake rather than feeding until the plate is empty – Pay attention to portion size, serve portions appropriate for the child’s size and age – Limit snacking during sedentary behavior or in response to boredom and particularly restrict use of sweetened beverages as snacks (e.g. juice, soda, sport drinks) – Have regular family meals to promote social interaction and role model food-related behavior – Parental role modeling is important in establishing children’s food choices. Depending on their own food choices, parents can be either positive or negative role models Recommendations for children and adolescents – Promote an active lifestyle – Limit television viewing – Promote the intake of fruit and vegetables – Restrict the intake of energy-dense, micronutrient-poor foods (e.g. packed snacks) – Restrict the intake of sugar-sweetened soft drinks Recommendations for modifying the child’s environment – Enhance physical activity in schools and communities – Create more opportunities for family interaction (e.g. eating family meals) – Limit the exposure of young children to heavy marketing practices of energy-dense, micronutrient-poor foods General recommendations for all patients and families – Eat only at meal times and recognized snack periods (define eating-free time periods during a day) – Eat, if possible, as a family or as a group. This may contribute satisfaction from a meal and psychological satiety 3 – Discourage eating in front of the television or snacking when playing or working with a video or computer – Food choices: Select whole food or raw unprocessed food whenever possible and prepare meals at home – Plan enough time for food intake. It is more time-consuming to eat whole foods, e.g. apples, compared with apple juice

Fast Food Family Factors

The rising consumption of fast food in developed Parent–child interaction and the home environ- and developing nations might have particular ment can affect behaviors related to body weight relevance to the childhood obesity epidemic. development. Social support from parents and This association might be due to the fact that fast others correlate strongly with the participation in food typically has a high glycemic index and a physical activity and healthy dietary behaviors. high energy density and is served in large portion Access and exposure to a range of fruits and veg- sizes. Additionally, these foods tend to be low in etables at home is important for the development fiber, micronutrients and antioxidants [2] . of preferences for these foods.

Overweight and Obesity 153 School Environment C o n c l u s i o n s

School environment is important and influences • Treatment of obesity in children can be per- nutrition knowledge, eating patterns and physi- formed on the basis of a behavioral-based cal activity behavior as well as sedentary behav- training program aiming at increasing physi- iors. School-based programs for weight control cal activity and improving energy intake in can be effective [6] . order to achieve long-term weight mainte- Recommendations for nutrition in infants, nance and allowing adequate nutrition for children, adolescents, and families are given in growth and development table 1 . Moreover, daily physical activity should • The inclusion of parents is important for the be emphasized, aiming at a moderate physical ac- long-term results tivity of at least 1 h/day. Sedentary behaviors • Successful dietary measures are: reducing the should be limited, with no more than about 1 h/ intake of energy-dense food and food with day of video screen/television time. The place- added sugars, as well as increasing the intake ment of television sets in children’s rooms/bed- of food with high fiber content rooms should be discouraged. • Eating and physical activity behavior of an individual child is strongly influenced by environmental and social factors. Therefore, treatment will have only limited success in an environment where adequate physical activity is inhibited and the consumption of high energy food is stimulated

References

1 Epstein LH, Myers MD, Raynor HA, 3 Gidding SS, Dennison BA, Birch LL, et 5 Malik SV, Schulze MB, Hu FB: Intake of Saelens BE: Treatment of pediatric obe- al: Dietary recommendations for chil- sugar-sweetened beverages and weight

sity. Pediatrics 1998; 101: 554–570. dren and adolescents: a guide for prac- gain: a systematic review. Am J Clin

2 Ebbeling CB, Pawlak DB, Ludwig DS: titioners: consensus statement from the Nutr 2006; 84: 274–288. Childhood obesity: public-health crisis, American Heart Association. Circula- 6 Sharma M: School-based interventions

common sense cure. Lancet 2002; 360: tion 2005; 112: 2061–2075. for childhood and adolescent obesity.

473–482. 4 Barlow SE, Dietz WH: Obesity evalua- Obes Rev 2006; 7: 261–269. tion and treatment: expert committee

recommendations. Pediatrics 1998; 102: e29.

154 Pediatric Nutrition in Practice Koletzko B. (ed): Pediatric Nutrition in Practice. Basel, Karger, 2008, pp 155–161

3 Nutritional Challenges in Special Conditions and Diseases

3.6 Acute and Chronic Diarrhea Zulfiqar Bhutta

Key Words first week of the illness and more severe acute ep- -Diarrhea, persistent ؒ Child mortality ؒ Preventive isodes leading to child deaths [4] . A smaller pro strategies, diarrhea ؒ Breastfeeding ؒ Nutrition portion of diarrheal illnesses fail to resolve and rehabilitation persist for longer than 2 weeks [5] . These episodes of persistent diarrhea (PD) have been defined as episodes that began acutely but lasted for at least Key Messages 14 days [6] and have been shown to identify chil- R Despite major advances, diarrheal disorders still dren with a substantially increased diarrheal kill 1.8 million children worldwide, mostly in devel- burden and between 36 and 54% of all diarrhea- oping countries related deaths [7] . R We have the know how and the interventions that can make a difference provided they are made Globally, infections represent the most im- available to all children in need portant cause of acute diarrhea in children. Al- Copyright © 2008 S. Karger AG, Basel though poverty, poor water and sanitation repre- 3 sent fundamental risks, immediate risk factors for diarrhea include low birthweight, failure to Introduction breastfeed, inappropriate complementary foods and associated micronutrient deficiencies (espe- Despite considerable advances in the under- cially vitamin A and zinc) [8] . The major patho- standing and management of diarrheal disorders gens causing acute diarrhea are detailed in tain childhood, they are still globally responsible ble 1 and the common clinical syndromes asso- for a major number of childhood deaths, estimat- ciated with pathogens causing diarrhea are listed ed at 1.8 million deaths [1, 2] . While the global in table 2 . mortality for diarrhea has been reduced, the in- It is also important to highlight that in addi- cidence remains unchanged at about 3.2 episodes tion to the large proportion of acute diarrhea ep- per child year [3] . Young children, especially if isodes that relate to rotavirus diarrhea, it is esti- malnourished and immunocompromised, are at mated that almost a quarter of all diarrhea deaths greatest risk for more severe disease and compli- may be associated with dysentery, and a large cations. proportion caused by Shigella organisms [9, 10] . Most diarrheal disorders form a continuum, Additional factors underlying the increased with the majority of cases resolving within the propensity to infection and poor intestinal repair Table 1. Infectious agents causing diarrhea in children

Bacteria producing Bacteria producing Viruses Parasites inflammatory diarrhea non-inflammatory diarrhea

Clostridium perfringens Enteropathogenic Astrovirus Balantidium coli Escherichia coli Clostridium difficile Vibrio cholerae 01 and 0139 Enteric adenovirus Cryptosporidium parvum Enteroinvasive E. coli Cyclospora cayetanensis Yersinia enterocolitica Encephalitozoon intestinalis Plesiomonas shigelloides Enterotoxigenic E. coli Calicivirus Entamoeba histolytica Campylobacter jejuni Rotavirus Enterocytozoon bieneusi Vibrio parahaemolyticus Staphylococcus aureus Cytomegalovirus Giardia lamblia Aeromonas V. parahaemolyticus Isospora belli Shigella Enterotoxigenic E. coli Strongyloides stercoralis E. coli O157:H7 Herpes simplex virus Trichuris trichiura Salmonella Norwalk agent-like virus

may include key micronutrient deficiencies that tant that these are prevented. Thus, in popula- may influence this process. These may include tions at risk, the promotion of early and exclusive both zinc and multiple micronutrient deficien- breastfeeding for at least 6 months, avoidance of cies [11] . These findings clearly have enormous formula feeding, timely and adequate weaning implications for the preventive and therapeutic with hygienic nutritious foods will help to pre- approaches to diarrhea. vent episodes of diarrhea. A combination of allocation of appropriate resources for public health and basic needs, staff training and community Prevention of Diarrhea mobilization is necessary to reduce the global burden of diarrhea. Of various interventions that can prevent diar- In recent years the development and availabil- rhea among children in the developing world, ity of effective rotavirus vaccines offer a unique provision of safe water and hygiene interventions opportunity for reducing the burden and severity are critical. It has been estimated that combined of diarrhea [12] with a protective efficacy ap- hand washing promotion, provision of safe water proaching 80% for severe acute dehydrating diar- and sanitation interventions can lead to an at rhea requiring hospitalization. least 33% reduction in diarrhea (RR = 0.67; 95% CI 0.59, 0.76) [8, 11] . Other preventive interventions include exclu- Management of Acute and Persistent sive breastfeeding and safe complementary feed- Diarrhea ing strategies to prevent diarrhea. Early and unhygienic introduction of milk other than breast Oral rehydration therapy is the mainstay in the milk and recurrent acute diarrheal episodes that treatment of diarrheal episodes, and in recent are poorly managed are important predisposing years low osmolality oral rehydration solution factors to the development of PD, and it is impor- has been recommended for rehydration [13] . In

156 Pediatric Nutrition in Practice Table 2. Diarrhea pathogens and clinical syndromes in children

Pathogen Site of action Incubation Clinical features period

Enteropathogenic Proximal small 6–48 h Self-limiting watery diarrhea Escherichia coli EPEC intestine Occasional fever and vomiting Enteroinvasive Distal ileum 1–3 days Watery diarrhea, occasionally bloody diarrhea E. coli EIEC and colon Enteroaggregative Small intestine 8–18 h Watery, mucoid diarrhea E. coli EAEC Bloody diarrhea in 30% Enterohemorrhagic Colon 3–9 days Abdominal pain, vomiting, bloody diarrhea E. coli EHEC Hemolyic uremic syndrome in 10% Enterotoxigenic Small intestine 14–30 h Watery diarrhea, fever, abdominal pain and vomiting E. coli ETEC Diffusely adherent Small intestine 6–48 h Mild watery diarrhea E. coli Shigella Colon 16–72 h Mucoid and bloody diarrhea (may be watery initially), fever, toxicity, tenesmus Yersinia enterocolitica Terminal ileum 4–6 days Watery or mucoid diarrhea (bloody in <10%) with abdominal pain, fever, bacteremia in young infants Campylobacter Small intestine 2–4 days Abdominal pain (frequently right-sided), watery diarrhea (occasionally mucoid and bloody), fever Rotavirus Small intestine 1–3 days Mostly in young children. May be mild diarrhea, typically acute watery diarrhea with upper respiratory symptoms in some children. Recognized as the main cause of severe dehydrating diarrhea in children 3

addition, the use of zinc supplements (10–20 mg/ The management of PD in malnourished day for 10–14 days) is recommended as the main- children is based on the principles of manage- stay in the treatment of acute diarrheal episodes ment of diarrhea and malnutrition. While a sub- [14] . In addition to these measures, continued ap- group may be severely malnourished requiring propriate enteral feeding of these children during rapid nutritional rehabilitation, often in hospi- diarrheal episodes accelerates clinical recovery tal, in other cases ambulatory management may from diarrhea. A proportion of cases who fail to be possible. Given the long time it may take to respond adequately and continue to purge must recovery, prolonged hospitalization may be quite be triaged for immediate assessment and appro- problematic in developing countries and, when- priate therapy. It must be underscored that the ever possible, ambulatory or home-based thera- most important factor for the prevention of pro- py using culturally acceptable diets must be longed episodes of diarrhea is the appropriate stressed [15] . recognition and management of acute diarrheal The following represent the basic principles in episodes. the prevention and management of PD and a sug-

Acute and Chronic Diarrhea 157 Acute diarrhea

Continued breastfeeding Low osmolality ORS Persistent diarrhea Zinc supplementation (10–20 mg orally for 10 days) (diarrhea ≥14 days)

Severe dehydration Recovery Assessment, resuscitation and early stabilization

Intravenous and/or oral rehydration (hypo-osmolar ORS) Treat electrolyte imbalance Screen and treat associated systemic infections

Continued breastfeeding Reduced lactose load by • Milk-cereal (usually rice-based) diet or • Replacement of milk with yogurt • Micronutrient supplementation (zinc, vitamin A, folate)

Recovery Continued or recurrent diarrhea Poor weight gain

Follow-up for growth Reinvestigate for infections Second-line dietary therapy (comminuted chicken or elemental diets)

Continued diarrhea and dehydration

Fig. 1. Suggested algorithm for the Reinvestigate to exclude intractable diarrhea of infancy Intravenous hyperalimentation management of diarrhea. ORS = Oral rehydration solution.

gested therapeutic approach is summarized in screened for at admission and rapidly treated. In the figure 1. severely ill malnourished children requiring hospitalization, broad-spectrum antibiotics at initial Initial Resuscitation and Stabilization admission and stabilization may be empirically Most children with PD and associated malnutri- started while awaiting cultures, but prolonged tion are not severely dehydrated and oral rehy- courses of antibiotics exceeding 7 days must be dration with low osmolality oral rehydration so- avoided. lution may be adequate. However, acute exacerbations and associated vomiting may require Enteral Feeding and Diet Selection brief periods of intravenous rehydration with Given that PD only rarely occurs in breastfed Ringer’s lactate. Acute electrolyte imbalance, infants, any amount of breastfeeding must be such as hypokalemia, and severe acidosis require continued, even in HIV-affected populations correction. More importantly, associated system- [16] . Despite mucosal abnormalities and diminu- ic infections have been recognized in severely tion in digestive and absorptive mechanisms, malnourished children with PD and must be most children with PD have adequate absorption

158 Pediatric Nutrition in Practice capacity and tolerate enteral feeding. In general, Follow-Up and Continued Nutritional therefore, withdrawal of milk and replacement Rehabilitation in Community Settings with specialized (and expensive) lactose-free for- Given the high rates of relapse in most children mulations is unnecessary. Most children with PD with PD and the association with severe acute are not lactose-intolerant, but some reduction in malnutrition, it is important to address the un- lactose load to under 5 g/kg/day may be prudent derlying risk factors and institute preventive [15] . Alternative strategies for reducing the lac- measures. These include appropriate feeding tose load in malnourished children with PD in- (breastfeeding, complementary feeding) and clude addition of milk to cereals as well as re- close attention to environmental hygiene and placement of milk with fermented milk products sanitation. This poses a considerable challenge in such as yogurt. communities deprived of basic necessities such as In rare instances when dietary intolerance clean water and sewage disposal in which recur- precludes the administration of cow’s milk-based rence of diarrhea is a distinct possibility. formulations or milk, it may be necessary to ad- In addition to the preventive aspects, the chal- minister specialized milk-free diets such as a lenge in most settings is to develop and sustain a comminuted or blenderized chicken-based diet form of dietary therapy using inexpensive, home- or an elemental formulation. The usual energy available and culturally acceptable ingredients density of any diet used for the therapy of PD which can be used to manage children with PD. should be around 1 kcal/g, aiming to provide an Given that the majority of cases of PD occur in energy intake of minimum 100 kcal/kg/day, and the community and that parents are frequently a protein intake of between 2 and 3 g/kg/day. The hesitant to seek institutional help, there is a need commonly used rice-lentil formulations in South to develop and implement inexpensive and prac- Asia such as khitchri provide this energy density tical home-based therapeutic measures. Avail- in combination with an optimal protein intake able evidence indicates that it may be entirely fea- and amino acid ratio [17] . sible to do so in community settings using either home-available foods or inexpensive locally Micronutrient Supplementation prepared ready-to-use therapeutic formulations 3 Most malnourished children with PD have asso- [18] . ciated deficiencies of micronutrients including Providing essential preventive and therapeu- zinc, iron and vitamin A. This may be a conse- tic interventions to reduce childhood diarrhea in quence of poor intake and continued enteral loss- health systems is necessary in order to achieve es, and while the evidence supporting zinc ad- the millennium development goals of reducing ministration in children with PD is persuasive, it child mortality by two thirds by the year 2015. is likely that these children have multiple micro- Early and unhygienic introduction of milk other nutrient deficiencies. This may be of particular than breast milk and recurrent acute diarrheal relevance in HIV endemic subjects. It is therefore episodes that are poorly managed are important important to ensure that all children with PD and predisposing factors in the development of pro- malnutrition receive an initial dose of 100,000 longed diarrhea and must be prevented. These units vitamin A and a daily intake of at least 3–5 risk factors are generally prevalent in poor com- mg/kg/day of elemental zinc. It is now recom- munities, and both poverty alleviation and social mended that all children with diarrhea receive a sector support mechanisms are fundamentally daily dose of 20 mg zinc for 10–14 days. important. A combination of allocation of appropriate resources for public health and basic needs, staff training and community mobilization is

Acute and Chronic Diarrhea 159 necessary to reduce the global burden of diar- Conclusions rhea. In many parts of the developing world it is important that these strategies are coupled with • Despite vast advances in our understanding of efforts to address the underlying social determi- the etiology and pathogenesis of diarrhea, nants of disease, poverty alleviation and an eq- acute and persistent diarrhea is still responsi- uity focus on addressing maternal and child ble for about 1.8 million child deaths annu- health. In poor communities and health systems ally with limited resources, the following preventive • The preventive strategies for acute and persis- strategies need to be introduced at scale: tent diarrhea are well recognized and include, (1) Promotion of early initiation and exclusive for populations at risk, exclusive breastfeeding breastfeeding for at least 6 months. for the first 6 months, followed by appropriate (2) Promotion of safe water, hygiene and hand complementary feeding strategies washing at the household level. • Recent advances in the management of diar- (3) Adequate sanitation and waste disposal rhea, including the use of reduced osmolality strategies [19] . oral rehydration solution and zinc supple- (4) Timely and adequate weaning with hygienic ments and appropriate use of antibiotics for nutritious foods. bacterial diarrhea when needed, may signifi- (5) Prompt care seeking for diarrheal episodes cantly improve diarrhea outcomes and must and standard case management with low be made available universally osmolality oral rehydration solution, zinc and • Rotavirus vaccination strategies offer a unique adequate dietary therapy. opportunity to considerably reduce severe (6) Vaccination strategies with measles and acute diarrhea-related morbidity and mortal- rotavirus vaccine. ity

References

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cet 2005; 365: 1147–1152. malabsorption: Working Group report Working paper No. 140. Cambridge, 2 Black RE, Morris SS, Bryce J: Where of the second World Congress of Harvard University, 2007. and why are 10 million children dying Pediatric Gastroenterology, Hepa- 9 Kotloff KL, Winickoff JP, Ivanoff B, et

every year? Lancet 2003; 361: 2226– tology, and Nutrition. J Pediatr Gastro- al: Global burden of Shigella infections:

2234. enterol Nutr 2004; 39(suppl 2):S711– implications for vaccine development 3 Kosek M, Bern C, Guerrant RL: The S716. and implementation of control strate-

global burden of diarrheal disease as 6 Anonymous: Persistent diarrhoea in gies. Bull World Health Organ 1999; 77: estimated from studies published be- children in developing countries: 651–666. tween 1990 and 2000. Bull World memorandum from a WHO Meeting. 10 Ahmed F, Ansaruzzaman M, Haque E,

Health Org 2003; 81: 197–204. Bull World Health Organ 1988; 66: 709– et al: Epidemiology of post-shigellosis 4 Parashar UD, Gibson CJ, Bresse JS, 717. persistent diarrhea in young children.

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hood diarrhea. Emerg Infect Dis 2006; al: Persistent diarrhea signals a critical 11 Fewtrell L, Kaufmann RB, Kay D, et al:

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Acute and Chronic Diarrhea 161 Koletzko B. (ed): Pediatric Nutrition in Practice. Basel, Karger, 2008, pp 162–167

3 Nutritional Challenges in Special Conditions and Diseases

3.7 HIV and AIDS Haroon Saloojee ؒ Peter Cooper

Introduction Key Words ؒ HIV ؒ AIDS ؒ Nutrition ؒ Feeding ؒ Breastfeeding Replacement feeding ؒ Complementary feeding ؒ Infants born to HIV-positive women have lower ,Malnutrition ؒ Micronutrients birthweights related to a lower gestational age high viral loads and the effect of HIV on the mother herself [1] . Key Messages Transmission through breastfeeding may ac- R HIV infection has greater nutritional consequences count for up to half of the HIV infections in infor children compared to adults, simply because fants and young children (over 300,000 infec- children have the additional nutritional demands tions annually). The rate of HIV infection in of growth and development breastfed infants is cumulative and roughly con- R Balancing the risks of HIV transmission through breastfeeding with the risks of not breastfeeding stant throughout the breastfeeding period. The in settings where access to safe replacement foods, overall risk of breastfeeding transmission is esti- healthcare and support are limited is one of the mated as 8.9 transmissions/100 child years of most difficult issues facing HIV-affected families breastfeeding (or about 0.74% per month of R When replacement feeding is acceptable, feasible, breastfeeding) [2] . affordable, sustainable and safe, avoidance of all breastfeeding by HIV-infected mothers is recom- The risk of transmission of HIV through mended. Otherwise, exclusive breastfeeding is rec- breastfeeding varies in relation to maternal clini- ommended during the first 6 months of life cal and immunological status, plasma and breast R Micronutrient deficiencies are common in HIV-in- milk viral load and possibly breast health (sub- fected children, accelerating progression of HIV clinical or clinical mastitis, cracked nipples, etc.) disease, which in turn leads to worsened nutrition- [3] . al status R Antiretroviral (HAART) therapy is associated with Feeding recommendations for infants of HIV- improvements in weight, weight-for-height, mid- infected mothers in resource-poor settings re- arm circumference and lean body mass in HIV-in- main controversial. The most appropriate infant fected children Copyright © 2008 S. Karger AG, Basel feeding option continues to depend on the mother’s individual circumstances, including her health status and the local situation. HIV infection in children can lead to poor weight gain, failure to thrive, slowed linear growth (stunting) and wasting through decreased tions of exclusive breastfeeding and replacement nutrient intake, gastrointestinal malabsorption, milk for infants of HIV-infected mothers (ta- increased utilization, tissue catabolism and psy- ble 2 ). chosocial factors (such as an unstable home environment). Higher viral load has been associated B r e a s t f e e d i n g with a greater risk of growth failure. Strategies which should be employed to mini- Micronutrient deficiencies (such as vitamin mize the risk of transmission during breastfeed- A, selenium and zinc) are common and may ac- ing are outlined in table 3 . celerate progression of HIV disease, which in turn leads to worsened nutritional status. Replacement Feeding Children with HIV and AIDS require high- Replacement feeding requires substituting breast energy, nutrient-dense diets and may require up milk with replacement milk (i.e. infant formula) to 200% of the recommended daily allowance. before 6 months and with solid foods after 6 There are insufficient data to support a routine months. Safely prepared exclusive commercial increase in protein intake. Fat requirements are infant formula will meet all the nutrient needs of unchanged. the HIV-exposed infant if fed in amounts calculated to meet the infant’s energy requirements. Mothers who have recently been infected, have Feeding the HIV-Exposed Infant progressed to AIDS, or whose CD4 counts are below 200/ ␮l, should be encouraged to consider re- The current WHO recommendations on infant placement feeding (to reduce the high transmis- feeding by HIV-infected mothers state: ‘When sion risk). replacement feeding is acceptable, feasible, affordable, sustainable and safe (“AFASS”), avoid- Transition to Replacement Feeds for Infants Who ance of all breastfeeding by HIV-infected moth- Have Been Exclusively Breastfed ers is recommended’ [4] . Otherwise, exclusive Early cessation of breastfeeding means complete- breastfeeding is recommended during the first ly stopping breastfeeding before age 2 years and, 3 6 months of life. To minimize HIV transmission ideally, among HIV-positive mothers as soon as risk, breastfeeding should be discontinued as replacement feeding is ‘AFASS’. Complementary soon as feasible, taking into account local cir- feeding is necessary for all infants by 6 months of cumstances, the individual woman’s situation age. Guidelines on how to manage the transition and the risks of replacement feeding (including from exclusive breastfeeding to replacement feed- infections other than HIV and malnutrition). Ta- ing are offered in table 4. At 6 months, if replace- ble 1 provides guidance on how this decision may ment feeding is still not ‘AFASS’, continuation of be made. breastfeeding with additional complementary Exclusive breastfeeding means giving a child foods is recommended. Well-chosen comple- no other food or drink, including water, in addi- mentary foods, such as fresh orange juice, pota- tion to breastfeeding with the exception of medi- toes, dark green vegetables and meats, should cines, vitamin drops or syrups and mineral sup- supplement the nutrients that replacement milk plements. Replacement feeding means giving an does not adequately provide. infant who is not receiving any breast milk a nutritionally adequate diet until the age at which the Other Measures child can be fully fed on family foods. WHO/ Adequately heat-treated, expressed milk of HIV- UNAIDS/UNICEF recommend several varia- positive mothers does not transmit HIV and re-

HIV and AIDS 163 Table 1. Considerations for deciding on the most feasible infant feeding option for HIV-positive mothers

Most feasible option

breastfeeding/ unclear replacement feeding or wet-nursing expressed, heat-treated breast milk

Drinking-water River, stream, pond, Public standpipe Piped water at home or ability supply or well to purchase clean water Latrine None or pit latrine VIP latrine Waterborne latrine Income Less than USD 15 USD 15 available for formula most USD 15 available for formula available for months every month (unless using formula each month expressed breast milk) Food storage No refrigerator or Access to refrigerator with Refrigerator at home with regular electricity regular electricity supply, regular electricity supply supply available but not at home Preparation Inability to boil Ability to boil water for every feed Ability to boil water for every and fuel water and utensils but with effort feed for every feed Ability to Preparation of Preparation of replacement feeds Preparation of replacement prepare night replacement feeds at night possible but with effort feeds at night possible feeds at night difficult Family and Breastfeeding Replacement feeding acceptable, Family aware of HIV status and community expected, and but family unaware of HIV status; willing to help with feeding support family unaware or breastfeeding expected, of HIV status but family aware of HIV status and willing to help with feeding

From WHO, UNICEF, UNAIDS, UNFPA [5].

Table 2. WHO/UNAIDS/UNICEF [6] feeding options for infants of HIV-infected mothers

Breast milk Replacement milks

Exclusive breastfeeding by the mother for 6 months and Commercial infant formula, prepared according to continuing until age 2 years, or as long as mother chooses manufacturer’s directions Exclusive breastfeeding by the mother with early cessation, Fresh full cream milk; with added water, sugar, and with rapid weaning to replacement milk as early as feasible micronutrients; boiled before use Breast milk expression with heat treatment; expressed milk Evaporated full cream milk or powdered full cream fed via cup milk; with added water, sugar, and micronutrients Wet-nursing by an HIV-uninfected mother

All feeding options recommend introduction of complementary foods at 6 months of age.

164 Pediatric Nutrition in Practice Table 3. Strategies to minimize the risk of HIV transmis- Table 4. Advice for mothers on how to manage the tran- sion during breastfeeding sition from exclusive breastfeeding to replacement feeding Practice exclusive breastfeeding – ideally for 6 months Allow the infant to adjust to the new feeding pattern Stop breastfeeding as soon as replacement feeding is over a period of 2 days to 2 weeks acceptable, feasible, affordable, sustainable and safe – preferably no later than 6 months Accustom the infant to cup feeding by introducing expressed breast milk by cup. One strategy to help the Good lactation management (early initiation, attach- baby adapt to cup feeding is to offer expressed breast ment, positioning, frequent feeds, learning to express) milk by cup between regular breastfeeds can prevent breastfeeding problems such as cracked nipples, engorgement and mastitis Eliminate one breastfeed at a time once the infant ac- cepts cup feeding and replace with expressed breast When cracked or bleeding nipples, mastitis or abscess- milk given by cup es do develop, continue feeding from the unaffected side, and regularly express milk from the affected side Express breast milk and discard it if the breasts become and discard it engorged during this process. Cold compresses may reduce inflammation due to engorgement Condoms must be used during sexual intercourse throughout the lactation period Avoid reinitiating breastfeeding after completing the transition to replacement feeding. Resist the desire to Oral thrush or mouth ulcers in the infant should be breastfeed at night or when the child wants comfort- promptly treated ing Expressed breast milk can be heat treated; for instance, If it is necessary to offer breast milk after replacement during periods of increased risk of transmission sec- feeds have commenced ensure that the milk is heat- ondary to cracked nipples, or during transition from ex- treated and given by cup clusive breast to replacement feeding

mains nutritionally and immunologically supe- Feeding the HIV-Infected Child rior to infant formula. Methods of heat treatment 3 suitable for domestic use include the Pretoria At their first contact with a healthcare profes- pasteurization and the flash heating methods [7] . sional, all children with HIV should have their Expression and heat treatment can be a tempo- anthropometric status (e.g. weight, height, head rary measure during periods of increased risk of circumference and arm circumference) mea- transmission secondary to cracked nipples, for sured, and should be screened for nutritional instance, as well as during transition from exclu- problems. In addition, a 24-hour recall or diet re- sive breastfeeding to replacement feeding. Wet- cord should be obtained and compared with esti- nursing may be considered in communities where mated needs to assess adequacy of intake. Follow- this option is accepted. The wet-nurse needs to up assessment should be conducted every 1–6 have a negative HIV test before and 6 weeks after months, depending on the child’s age, identified starting. Experience with breast-milk banks in concerns, and nutritional status. Latin America, particularly Brazil and South Af- Nutritional therapy is best given orally. Since rica, has been positive though limited. Heat treat- it is difficult to calculate the precise caloric needs ment of breast milk is recommended for all milk of an HIV-infected child, the energy intakes for banks. HIV-infected children experiencing weight loss need to be increased by 50–100% over established requirements for otherwise healthy uninfected

HIV and AIDS 165 children [8] . The formula volume should be in- ceive periodic (every 4–6 months) vitamin A sup- creased as much as can be tolerated. If the child plements in the same dose as other children. is eating solids, adding a high-fat supplement There are no evidence-based guidelines on the such as oil or margarine may be helpful. Com- appropriate prescription of micronutrient sup- mercial nutritional supplements are an accept- plements for HIV-infected children. able alternative. Enteral supplementation should be considered if the child cannot eat or absorb adequate Highly Active Antiretroviral Therapy calories orally to sustain growth. Nasogastric tube feedings should be tried first, to demon- The initiation of highly active antiretroviral ther- strate the child’s ability to gain weight with sup- apy (HAART) is associated with improvements plemental enteral feedings. Additional nighttime in many growth parameters for HIV-infected feedings are most practical, since they allow the children. Immediate gains first manifest in child to eat normally during the day. Complica- weight and arm muscle circumference. Lean tions include sinusitis and worsening esophageal body mass improves as well, while a height re- candidiasis. Caregivers may be unable or unwill- sponse occurs more slowly. Body mass index does ing to maintain nasogastric feeding. If nasogas- not increase in all children, but improvements tric tube feedings improve growth, placement of are greatest in children with the lowest baseline a more permanent device, such as a gastrostomy body mass index and who have more advanced tube, should be considered. Parenteral nutrition HIV disease. Children are not spared the meta- should be reserved for HIV-infected children bolic effects of HAART, and they too have a sig- who continue to lose weight on an aggressive en- nificant (up to 33%) risk of lipodystrophy. No teral program, or for children who have persis- therapeutic strategies to diminish the clinical tent diarrhea with weight loss or severe recurrent and biochemical features of the fat redistribution or chronic pancreatic or biliary tract disease. syndrome have been described in children. However, central venous catheters pose their own additional risk for sepsis. Conclusions

Micronutrients • Infant feeding should be considered part of a continuum of care and support services for Micronutrient deficiencies are common in HIV- HIV-infected women and children infected adults and children and may accelerate • Decisions about the optimal feeding mode for progression of HIV disease, which in turn leads HIV-exposed infants are difficult and depend to worsened nutritional status [8] . Nutritional in- on parents’ individual choice. However, health terventions might restore intestinal absorption workers can assist this decision-making by and increase CD4 cell numbers. Adequate micro- discussing safety considerations with parents nutrient intake is best achieved through an ade- • A focus on the growth and nutrition of the quate diet. Few randomized trials have examined HIV-infected child at each visit is warranted. the efficacy of direct micronutrient supplementa- An adequate diet, prevention of opportunistic tion of children born to HIV-infected mothers. In infections and HAART all contribute to en- keeping with WHO recommendations, children suring satisfactory growth younger than 5 years born to HIV-infected moth- • There is limited evidence for routine micronu- ers living in resource-limited settings should re- trient supplementation, other than vitamin A

166 Pediatric Nutrition in Practice References

1 Katz A: The evolving art of caring for 4 WHO: New Data on the Prevention of 6 WHO, UNAIDS, UNICEF: HIV and pregnant women with HIV infection. J Mother-to-Child Transmission of HIV Infant Feeding Counselling: A Training

Obstet Gynecol Neonatal Nurs 2003; 32: and Their Policy Implications: Conclu- Course. Geneva, WHO/UNAIDS/ 102–108. sions and Recommendations. WHO UNICEF, 2000. WHO document WHO/ 2 The Breastfeeding and HIV Interna- Technical Consultation on Behalf of the FCH/CAH/00.2–4. tional Transmission Study Group, UNFPA/UNICEF/WHO/UNAIDS 7 Saadeh RJ, Henderson P, Vallenas C: Coutsoudis A, Dabis F, Fawzi W, et al: Inter-Agency Task Team on Mother- Infant Feeding and HIV Transmission. Late postnatal transmission of HIV-1 in to-Child Transmission of HIV. WHO/ Consultation on Nutrition and HIV/ breast-fed children: an individual pa- RHR/01.28 ed. Geneva, WHO, 2001. AIDS in Africa: Evidence, Lessons and tient data meta-analysis. J Infect Dis www.who.int/reproductive-health/pub- Recommendations for Action, Durban,

2004; 189: 2154–2166. lications/new_data_prevention_mtct_ 2005. Geneva, WHO, 2005. 3 Coutsoudis A: Breastfeeding and HIV. hiv/index.html. 8 WHO: Nutrient Requirements for Peo- Best Pract Res Clin Obstet Gynaecol 5 WHO, UNICEF, UNAIDS, UNFPA: ple Living with HIV/AIDS: Report of a

2005; 19: 185–196. HIV and Infant Feeding: A Guide for Technical Consultation. Geneva, WHO, Health-Care Managers and Supervi- 2003. sors. Geneva, WHO, 2003.

HIV and AIDS 167 Koletzko B. (ed): Pediatric Nutrition in Practice. Basel, Karger, 2008, pp 168–170

3 Nutritional Challenges in Special Conditions and Diseases

3.8 Cholestatic Liver Diseases Edmond Rings

Key Words Poor dietary intake is an important factor in Cholestatic liver disease ؒ Fat malabsorption ؒ the pathophysiological basis of malnutrition in Vitamins, fat-soluble children with CLD. Often energy expenditure is increased in these children. Their nutritional status may be further compromised by decreased Key Messages absorption of macronutrients, in particular of fat. R Cholestatic liver disease (CLD) in children nega- The obstruction or absence of bile ducts often ob- tively affects nutritional status, growth and devel- served in CLD leads to accumulation of bile acids opment in hepatocytes, which results in liver damage. As R Poor dietary intake is an important factor in the a result, the enterohepatic circulation of bile acids pathophysiological basis of malnutrition in children with CLD is interrupted. The resulting reduction or absence R For children with CLD, the dietary energy intake is of bile acids in the intestinal lumen leads to im- usually increased to levels of 120–150% of the daily paired micellization and therefore to strongly re- reference intake duced absorption of fats and fat-soluble nutrients R Continuous nasogastric drip-feeding may be need- [2] . At an early age, fat absorption is critical, since ed in infants to guarantee optimal uptake of nutrients fat accounts for the most important dietary en- R A marked reduction of bile acids in the intestinal ergy source (up to 50% of total ingested energy in lumen, as observed in cholestasis, reduces absorp- milk-fed infants). Furthermore, essential fatty tion of fat-soluble vitamins A, D, E and K, and sup- acids (EFAs) and long-chain polyunsaturated fat- plements may be needed ty acids (LCPUFAs) are indispensable for proper Copyright © 2008 S. Karger AG, Basel development and function of different organs. Micronutrient absorption might also be affected in CLD, including absorption of fat-soluble vita- Introduction mins, A, D, E and K.

Cholestatic liver disease (CLD) in children negatively affects nutritional status, growth and de- D i e t a r y I n t a k e velopment, leading to an increased risk of morbidity and mortality [1] . Nutritional strategies to The dietary prevention or treatment of failure to optimize feeding of children with CLD are avail- thrive during CLD involves some general princi- able. Patients with CLD, however, form a hetero- ples applicable to virtually all patients, and some geneous group and the clinical manifestations of individual tailor-made approaches. Poor dietary their disease vary. This makes a tailor-made di- intake is an important factor in the pathophysio- etary approach for these children crucial. logical basis of malnutrition in children with CLD. Reduced gastric volume as a result of or- At an early age, fat accounts for the most im- ganomegaly and ascites, vomiting, and hypogly- portant dietary energy source (up to 50% of total cemia leads to limited absorption of the required ingested energy in infants fed human milk or in- dietary nutrients when administered in regular fant formula). EFAs and LCPUFAs are indispens- (bolus) feedings. Fatigue, anorexia, nausea, diar- able for proper development and function of dif- rhea, altered or reduced ability to taste, and early ferent organs, for example the central nervous satiety may all contribute to decreased ingestion system. In CLD, up to 60% of the fat components, of food. Additionally, many diet modifications, particularly long-chain triglycerides, are substi- for example sodium, fluid or protein restrictions, tuted by medium-chain triglycerides (MCTs), make food even more difficult to eat. These di- whose absorption can occur relatively indepen- etary restrictions are imposed on patients with dent of the presence of bile components in the relatively high risks on fluid overload and enceph- intestinal lumen. Breastfed children receive ad- alopathy which, when left untreated, can lead to ditional formula and MCT-rich oil, while for serious and often irreversible defects [3] . Under older children feeding with formula is often these circumstances, continuous nasogastric drip- prolonged and energy-rich liquids are provided. feeding may be needed to guarantee maximal up- Adequate intake of EFAs and LCPUFAs is not take of nutrients. Apart from reduced intralumi- frequently monitored in CLD patients, but strived nal bile acid concentrations, other consequences for by providing these fatty acids in ample of CLD, such as gastrointestinal bleeding, im- amounts in the diet. Nevertheless, we reported paired digestive enzyme production and secre- that about 70% of children with CLD requiring tion, mucosal congestion, villous atrophy, bacte- liver transplantation have biochemical indica- rial overgrowth or pancreatic insufficiency can tions of EFA and LCPUFA deficiency [5] . lead to maldigestion and malabsorption of nutri- In children with CLD, carbohydrate homeo- ents. In addition, even certain medications can stasis can be affected by hepatic failure itself, for aggravate malabsorption. For example, cholestyr- example by decreased capacity of gluconeogene- amine binds to bile acids in the intestinal lumen sis. Frequently, also peripheral utilization of glu- 3 and thereby further reduces absorption of fat-sol- cose is reduced, which may decrease the risks of uble nutrients. Also, the reduced availability of hypoglycemia. In CLD, hepatic degradation of specific nutrients involved in digestion and/or ab- insulin may also be decreased, which may be one sorption of other nutrients, specifically vitamins of the causes for the twofold higher insulin re- and minerals, affects intestinal absorption [3] . sponse in CLD compared to control patients. El- evated plasma levels of insulin in combination with glucose tolerance imply insulin resistance, Macronutrients which could be further aggravated by increased circulating free fatty acids as seen in CLD [3] . The In CLD, the nutritional status may be further carbohydrate content can be increased by supple- compromised by decreased absorption of macro- mentation of formula with maltodextrin. nutrients, including fat, carbohydrates and pro- Addition of proteins and especially specific teins [4] . For children with CLD, the dietary en- amino acids such as branched chain amino acids ergy intake is usually increased to levels of 120– could improve the nutritional status of children 150% of the dietary reference intake of energy for with CLD [6] . However, care must be taken be- age and gender. The adaptation of the diet in- cause an excess of protein can negatively influ- volves the increment of the concentration and ence encephalopathy. amount ingested.

Cholestatic Liver Diseases 169 Table 1. Oral supplementation of fat-soluble vitamins in duce zinc deficiency. Zinc deficiency has a negative infants with chronic cholestasis [7] impact on cognitive function, appetite and taste, Vitamin Regimen immune function, wound healing and protein metabolism. In addition, zinc deficiency has frequent- A Water-soluble preparation ly been associated with essential fatty acid defi- 5,000–25,000 units/day ciency [8] . Finally, uptake of selenium can be dis- D Vitamin D, 800–5,000 units/day, or turbed due to essential fatty acid deficiency, and ␮ 25-hydroxyvitamin D3, 3–5 g/kg/day iron depletion is seen as a result of gastrointestinal E D-␣-Tocopherol-polyethylene glycol-1000 bleeding, insufficient uptake, transport and han- succinate (TPGS), 15–25 IU/kg/day, or dling of iron. In addition, liver dysfunction strong- ␣-tocopherol, 25–200 IU/kg/day ly reduces storage capacity of vitamins such as fo- K 2.5 mg twice per week late, riboflavin, nicotinamide, pantothenic acid, pyroxidine, vitamin B12 , thiamine and vitamin A. Hepatocellular injury in CLD also results in defects in vitamin activation, conversion, release and Micronutrients transport [3] . Addition of zinc to the diet could counteract a part of the poor dietary intake. The absence of bile acids in the intestinal lumen as observed in cholestasis reduces absorption of fat- soluble vitamins A, D, E and K. Adequate absorp- Conclusions tion of fat-soluble vitamins during CLD can usually be obtained by profoundly increasing the • Nutritional strategies are available to opti- daily-administered dosages, well above regular mize feeding of children with cholestatic liver recommendations for the age groups ( table 1 ) [7] . disease (CLD) Serum levels of fat-soluble vitamins are regularly • In CLD, the nutritional status may be compro- monitored in order to adapt dosages. Calcium up- mised by decreased absorption of macronutri- take is at risk as a result of the formation of non- ents, including fat, carbohydrates and proteins soluble calcium-fatty acid soaps during fat malab- • Adequate absorption of fat-soluble vitamins dur- sorption. Hypovitaminosis D may increase renal ing CLD can usually be obtained by profoundly loss of phosphate, and hypovitaminosis A may in- increasing the daily-administered dosages

References

1 Barshes NR, Lee TC, Udell IW, et al: 3 Matos C, Porayko MK, Francisco-Ziller 6 Mager DR, Wykes LJ, Roberts EA, et al: The pediatric end-stage liver disease N, DiCecco S: Nutrition and chronic Branched-chain amino acid needs in

(PELD) model as a predictor of survival liver disease. J Clin Gastroenterol 2002; children with mild-to-moderate chron-

benefit and posttransplant survival in 35: 391–397. ic cholestatic liver disease. J Nutr 2006;

pediatric liver transplant recipients. 4 Mattar RH, Azevedo RA, Speridião PG, 136: 133–139.

Liver Transpl 2006; 12: 475–480. et al: Nutritional status and intestinal 7 Kelly DA: Diseases of the Liver and Bil- 2 Rings EH, Minich DM, Vonk RJ, et al: iron absorption in children with chron- iary System in Children, ed 2. Oxford, Functional development of fat absorp- ic hepatic disease with and without Blackwell, 2004, p 62. tion in term and preterm neonates cholestasis (in Portuguese). J Pediatr 8 Chin SE, Shepherd RW, Thomas BJ, et

strongly correlates with ability to ab- (Rio J) 2005; 81: 317–324. al: The nature of malnutrition in chil- sorb long-chain fatty acids from intesti- 5 Sealy MJ, Muskiet FAJ, Boersma ER, et dren with end-stage liver disease await-

nal lumen. Pediatr Res 2002; 51: 57–63. al: Essential fatty acid deficiency in ing orthotopic liver transplantation.

pediatric patients. Tijdschr Kinderge- Am J Clin Nutr 1992; 56: 164–168.

neeskd 1997; 65: 144–150.

170 Pediatric Nutrition in Practice Koletzko B. (ed): Pediatric Nutrition in Practice. Basel, Karger, 2008, pp 171–177

3 Nutritional Challenges in Special Conditions and Diseases

3.9 Malabsorptive Disorders and Short Bowel Syndrome Olivier Goulet

Key Words Introduction ؒ Short bowel syndrome ؒ Intestinal adaptation ’Protracted diarrhea of infancy ؒ Parenteral The so-called ‘protracted diarrhea of infancy -nutrition ؒ Oral feeding ؒ Enteral feeding ؒ Breast (PDI), which has become a rare condition in de -milk ؒ Long-chain fat-containing formulas ؒ veloped countries, is caused by severe malabsorp Medium-chain triglycerides ؒ Hydrolyzed protein tion secondary to an acquired intestinal mucosa formulas ؒ Amino acid formulas ؒ Small intestinal injury due to infection, inflammation or allergic bacterial overgrowth ؒ Feeding aversion reaction. ‘Intractable diarrhea of infancy’ refers to congenital enteropathies involving the development or renewal of intestinal mucosa that lead Key Messages to very long lasting or often irreversible intestinal R Protracted diarrhea of infancy or short bowel syn- failure [1] . Short bowel syndrome (SBS) is a state drome require parenteral nutrition together with of malabsorption following extensive small intes- oral feeding or enteral feeding. The use of the gastrointestinal tract as early and as much as possible, tinal resection. The functional consequences as according to clinical tolerance, should be promot- well as the prognosis of SBS depend on the age- ed and feeding aversion prevented adjusted small bowel length, site of resection and 3 R Adaptation – the physical and physiological pro- occurrence of cholestasis [2] . The cause of resec- cesses by which the intestine compensates for loss tion and age of the patient also influence the of intestinal length or function – is optimized with functional capacity of the remnant gut and its po- the provision of oral feeding or enteral feeding R Direct contact with nutrients, pancreaticobiliary tential for adaptation [2, 3] . By maintaining an secretions, and neurohormonal factors explain optimal nutritional status during the long period how the use of the gastrointestinal tract promotes required for adaptation of the remnant small in- adaptation. It may also contribute to prevent cho- testine, parenteral nutrition (PN) is the corner lestasis and liver disease stone of management, but as much oral or enteral R Intestinal microflora has both positive (short-chain fatty acid production) and deleterious effects (in- feeding as possible should be provided to the pa- traluminal bacterial overgrowth) and may be mod- tient via the intestine in order to improve the ulated in short bowel syndrome patients physiological processes of short bowel adapta- R Composition of dietary intake regarding breast tion. Moreover, in infants or children oral feed- milk, amino acid- and long-chain fat-containing ing skills have to be acquired or maintained. Dif- formulas remain controversial. Very few random- ferent concepts exist with respect to what the ized trials have been performed. The routes (oral, gastric, trans-pyloric) and the modes (bolus, con- composition of feeding (elemental, semi-elemen- tinuous, both) of feeding are also debated tal or polymeric) and the mode of delivery (oral Copyright © 2008 S. Karger AG, Basel feeding or gastric tube feeding) should be. Cur- rent studies do not provide evidence-based data use [7] . Breast milk should be used as often as for establishing recommendations for SBS pa- possible in patients with neonatal SBS by breast- tients. Patients suffering disease involving the in- feeding or tube feeding. testinal mucosa or gut motility also require pro- The choice of enteral formula is controversial. tracted periods of PN. A limited mucosal absorptive surface area can lead to lactose, long-chain fatty acid and protein malabsorption. In PDI, electrolyte and metabolic Rationale for Enteral Feeding balance can be difficult to achieve. In SBS patients, complex nutrients may promote mucosal The use of the gastrointestinal tract is vital for cell proliferation via direct contact with disac- preserving or restoring normal intestinal struc- charides [8] . Additionally, colonic exposure to lu- ture and function [3] . Functional intestinal adap- minal nutrients promotes release of trophic fac- tation refers to the gross anatomic and histologic tors that enhance small bowel mucosa trophi- changes that occur after extensive intestinal re- city. section. Following bowel enlargement and villi Oligo- and polysaccharides are poorly tolerat- lengthening, the intestinal absorptive surface ed by patients, being broken down by osmotical- area increases, and absorptive function gradually ly active organic acids that can present a major improves. Changes in intestinal motility, com- osmotic load to the distal small intestine and co- mensal microbiota, and barrier function are as- lon. In patients with intractable diarrhea of in- sociated with the anatomic and histologic chang- fancy, carbohydrate content should not exceed es. The use of the intestinal tract plays a critical 40% of calories and be lactose-free. role in the process of intestinal adaptation, based Fiber supplementation, by promoting the pro- on the effects of direct nutrient contact with the duction of short-chain fatty acids, such as butyr- mucosa, pancreatic and hepatobiliary secretions, ate, have trophic effects on the small intestine. and the release of circulating hormones. In pa- Long-chain triglycerides are poorly absorbed tients with PDI or SBS, only a few clinical trials in patients with reduced absorptive surface. In have been performed, but they support that case of small intestine bacterial overgrowth, bac- enteral feeding maintains and/or promotes in- teria metabolize and inactivate bile acids, pre- testinal function [4–6] . The choice of the diet as venting the solubilization necessary for long- well as the mode of delivery remains debated (ta- chain triglyceride digestion. bles 1, 2 ). Medium-chain triglycerides (MCTs) are rapidly hydrolyzed by pancreatic lipase and are less dependent on an extensive absorptive surface for Which Diet Is to Be Used adequate absorption. They are water-soluble and can be absorbed intact, directly into the portal Breast milk contains lactose and is considered to circulation [9] . Excessive intake of MCTs can be not well tolerated in patients with reduced in- cause diarrhea and ketosis, while MCTs do not testinal surface area. Breast milk contains many provide essential fatty acids. Current clinical factors that may promote intestinal adaptation practice is based on formulas containing no more and was shown to improve immune function, as than 60% MCTs as fat. well as the genesis of a fecal microflora rich in Whether the molecular form of the nitrogen in- lactobacilli and bifidobacteria. In infants with take might influence PN duration and/or the oc- SBS, the percentage of days that infants received currence of non-IgE-mediated sensitization and breast milk was correlated with fewer days of PN allergic enteritis remains debated. The link be-

172 Pediatric Nutrition in Practice Table 1. Which type of diet should be used Table 2. Management and outcome of neonatal short bowel syndrome (SBS) according to anatomical charac- Breast milk teristics – Contains lactose, growth factors, nucleotides, long-chain fatty acids, glutamine, and other amino acids that promote SBS is a very variable condition which can be as mild as that intestinal adaptation following terminal ileal resection to a very debilitating condi- – Promotes microbiota rich in lactobacilli and bifidobacteria tion which follows total jejuno-ileal and colonic resection. – In infants with SBS, it reduces the duration of parenteral nu- Management and outcome vary according to the cause, the trition extent and site of resection, and the degree of adaptation of – Should be used as much as possible in neonatal SBS by the remaining bowel. Patients with dilated, poorly motile seg- breastfeeding or tube feeding ments of small bowel (gastroschisis, atresia, necrotizing enterocolitis) could benefit from an approach aiming to reduce Enteral formulas bowel dilatation and small intestinal bacterial overgrowth Carbohydrates (SIBO), since they may rapidly develop severe liver disease. Oligo- and polysaccharides Adapted parenteral nutrition (PN), delivered as soon as toler- – Poorly tolerated by patients with limited mucosal absorp- ance permits by cyclical infusion, is mandatory. Early oral feed- tive surface area ing (OF) should be promoted while the benefits of continuous – Broken down into small intestinal lumen in osmotically ac- enteral feeding (CEF) should be balanced in combination with tive organic acids PN; the risk of ‘intestinal overload’ with subsequent SIBO and – Should not exceed 40% of calories, and be lactose-free in tube feeding induce food aversion and eating disorders patients with intractable diarrhea of infancy Fiber supplementation – SBS with small bowel length (SBL) of <40 cm with loss of the – Helpful in older children with SBS with intact colon ileocecal valve (ICV) and associated partial or large colectomy: – Promotes colonic bacterial production of short-chain fatty Patients need very long-term home PN, often indefinite. acids The indication to reduce PN is weight gain beyond the de- Lipids sired limit and the fact that a reduced rate of infusion does Long-chain triglycerides not cause electrolyte imbalance and dehydration. Patients – Poorly digested in case of small intestine bacterial over- with total colectomy or permanent proximal jejunostomy growth because of bile acid changes will remain indefinitely dependent on PN – Poorly absorbed in patients with severe malabsorption – SBS with SBL of <40 cm or only duodenum with totally or – Have trophic effects on small intestinal mucosa largely intact colon: Patients need long-term home PN. – Supplementation with n-3- or n-6-polyunsaturated fatty However, many infants and children may have a degree of acids may enhance mucosal growth adaptation and require less PN and benefit from orally and/ Medium-chain triglycerides (MCTs) or enterally administered nutrients. Some of them may be – Rapidly hydrolyzed by pancreatic lipase progressively weaned from PN. Infants with duodeno-right – Do not provide essential fatty acids colon anastomosis have no chance of being weaned from 3 – Less dependent on an extensive absorptive surface for ad- PN and should not receive CEF instead of oral feeding to equate absorption protect the liver and promote optimal psychological be- – Water-soluble and absorbed intact, directly into the portal havior. These patients are at the highest risk of developing circulation D-lactic acidosis – As part of lipid supply appropriate for most infants with SBS – SBS with SBL of 40–100 cm with loss of the ICV and associated – Excessive intake can cause diarrhea partial or large colectomy: Patients require mid-term home – Recommended use of formulas containing no more than PN and can immediately be fed orally. Adapted CEF com- 60% MCTs as fat bined with oral feeding may help to reduce the PN duration. Bile salt-induced diarrhea may impede rapid PN wean- Nitrogen ing Hydrolyzed protein formulas – Used for many years – SBS with SBL of 40–100 cm with terminal ileum and the entire – Have changed the incidence and outcome of protracted colon: Patients require very short-term PN and can immedi- diarrhea of infancy ately be fed orally. Adapted CEF in combination with oral – No demonstrated advantages in comparison with intact feeding may help to significantly reduce PN duration protein infant formula – Lactose-free and contain MCTs – SBS with terminal ileum resection: Patients have a bile salt- – Largely used and recommended in SBS patients induced diarrhea, and benefit from the administration of Elemental amino acid-based formula 1–2 g of cholestyramine 3 times a day to bind bile salts left – Not yet established whether this type of formula can influ- unabsorbed by the resected ileum. Vitamin B12 plasma lev- ence the outcome of SBS els should be measured and if low, supplemental B12 should Glutamine (Gln) be provided by intramuscular injection at a dose of 100– – Currently no benefit demonstrated 150 ␮g orally or 1,000 ␮g every 6 months

Malabsorptive Disorders and Short Bowel Syndrome 173 Table 3. Small intestine bacterial overgrowth (SIBO) tween small intestine bacterial overgrowth, abnormal mucosal permeability and associated – Several factors intrinsic to short bowel syndrome (SBS) predispose to SIBO and explain its high prevalence in this patient protein sensitization is possible, but the relevance population of elemental diets has also not been clinically es- – Poorly motile segments of the short bowel in close proximity to the colon are common in patients with SBS and dysmotili- tablished (table 3). Only very few clinical trials ty, and the stagnation and contamination that results pro- involving elemental formulas are currently avail- mote abnormal growth of bacteria in the small intestine – SIBO may significantly compromise the digestive and ab- able to establish recommendations. Patients with sorptive functions and may delay or prevent weaning from dilated, poorly motile segments of small bowel parenteral nutrition should benefit first from an approach aiming to – Traditional clinical tests for overgrowth may be unreliable – Management may include surgery if advocated. Antibiotic reduce bowel dilatation and small intestine bac- therapy should vary according to the risk of selecting highly terial overgrowth, since these patients may de- resistant bacterial strains – Intestinal microbiota play an important role in intestinal ad- velop severe liver disease [10] . aptation and should be preserved as much as possible Hydrolyzed protein formulas (HPFs) have been – The use of probiotics offers potential based on experimental evidence, but there is a lack of sufficient data from human used for many years and have changed the inci- studies dence and outcome of PDI during the last de- – D-Lactic acidosis is secondary to bacterial hypermetabolism, especially in the colon, as a consequence of intestinal malab- cades. HPFs have been evaluated by comparison sorption with intact protein infant formula in a crossover Definition study of 60 days duration in 10 infants with SBS Colony-forming units (CFUs) per milliliter of bacteria in the proxi- [11] . No effect of formula type was observed on mal small bowel – Overgrowth of >105 CFUs/ml growth, nitrogen absorption, or mucosal perme- – Overgrowth of >103 CFUs/ml provided that the species of ability. In general, HPFs are lactose-free and con- bacteria isolated from the jejunal aspirate are those that normally colonize the large bowel or provided that those same tain MCTs [11, 12] . species are absent from the saliva and gastric juice Elemental amino acid-based formulas (EA- – Breath hydrogen testing ABFs) have been introduced more recently for Caused by small intestine stasis from: infants suffering from severe allergic diseases. It – Intestinal obstruction (e.g. stenosis, narrowed anastomosis) – Blind loop from termino-lateral anastomosis is not yet established if this type of formula can – Dilated and poorly motile segments of small bowel in close influence the outcome of SBS. The beneficial ef- proximity to the colon fects of EAABFs were reported in an open trial – Contamination from inappropriate enteral feeding involving only 4 SBS patients with persistent Consequences feeding intolerance [7] . A retrospective study – Small intestine mucosal injury with villous atrophy and subsequent malabsorption found a shorter duration of PN dependency with – Increased small intestine mucosal permeability the use of EAABFs [13] . Current data are not yet – IgE-mediated sensitization and allergic enteritis – Gram-negative sepsis from bacterial translocation sufficient to recommend such expansive formu- – Cholestasis and end-stage liver disease (cirrhosis) las for infants and children with SBS. Management Glutamine (Gln), a nonessential amino acid, – Reversal or removal of any predisposing condition(s) plays an important role in energy metabolism of – Redo-anastomosis – Enteroplasty the intestinal mucosa and other rapid turnover R Small intestinal tapering and lengthening tissues. A randomized controlled pilot study of (Bianchi procedure) R Serial transverse enteroplasty (STEP procedure) Gln-supplemented enteral feeding in infants with – Appropriate nutritional support/replacement intestinal failure failed to show any advantages – Suppression or eradication of the contaminating bacterial [14] . Gln cannot be recommended unless larger flora R Intermittent bowel decontamination with antibiotics multicenter trials in infants with intestinal fail- R Use of probiotics ure can provide evidence. (Lactobacillus GG, Saccharomyces boulardii, etc.)

174 Pediatric Nutrition in Practice Table 4. Different routes of feeding

Devices Indications Contraindications Advantages Disadvantages or risks

Oral feeding None To be used Artificial ventilation Discontinuous physiologic Insufficient intake systematically Oro-facial malformation mode of feeding Self-regulation of intake EGF release by salivary glands Promote bowel adaptation Psychological behavior

Gastric feeding Nasogastric Nutritional support Severe GE reflux, Easy to place even at home Frequent dislodgements <3 months Slow gastric emptying Nasal symptoms

Percutaneous Nutritional support Repeated abdominal Fewer occlusions with larger Skin injury at abdominal exit site endoscopic >3 months surgery bore, one-step low-profile gastrostomy Abnormal gastric devices available anatomy

Surgical Nutritional support Poor candidate for Immediate placement of Open surgery gastrostomy >3 months surgery low-profile device, direct visualization of stomach

Duodenal or jejunal feeding Nasojejunal Short term for Recent proximal surgical Radiologic or bedside Frequent dislodgements patients with severe anastomosis placement techniques, Risk of intussusception GERD, gastric noninvasive Nasal symptoms dysmotility Intestinal contamination

Gastrojejunal Longer-term EF for Recent proximal surgical Endoscopic or radiologic Requires healing of gastrostomy patients with severe anastomosis placement, through existing tract prior to placement GERD, gastric dys- gastrostomy tube Skin injury at abdominal exit site motility or need for Frequent occlusions of jejunal port gastric decompression Intestinal contamination Jejunal Long-term EF for Dysmotility Direct surgical access to Open surgical procedure 3 patients with severe small intestine Mechanical problems GERD, upper intestinal Intestinal contamination dysmotility

EGF = Epidermal growth factor; GE = gastroesophageal; GERD = gastroesophageal reflux disease; EF = enteral feeding.

Water electrolyte losses from persistent diar- to fat-soluble vitamin and vitamin B12 deficiency rhea or end-jejunostomies should be replaced par- requiring monitoring and (parenteral) supple- enterally, based on the electrolyte concentration mentation. of the lost fluids. Monitoring the urine sodium concentration provides guidance for correcting or preventing Na depletion ( ! 10 mEq/l), even if Advancement of Feeding serum sodium is near normal. Magnesium and trace element losses can occur with high stoma Whatever the route of feeding (table 4), enteral output. Zinc supplements are often used empiri- feeding advancement can occur as long as fluid cally, given that serum values do not reliably re- and electrolyte balance is maintained and nutri- flect body stores. Ileal resection or diversion lead tional goals achieved (table 5). Enteral feeding

Malabsorptive Disorders and Short Bowel Syndrome 175 Table 5. Modes and management of feeding may eventually be transitioned to oral/bolus

– Oral feeding (OF) is the most physiological and the most stim- feedings, or oral/bolus and nocturnal feedings to ulating for intestinal adaptation allow more freedom from the feeding pump. The – Continuous enteral feeding (CEF) is beneficial in patients with transition from intestinal failure to adequate in- SBS or IDI, by improving saturation of carrier transport proteins, thus taking full advantage of the available absorptive testinal function can take weeks, months, and surface area as compared to intermittent feeding sometimes years. The infant with SBS improves – Oro-pharyngeal shunting suppresses the direct stimulation of salivary glands resulting in lower release of EGF that is an im- bowel function over time due to the opportunity portant intestinal mucosa trophic factor for further intestinal growth. Provision of oral – Continuous infusion leads to the loss of self-regulation of intake with vomiting or intestinal stasis with increased risk of feeding plays a major role in the management of SIBO with subsequent sepsis, liver injury, etc. any child with intestinal failure, even for those – In case of full EF, small quantities of OF should be introduced in infants 2 or 3 times a day to stimulate sucking and swallow- in whom complete weaning from PN seems un- ing and to minimize the chances of eating disorders in the likely. future – Nasogastric tube may impair normal acquisition of oral behavior and induces eating disorders – Percutaneous gastrostomy is indicated for children who will Conclusions require EF for >3 months – Jejunal feeding R whatever the device (nasojejunal, gastrojejunal, jejunal), • Intestinal adaptation following resection is a it should be limited to very special situations R Exposes to the risk of contaminating the intestine with sub- physiological process best enhanced by the sequent SIBO and sepsis early use of the gastrointestinal tract, espe- R Excessive infusion rate may be responsible for severe diarrhea and dehydration cially by oral feeding • Continuous enteral feeding has advantages for Progression and monitoring of feeding program Intestinal transit must be well established by colo-anal transit or digestion/absorption of nutrients but should ostomy be used carefully to avoid ‘intestinal overload’ Absence of contraindications – Patient’s general condition (sepsis, bleeding, respiratory dis- of poorly motile segments of the short bowel tress syndrome, etc.) and development of eating disorders – Bloody stools – High ostomy or stool output, >3 ml/kg per h ostomy output • Breastfeeding may be used, and may be com- – Bilious and/or persistent vomiting plemented with hydrolyzed protein formulas – Electrolyte instability Quantify feeding tolerance containing up to 60% medium-chain triglyc- – Stool or ostomy output erides. Current data are not sufficient for rec- – Reducing substances in stools or ostomy output ommending elemental amino acid-based for- – Recurrent vomiting and abdominal distension Ultimate goals mula for infants and children with short bow- – Provide 150–200 ml/kg per day, 100–140 kcal/kg per day el syndrome – If ostomy/stool output precludes advancement at 20 cal/oz for 7 days • Small intestinal bacterial overgrowth may sig- – Increasing caloric density of the formula can be performed nificantly compromise digestive and absorp- – Isocaloric reductions in PN support simultaneously with feeding advancement tive functions and may delay or prevent wean- Warning ing from total parenteral nutrition – EF can induce severe adverse effects related to intestinal overload and/or bacterial contamination with subsequent SIBO – A meticulous approach, avoidance of excessive enteral formula supply, strict hygiene measures – Concomitant oral feeding prevents psychological disorders and eating aversion

SBS = Small bowel syndrome; IDI = intractable diarrhea of infancy; EGF = epidermal growth factor; SIBO = small intestine bacterial overgrowth; EF = enteral feeding; PN = parenteral nutrition.

176 Pediatric Nutrition in Practice References

1 Goulet O, Ruemmele F: Causes and 5 Orenstein SR: Enteral versus parenteral 11 Ksiazyk J, Piena M, Kierkus J, Lysz- management of intestinal failure in therapy for intractable diarrhea of in- kowska M: Hydrolyzed versus nonhy-

children. Gastroenterology 2006; fancy: a prospective, randomized trial. drolyzed protein diet in short bowel

130(suppl 1):S16–S28. J Pediatr 1986; 109: 277–286. syndrome in children. J Pediatr Gastro-

2 Goulet O, Sauvat F: Short bowel syn- 6 Sondheimer JM, Cadnapaphornchai M, enterol Nutr 2002; 35: 615–618. drome and intestinal transplantation Sontag M, Zerbe GO: Predicting the 12 Bines J, Francis D, Hill D: Reducing in children. Curr Opin Clin Nutr Metab duration of dependence on parenteral parenteral requirement in children

Care 2006; 9: 304–313. nutrition after neonatal intestinal re- with short bowel syndrome: impact of

3 American Gastroenterological Associa- section. J Pediatr 1998; 132: 80–84. an amino acid-based complete infant tion: American Gastroenterological 7 Andorsky DJ, Lund DP, Lillehei CW, et formula. J Pediatr Gastroenterol Nutr

Association medical position state- al: Nutritional and other postoperative 1998; 26: 123–128. ment: short bowel syndrome and intes- management of neonates with short 13 Vanderhoof JA, Young RJ: Hydrolyzed tinal transplantation. Gastroenterology bowel syndrome correlates with clini- versus nonhydrolyzed protein diet in

2003; 124: 1105–1110. cal outcomes. J Pediatr 2001; 139: 27–33. short bowel syndrome in children. J

4 Greene HL, McCabe DR, Merenstein 8 Bines JE, Taylor RG, Justice F, et al: In- Pediatr Gastroenterol Nutr 2004; 38: GB: Protracted diarrhea and malnutri- fluence of diet complexity on intestinal 107. tion in infancy: changes in intestinal adaptation following massive small 14 Duggan C, Stark AR, Auestad N, et al: morphology and disaccharidase activi- bowel resection in a preclinical model. Glutamine supplementation in infants

ties during treatment with total intra- J Gastroenterol Hepatol 2002; 17: 1170– with gastrointestinal disease: a ran- venous nutrition or oral elemental 1179. domized, placebo-controlled pilot trial.

diets. J Pediatr 1975; 87: 695–704. 9 Bach AC, Babayan VK: Medium-chain Nutrition 2004; 20: 752–756. triglycerides: an update. Am J Clin

Nutr 1982; 36: 950–962. 10 Quigley EM, Quera R: Small intestinal bacterial overgrowth: roles of antibiotics, prebiotics, and probiotics. Gastro-

enterology 2006; 130(suppl 1):S78–S90.

Malabsorptive Disorders and Short Bowel Syndrome 177 Koletzko B. (ed): Pediatric Nutrition in Practice. Basel, Karger, 2008, pp 178–183

3 Nutritional Challenges in Special Conditions and Diseases

3.10 Celiac Disease Stefano Guandalini

Key Words when assessed, has been reported at similarly Celiac ؒ Gluten high values. In the Saharawi population, CD has been found in as many as 5% of the general population [2] . It must be emphasized that not all those Key Messages affected by CD (children and adults alike) are R Celiac disease is frequent, with a prevalence of symptomatic, and that even symptomatic pa- about 1% tients may present diverse problems, not every- R Non-gastrointestinal manifestations are increas- one showing the classic presentation with gastro- ingly common intestinal complaints. However, diagnosing CD R An effective screening with transglutaminase titers in all affected individuals is imperative, as the is available R The gluten-free diet effectively induces full and condition can be fully reverted to normal with a permanent remission timely institution of a gluten-free diet (GFD), R New data show the possibility of prevention thus preventing the many complications that Copyright © 2008 S. Karger AG, Basel have been described in untreated patients and that eventually may lead to a shorter life expectancy. Introduction

Celiac disease (CD) is an autoimmune disorder Pathophysiology occurring in genetically susceptible individuals, and triggered by the ingestion of a well-identified A clear genetic predisposition exists, as CD only autoantigen (gluten). It affects primarily the occurs in individuals who are either positive for small intestine, where it progressively leads to the haplotype HLA-DQ2 or DQ8. An autoim- flattening of the small intestinal mucosa. Three mune component is present, as demonstrated by cereals contain gluten and are toxic for celiac pa- specific serology for antibodies to the enzyme tis- tients: wheat, rye, and barley. Screening studies sue transglutaminase (TGA). have shown that CD has a very high prevalence, Both the adaptive and the innate immune sys- occurring in about 1% of the general population tems are involved in the cascade of events leading throughout Europe and North America [1] . In to intestinal damage. The adaptive immune re- Latin America, North Africa, the Near and Mid- sponse to gluten has been well elucidated with the dle East and Northwest India, CD’s prevalence, identification of specific peptide sequences able to bind specifically to HLA-DQ2 or DQ8 mole- Table 1. Presentations of celiac disease cules and to then stimulate gluten-specific CD4 Typical Predominant gastrointestinal signs/ T cells. symptoms As for the innate immunity, the intraepithelial – Diarrhea CD8+ T-lymphocytes play an important role in – Vomiting the destruction of epithelial cells. – Failure to thrive CD is a chronic inflammatory disorder lead- – Anorexia – Recurrent abdominal pain ing, if untreated, to the destruction of the small – Constipation intestinal villi, with consequent malabsorption Atypical Gastrointestinal signs/symptoms are of nutrients and minerals. The lesions occur in or extra- minimal or absent. Most common signs/ the proximal small intestine with typical histo- intestinal symptoms of extra-intestinal celiac disease logical changes of villous atrophy, crypt hyper- are reported in table 2 plasia and increased intraepithelial lymphocyto- Silent No signs/symptoms. Gluten-dependent sis. Such damage follows a progressive course, duodenal mucosa changes are typical of and specific histological stages have been de- celiac disease scribed that can be classified [3] as follows: Latent No signs/symptoms. Duodenal mucosa • Type 0 or pre-infiltrative stage (normal) normal. Gluten-dependent changes with • Type 1 or infiltrative lesion (increased in- or without symptoms appear later in time traepithelial lymphocytes) • Type 2 or hyperplastic lesion (type 1 + hyperplastic crypts) • Type 3 or destructive lesion (type 2 + villous atrophy of progressively more severe degrees, ‘Typical’ Celiac Disease: Gastrointestinal denominated 3a, 3b and 3c) Manifestations

The so-called ‘typical’ form of CD presents Clinical Presentation characteristically between 6 and 24 months of 3 age. Symptoms begin at various times after the Four possible presentations of CD are recognized introduction of weaning foods containing glu- [4] (table 1): ten. Infants and young children typically pres- Typical: Characterized mostly by gastrointes- ent with chronic diarrhea, anorexia, vomiting, tinal signs and symptoms. abdominal distension, abdominal pain and poor Atypical or extra-intestinal: Gastrointestinal weight gain or weight loss. Malnutrition can be signs/symptoms are minimal or absent. Various severe if the diagnosis is delayed. Behavioral extra-intestinal manifestations are present. changes are common and include irritability Silent: The small intestinal mucosa is dam- and a sad mood. Older children with CD present aged and CD autoimmunity can be detected by with gastroin testinal manifestations, but symp- serology, but there are no symptoms. toms typically are less evident and include nau- Latent: Asymptomatic, and with normal mu- sea, bloating, abdominal pain, constipation and cosa morphology. These individuals have genetic intermittent diarrhea. The variability in the age compatibility with CD and may also show posi- at onset of symptoms is possibly dependent on tive autoimmune serology. Full-blown CD may the amount of gluten in the diet and other envi- ensue at a later time. ronmental factors such as duration of breastfeeding.

Celiac Disease 179 ‘Atypical’ Celiac Disease: Extra-Intestinal Table 2. ‘Extra-intestinal’ celiac disease Manifestations Dermatitis herpetiformis Permanent enamel hypoplasia More and more patients are being diagnosed Iron-deficient anemia resistant to oral iron supplements without typical gastrointestinal manifestations, Short stature, delayed puberty and at an older age. It is currently estimated that Chronic hepatitis with hypertransaminasemia about half of the patients with newly diagnosed Arthritis Osteopenia/Osteoporosis CD in fact do not present with gastrointestinal Epilepsy with occipital calcifications symptoms. In infants and toddlers, gastrointesti- Primary ataxia, white-matter focal lesions nal symptoms and failure to thrive clearly pre- Psychiatric disorders dominate, while during childhood minor gastrointestinal symptoms, inadequate rate of weight and height gain, and delayed puberty tend to be more common. diagnosis of CD have a low bone mineral den- Table 2 reports the main extra-intestinal man- sity of various severity. Bone mineral density ifestations of celiac disease, briefly summarized improves on GFD, and in children may return below. to normal in as little as 1 year after starting the • Dermatitis herpetiformis: A blistering skin diet rash involving elbows, knees, and buttocks as- • Neurological problems: CD may cause occipi- sociated with dermal granular immunoglobu- tal calcifications and intractable epilepsy. The lin A (IgA) deposits. Rash as well as mucosal association with cerebellar ataxia is well de- morphology improves on a GFD scribed in adults, and other lesions involving • Dental enamel hypoplasia: Only involves the the white matter have also been described permanent dentition and may be the only presenting manifestation of CD • Iron-deficiency anemia: Possibly the most Associated Diseases common manifestation of CD in adults • Short stature and delayed puberty: as many as CD is associated with a number of other disor- 10% of children with ‘idiopathic’ short stature ders: several autoimmune conditions and a few may have CD in the absence of any sign of nu- genetic syndromes, the most common of which tritional deficiencies. Adolescent girls may are listed in table 3 . have delayed menarche • Type-1 (insulin-dependent) diabetes (IDDM): • Chronic hepatitis, hypertransaminasemia: As Approximately 8% of patients with IDDM many as 9% of patients with elevated trans- have increased levels of TGA and show typical aminase levels of unclear etiology may have features of CD on duodenal biopsy. The ap- silent celiac disease. Liver enzymes normalize pearance of CD serology may occur at any on GFD time after the diagnosis of IDDM, thus high- • Arthritis, arthralgias: Arthritis can be a com- lighting the need for repeated testing. Most mon extra-intestinal manifestation of adults commonly, patients with IDDM and CD have with CD including those on GFD. Up to 3% of no or only mild gastrointestinal symptoms. children with juvenile chronic arthritis may As some of these symptoms are also seen in have CD [5] patients with diabetes (e.g. bloating or diar- • Osteopenia/Osteoporosis: Approximately 50% rhea), diagnosis of CD may be missed, unless of children and 75% of adults at the time of a screening is performed. Although there is no

180 Pediatric Nutrition in Practice Table 3. Disorders associated with celiac disease (‘at-risk’ groups to be Condition Average prevalence screened) of celiac disease % Insulin-dependent diabetes mellitus 8 Thyroiditis 5 Sjögren syndrome and other connective tissue diseases 4 Down syndrome 12 Williams syndrome 5 Turner syndrome 5 First-degree relatives of celiac patients 8–10

convincing evidence that the GFD has any ob- proven to be a highly sensitive test [9] . Anti-en- vious effect on diabetes, it is thought that these domysial antibodies, thought to actually measure patients will have to follow the diet, in order to the same antibody as TGA, appear to be some- prevent all long-term complications of CD. what less sensitive, but more specific, with a spec- Thus, the case for screening type-1 diabetics ificity approaching 100%. for CD seems well founded [6] . • Down syndrome: The prevalence of CD in Down syndrome has been found to be be- Treatment tween 8 and 12%. The majority of Down patients with CD have some gastrointestinal Total lifelong avoidance of gluten ingestion is the symptoms, such as abdominal bloating, inter- cornerstone treatment for CD. Wheat, rye and mittent diarrhea, anorexia, failure to thrive; barley are the grains containing toxic peptides. however, about one third of them do not pres- When children with symptomatic CD adhere to a ent any gastrointestinal symptoms. GFD, they can be expected to resolve their gastrointestinal symptoms typically within a few weeks, 3 showing additional normalization of nutritional Diagnosis measures, improved growth in height and weight (with resultant normal stature), and normaliza- The evidence-based guidelines introduced in tion of hematological and biochemical parame- 2005 by the North American Society for Pediatric ters. Furthermore, treatment with a GFD reverses Gastroenterology, Hepatology and Nutrition the decrease in bone mineralization and the risk (NASPGHAN) [7] describe in great detail a cor- for fractures, and – if instituted early enough in rect diagnostic approach. They substantially fol- the course of the disease – has been proven effec- low the same lines of previous guidelines tive in avoiding the increased mortality rates that proposed by the European Society for Pediatric are otherwise associated with CD [10, 11] . Gastroenterology, Hepatology and Nutrition (ESPGHAN) in 1990 [8] . The algorithm presented in figure 1 describes the suggested diagnostic Prevention approach to a child with predominantly gastrointestinal symptoms. It should be noted that CD There is new evidence showing that CD onset can can effectively be screened by the serum level of be prevented, or at least markedly delayed, when the autoantibody against tissue TGA, which has gluten is introduced in small amounts in geneti-

Celiac Disease 181

Chronic diarrhea and failure to thrive Chronic or recurrent GI symptoms such as: • Abdominal pain • Abdominal distention • Anorexia • Vomiting • Constipation

Obtain tTG and total serum IgA

IgA < 5 mg/dl? Yes Obtain tTG-IgG No

tTG or tTG-IgG if IgA-deficient abnormally high?

No Yes Consult pediatric GE Endoscopic biopsy + EMA

Celiac disease excluded Fig. 1. Diagnostic approach to chil- Consider other diagnoses dren presenting with gastrointestinal (GI) symptoms consistent with Pathology not CD Pathology not CD Pathology of CD Pathology of CD celiac disease (CD). tTG = Tissue EMA normal EMA abnormal EMA normal EMA abnormal transglutaminase; GE = gastroenter- CD excluded Review pathology GFD for 6–12 months CD diagnosed ologist; EMA = anti-endomysial anti- Consider other ? Repeat biopsy Rechallenge and GFD for life body; GFD = gluten-free diet. From diagnoses ? GFD rebiopsy Guandalini [4] . cally predisposed individuals [12] and while the • It occurs more commonly in relatives of celiac infant is still being breastfed [13] , and possibly patients and in some at-risk groups during the 4- to 6-month life window [14] . Addi- • It causes gastrointestinal symptoms, predom- tionally, since the role of gastrointestinal infec- inantly chronic diarrhea with wasting, but tions – especially by rotavirus [15] – in early in- also many extra-intestinal manifestations that fancy has also been proposed, it is possible that can be present alone diffusion of the new anti-rotavirus vaccine may • Once suspected, the patient should be screened also contribute to a reduced prevalence of this with transglutaminase + total serum IgA, and condition. if positive referred to a pediatric gastroenterologist for a confirmatory biopsy before the gluten-free diet is begun Conclusions • A gluten-free diet typically reverses all signs and symptoms within a short time • Celiac disease is an autoimmune inflamma- • Monitoring of the patient to verify ongoing di- tory disorder of the small intestine triggered etetic compliance is fundamental in order to by gluten, and is a very common chronic dis- ensure that all possible complications, includ- ease ing malignancies, are avoided

182 Pediatric Nutrition in Practice References

1 Fasano A, Berti I, Gerarduzzi T, et al: 7 Hill ID, Dirks MH, Liptak GS, et al: 12 Carlsson A, Agardh D, Borulf S, et al: Prevalence of celiac disease in at-risk Guideline for the diagnosis and treat- Prevalence of celiac disease: before and and not-at-risk groups in the United ment of celiac disease in children: rec- after a national change in feeding rec- States: a large multicenter study. Arch ommendations of the North American ommendations. Scand J Gastroenterol

Intern Med 2003; 163: 286–292. Society for Pediatric Gastroenterology, 2006; 41: 553–558. 2 Catassi C, Rätsch IM, Gandolfi L, et al: Hepatology and Nutrition J Pediatr 13 Akobeng AK, Ramanan AV, Buchan I,

Why is coeliac disease endemic in the Gastroenterol Nutr 2005; 40: 1–19. Heller RF: Effect of breast feeding on

people of the Sahara? Lancet 1999; 354: 8 Revised criteria for diagnosis of coeliac risk of coeliac disease: a systematic re- 647–648. disease. Report of a Working Group of view and meta-analysis of observation-

3 Marsh MN: Clinical and pathological ESPGAN. Arch Dis Child 1990; 65: 909– al studies. Arch Dis Child 2006; 91: 39–

spectrum of coeliac disease. Gut 1993; 911. 43.

34: 1740–1741. 9 Hill ID: What are the sensitivity and 14 Norris JM, Barriga K, Hoffenberg EJ, et 4 Guandalini S: Celiac disease; in Guan- specificity of serologic tests for celiac al: Risk of celiac disease autoimmunity dalini S (ed): Essential Pediatric Gas- disease? Do sensitivity and specificity and timing of gluten introduction in troenterology, Hepatology and Nutri- vary in different populations? Gastro- the diet of infants at increased risk of

tion. New York, McGraw-Hill, 2005, enterology 2005; 128(suppl 1):S25–S32. disease. JAMA 2005; 293: 2343–2351. pp 221–230. 10 Corrao G, Corazza GR, Bagnardi V, et 15 Stene LC, Honeyman MC, Hoffenberg 5 Lepore L, Martelossi S, Pennesi M, et al; Club del Tenue Study Group: Mor- EJ, et al: Rotavirus infection frequency al: Prevalence of celiac disease in pa- tality in patients with coeliac disease and risk of celiac disease autoimmu- tients with juvenile chronic arthritis. J and their relatives: a cohort study. nity in early childhood: a longitudinal

Pediatr 1996; 129: 311–313. Lancet 2001; 358: 356–361. study. Am J Gastroenterol 2006; 101: 6 Barker JM: Clinical review: type 1 dia- 11 Metzger MH, Heier M, Mäki M, et al: 2333–2340. betes-associated autoimmunity: natu- Mortality excess in individuals with ral history, genetic associations, and elevated IgA anti-transglutaminase screening. J Clin Endocrinol Metab antibodies: the KORA/MONICA Augs-

2006; 91: 1210–1217. burg cohort study 1989–1998. Eur J

Epidemiol 2006; 21: 359–365.

Celiac Disease 183 Koletzko B. (ed): Pediatric Nutrition in Practice. Basel, Karger, 2008, pp 184–190

3 Nutritional Challenges in Special Conditions and Diseases

3.11 Food Intolerance and Allergy Ralf G. Heine

Key Words Introduction ,Food allergy ؒ Lactose intolerance ؒ Enteropathy food protein-induced ؒ Enterocolitis syndrome, Food allergy represents the failure to achieve or food protein-induced ؒ Proctocolitis, maintain immune tolerance to one or several -food protein-induced ؒ Elimination diet ؒ food proteins [1] . There has been a recent dra Hypoallergenic formula ؒ Amino acid-based matic increase in the incidence of food allergies ؒ ؒ formula Hydrolyzed formula Soy formula in many developed countries (6% children, 2% adults) [2] . Although this increase has been at- tributed to low rates of early childhood infection or exposure to endotoxin (hygiene hypothesis), Key Messages the exact reasons remain unclear. R Food allergy is mediated by an immune reaction Cow’s milk, egg, peanut, tree nuts, fish, soy against food proteins, whereas food intolerances and wheat cause about 95% of food allergies [2, 3] . can be caused by any food constituent and do not involve immunological mechanisms These allergies may present clinically with a R The treatment of food allergies involves strict range of systemic reactions (urticaria, angioede- avoidance of the offending food antigen, either by ma, anaphylaxis), or involve the skin, gut and re- use of a hypoallergenic infant formula or a specific spiratory tract [2, 3] . Multiple food allergies are elimination diet. By contrast, in patients with food common, particularly in early childhood. intolerances small quantities of the offending food Food intolerance is characterized by an ad- ingredient are generally tolerated (dose-response relationship) verse reaction to any (non-protein) food constitu- R Infants and young children with gastrointestinal ent, without interacting with the immune system food allergies, if presenting with persistent vomit- [1] . Examples are malabsorption of fat or carbo- ing or diarrhea, are at high risk of failure to thrive, hydrates which can present with abdominal particularly if there are associated feeding difficul- bloating, pain or diarrhea [4] . Food intolerances ties R Correct identification of food allergies and intoler- may indicate the presence of underlying gastro- ances in infancy and childhood is important in or- intestinal conditions (e.g. celiac disase, intestinal der to prevent growth impairment and nutritional lymphangiectasia) or metabolic disorders (e.g. deficiency states hereditary fructose intolerance). R Close monitoring of dietary intake and growth The treatment of food allergies is based on the parameters, regular re-assessment of persistent al- elimination of specific food proteins until toler- lergies and dietary introduction of tolerated food proteins are essential steps in the nutritional man- ance has developed [3–5] . The treatment of food agement of children with food allergies intolerance follows the same principles but may Copyright © 2008 S. Karger AG, Basel vary according to the underlying condition. Food hypersensitivity

Immune-mediated (T-helper 2 lymphocytes) Non-immune-mediated

Food protein allergy Food intolerance

• Intolerance to ingested Immediate reactions Delayed reactions non-protein food ingredients • Pharmacological reaction, (IgE-mediated) (Non-IgE-mediated or mixed*) dose-dependent • Onset approximately 30–60 • Onset several hours to days • Carbohydrate malabsorption min after food ingestion after food ingestion e.g. lactose, fructose, • Signs and symptoms: • Signs and symptoms: sorbitol, sucrose Oral tingling / itch Feeding diﬃculties (infant) Urticaria / angioedema Vomiting / GER • Fat malabsorption Lip swelling Persistent diarrhea e.g. intestinal lymphangi- Vomiting / diarrhea Failure to thrive ectasia, cystic ﬁbrosis Rectal bleeding • Anaphylaxis • Inborn errors of metabolism • Food protein-induced Above plus any: e.g. hereditary fructose Enteropathy Upper airway swelling intolerance Enterocolitis (FPIES) Wheeze / stridor Proctocolitis Hypotonia / collapse • Idiosyncratic food reactions Cardiorespiratory arrest • Atopic eczema* e.g. vasoactive amines, food additives and preservatives • Eosinophilic esophagitis*

Fig. 1. Classification of adverse reactions to foods. GER = Gastroesophageal reflux; FPIES = food protein-induced enterocolitis syndrome. 3

Gastrointestinal food allergies presenting lergy is mediated by food-specific immunoglob- with persistent vomiting, diarrhea or decreased ulin E (IgE) antibodies [2] . Delayed-onset reac- protein/energy intake may cause failure to thrive tions occur within several hours to days after [4, 5] . The correct and early diagnosis of food al- ingestion and may involve the gut, skin or respi- lergies is therefore important in order to prevent ratory tract. These reactions are cell-mediated nutritional deficiency states and growth impair- (lymphocytes, eosinophils) and typically lack ev- ment [5] . idence of systemic IgE sensitization (skin prick tests and food-specific serum IgE antibodies negative) [2, 3, 6] . Pathophysiology An increasing number of food allergens have been characterized, e.g. ␤ -lactoglobulin in milk, Two main types of food allergy can be distin- ovomucin in hen’s egg or ara c1 in peanut [2] . On guished based on the timing of the clinical reac- each of these proteins, epitope regions have been tion in relation to the food ingestion (fig. 1) [1–3] . mapped that interact with either IgE antibody or Immediate-onset reactions occur within minutes T-cell receptor. Conformational epitopes (with a after ingestion of a food. In these patients the al- 3-dimensional structure) may be inactivated by

Food Intolerance and Allergy 185 Table 1. Gastrointestinal food allergy

Diagnosis Clinical features Investigations Complications Treatment

Food Affects formula-fed infants SPT/RAST-negative Secondary lactose Strict cow’s milk- and protein- (cow’s milk or soy) Intestinal biopsy: intolerance soy-free diet induced Persistent diarrhea villous atrophy and crypt Protein-losing Extensively hydrolyzed enteropathy Occasional vomiting hyperplasia enteropathy formula usually Failure to thrive Duodenal disaccharidases Hypoproteinemia and sufficient; if not reduced (lactase deficiency) edema tolerated, change to Iron deficiency anemia amino acid-based formula

Food Profuse vomiting 2–3 h after SPT/RAST-negative Acute dehydration and Strict avoidance of protein- intake of foods Atopy patch test may hypovolemic crisis in offending food item induced Does not occur in breastfed be positive about 20% of first Requires hypoallergenic enterocolitis infants presentations (may be formula if previous syndrome Common allergens are cow’s mistaken for sepsis or reaction to cow’s milk or (FPIES) milk, soy, grains (wheat, rice) gastroenteritis) soy and chicken Chronic forms may present with persistent diarrhea, vomiting and failure to thrive Low-grade rectal bleeding

Food May occur in breast- or SPT/RAST-negative Iron deficiency anemia In formula-fed infants, protein- formula-fed infants within Rectal mucosa shows uncommon extensively hydrolyzed induced the first weeks of life increased lymphocytes formula; if not tolerated, proctocolitis Low-grade rectal blood loss, and eosinophils, with focal change to amino acid- often mixed in with mucus epithelial ulceration based formula Infants otherwise well and Breastfed infants often thriving respond to maternal elimination diet

heating or acidification. For example, egg allergic and can be fatal, particularly in adolescents and patients may tolerate baked egg while uncooked young adults with concomitant unstable asthma egg causes adverse reactions. [7] . Delayed reactions consist mainly of gastrointestinal or cutaneous reactions [3, 4, 8] . The role Clinical Manifestations of Food Allergy of food allergy in respiratory disorders, such as asthma, is much less well defined. Atopic derma- Food allergy may present with a diverse range of titis with onset within the first months of life is clinical manifestations [3] ( table 1 ). Immediate closely related to food allergy [3] . The gastroin- reactions typically consist of urticaria, angioede- testinal reactions can be divided into food pro- ma, oral tingling or itching, vomiting or diar- tein-induced enteropathy, enterocolitis syndrome rhea. Anaphylaxis is the term used to describe se- (FPIES) and proctocolitis ( table 1 ) [4, 8] . Enter- vere immediate-type reactions with either respi- opathy and proctocolitis may occur in exclusive- ratory compromise (wheeze, stridor, cough) ly breastfed infants [9] , whereas FPIES seems to and/or hypotonia or collapse [7] . Anaphylaxis require direct ingestion of the allergen by the in- may occur in response to small doses of allergen fant [10] . Recently, eosinophilic esophagitis has

186 Pediatric Nutrition in Practice Table 2. Lactose intolerance and its management

Type of Differential diagnosis Treatment Comments lactose intolerance

Primary Congenital Lactose restriction (long-term) Rare

‘Adult-onset’ hypolactasia Lactose restriction (long-term) Common Genetic polymorphism Lactase decline may commence in childhood

Secondary Acute gastroenteritis Short-term lactose restriction Mainly occurs in infancy (lactose-free formula) Typically resolves within 1–2 weeks In breastfed infants continue breast- In very young infants recovery may feeding be delayed If not tolerated, incubation of expressed breast milk with lactase may be successful

Celiac disease Ongoing strict gluten-free diet Beware of false diagnostic label Lactose restriction until intestinal ‘lactose intolerance’ or ‘irritable bowel mucosa restored syndrome’

Food protein-induced Extensively hydrolyzed or amino acid- Cow’s milk-based lactose-free formula enteropathy (non-IgE cow’s based formula may control the malabsorptive milk or soy allergy) symptoms but does not allow mucosal repair (due to ongoing exposure to cow’s milk protein)

Intestinal dysplasia syndromes Depends on severity of disease Rare (e.g. microvillus inclusion May require parenteral nutrition Presents with intestinal failure disease, tufting enteropathy) Lactose restriction, as clinically required

Intestinal mucosal transport Strict avoidance of glucose-, Rare defect of sodium glucose defects (e.g. glucose-galactose galactose-, sucrose- and lactose- transporter SGLT-1 malabsorption) containing foods Presents with profuse watery diarrhea Fructose is tolerated in first week of life 3

been recognized as a condition associated with allergy ( table 2 ) [3, 4] . Dietary lactose restriction food allergy that often responds to dietary elimi- is usually sufficient to control gastrointestinal nation [11] . symptoms. Secondary forms of lactose intolerance may be transient and resolve after the underlying gastrointestinal condition has remitted, L a c t o s e I n t o l e r a n c e e.g. viral gastroenteritis or celiac disease.

Lactose is a disaccharide that is digested into glucose and galactose by the small intestinal brush Investigation border enzyme, lactase. Failure to absorb lactose will result in bacterial fermentation of the sugar, The investigation of food allergy relies on three presenting as flatulence, diarrhea, acidic stools pillars: measurement of food-specific serum IgE and perianal skin excoriation. Lactose malab- antibodies (by radioallergosorbent assay or CAP- sorption should not be confused with cow’s milk FEIA) [2] , skin prick testing [6] and food challenge

Food Intolerance and Allergy 187 Table 3. Investigation of food allergy

Clinical presentation Diagnostic test Comment

Immediate-onset reaction Food-specific serum IgE antibody Diagnosis of IgE food allergy likely if (IgE-mediated) (RAST) or skin prick testing food-specific serum IgE levels or wheal Urticaria/angioedema diameter above diagnostic decision points Oral allergy syndrome [2]. If inconclusive, diagnostic challenges Anaphylaxis are required to confirm allergy or tolerance to food allergen Delayed-onset reaction Gastrointestinal biopsy Food-specific serum IgE antibody and (non-IgE-mediated) Elimination diet and challenge skin prick test negative Food protein-induced Histological appearance of allergic enteropathy, enterocolitis enteropathy similar to celiac disease (FPIES) or proctocolitis Mixed reaction Food-specific serum IgE antibody Elimination diet, as guided by history, (IgE-/non-IgE-mediated) (RAST) or skin prick testing skin prick and patch testing Atopic dermatitis Atopy patch test [11] Eosinophilic esophagitis Esophageal biopsy Esophageal biopsy reveals increased tissue eosinophils (>20 eosinophils per high power field in upper and lower esophagus)

( table 3 ). Recently, atopy patch testing has been in infants with cow’s milk allergy, concomitant al- suggested as a new test for delayed food allergy, lergy to egg, soy or wheat may be present [3]. but its exact role has remained an area of ongoing Several hypoallergenic formulas are available research [12] . Patients with proven food allergy for the treatment of infants with cow’s milk and need to be reassessed on a regular basis in order to soy allergy (table 4). These hypoallergenic for- detect the development of tolerance to the offend- mulas are tolerated by at least 90% of infants with ing food. This will often involve open food chal- cow’s milk allergy [13] . Cross-reactivity between lenges in order to demonstrate tolerance or ongo- cow’s milk and soy is relatively common in in- ing allergies. Due to the risk of anaphylaxis these fants. Soy formula is therefore no longer consid- challenges should be supervised by a trained aller- ered a first-line cow’s milk substitute, particular- gist with access to resuscitation equipment [7] . ly in infants under 6 months [14] . In breastfed infants, a maternal elimination diet may be effective as intact food antigens in breast milk can elicit Dietary Management of Food Allergy allergic manifestations in the infant [9] . However, the clinical benefit of maternal elimination diets In children with specific IgE-mediated food al- is an area of ongoing research. An adequate lergy, e.g. to cow’s milk, egg or peanut, all foods maternal intake of protein and micronutrients containing the offending antigen need to be avoid- (recommended maternal calcium intake 1.2 ed. As allergens are commonly disguised in man- g/day provided as separate portions distributed ufactured food products, this involves careful throughout the day) needs to be maintained. reading of ingredient labels [5] . In infants, aller- There are two main types of hydrolyzed cow’s gies to multiple foods are common. For example, milk formula, partially hydrolyzed and exten-

188 Pediatric Nutrition in Practice Table 4. Formulas used in the treatment of infants with food allergies or intolerances

Type of formula Features and indications

Partially hydrolyzed Contains relatively large cow’s milk protein fragments/peptides cow’s milk-based formula Not suitable for treatment of cow’s milk allergy May play a role in allergy prevention in early infancy Extensively hydrolyzed First treatment choice for formula-fed infants with cow’s milk allergy cow’s milk-based formula Contains small cow’s milk protein peptides (whey-predominant or Residual allergenicity due to trace amount contamination with relatively intact casein-predominant) cow’s milk proteins Infants with previous cow’s milk anaphylaxis require introduction of extensively hydrolyzed formula under medical observation Not tolerated by approximately 10–20% of infants with cow’s milk allergy Amino acid-based Protein-free formula (contains mixture of free amino acids) formula Nutritionally complete formula Treatment of choice if infant is intolerant to extensively hydrolyzed formula (including infants with multiple food allergy of infancy) Soy formula No longer considered appropriate as cow’s milk protein substitute in infants under 6 months of age May play a role in treatment of cow’s milk allergy in older infants Lactose-free cow’s Contains intact cow’s milk protein (same as in standard cow’s milk-based formula) milk-based formula Useful in infants with transient lactose intolerance (e.g. after acute gastroenteritis) Not suitable for infants with secondary lactose malabsorption due to cow’s milk protein-induced enteropathy

sively hydrolyzed formula [13, 15]. Partially hy- are used in the treatment of cow’s milk allergy 3 drolyzed formula may play a role in allergy pre- in formula-fed infants. Soy formula may be vention but it is not suitable for infants with es- suitable in older infants, but cross-reactivity tablished clinical signs of cow’s milk allergy [16] . between cow’s milk and soy protein is relative- These infants require an extensively hydrolyzed ly common formula or, if not tolerated, an amino acid-based • In breastfed infants with food allergic mani- formula [15] . In infants older than 6 months soy festations (e.g. early-onset atopic dermatitis, may also be a suitable alternative [14] . Calcium food protein-induced proctocolitis), a mater- supplementation should be considered in chil- nal elimination diet may control symptoms in dren on dairy-free diets. A dietician is usually re- the infant. Prolonged maternal elimination quired to monitor broad-based elimination diets diets should be supervised by a dietitian for nutritional adequacy [5] . • Lactose intolerance is the most common food intolerance and is treated with a low-lactose diet. Causes of secondary lactose intolerance, C o n c l u s i o n s such as celiac disease, should be considered in the differential diagnosis • Hypoallergenic formulas (extensively hydrolyzed formula or amino acid-based formula)

Food Intolerance and Allergy 189 References

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Allergy Clin Immunol 2004; 113: 832– tious Disease/Food Allergy and Ana- lergy Clin Immunol 2001; 107: 548–553. 836. phylaxis Network symposium. J Aller- 13 American Academy of Pediatrics: Com-

2 Sampson HA: Update on food allergy. J gy Clin Immunol 2006; 117: 391–397. mittee on Nutrition. Hypoallergenic

Allergy Clin Immunol 2004; 113: 805– 8 Sicherer SH: Clinical aspects of gastro- infant formulas. Pediatrics 2000; 106: 819. intestinal food allergy in childhood. 346–349.

3 Hill DJ, Hosking CS, Heine RG: Clinical Pediatrics 2003; 111: 1609–1616. 14 Agostoni C, Axelsson I, Goulet O, et al: spectrum of food allergy in children in 9 Järvinen KM, Mäkinen-Kiljunen S, Soy protein infant formulae and follow- Australia and South-East Asia: identifi- Suomalainen H: Cow’s milk challenge on formulae: a commentary by the cation and targets for treatment. Ann through human milk evokes immune ESPGHAN Committee on Nutrition. J

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4 Heine RG: Pathophysiology, diagnosis allergy. J Pediatr 1999; 135: 506–512. 352–361. and treatment of food protein-induced 10 Nowak-Wegrzyn A, Sampson HA, 15 de Boissieu D, Matarazzo P, Dupont C: gastrointestinal diseases. Curr Opin Wood RA, Sicherer SH: Food protein- Allergy to extensively hydrolyzed cow

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190 Pediatric Nutrition in Practice Koletzko B. (ed): Pediatric Nutrition in Practice. Basel, Karger, 2008, pp 191–195

3 Nutritional Challenges in Special Conditions and Diseases

3.12 Regurgitation and Gastroesophageal Reflux Tejas Mehta ؒ Benjamin Gold

Key Words ease (GERD), however, refers to the troublesome Gastroesophageal reflux disease ؒ Regurgitation symptoms and complications that may develop secondary to persistent GER [1] . GERD complications include esophagitis, growth disturbance, Key Messages feeding aversion, and respiratory disease. R Though gastroesophageal reflux disease (GERD) Although the physiology of GER is different in frequently resolves in pediatric patients, most children and adults, the primary pathophysio- commonly by 1 year of age, it can become a chron- logic mechanisms resulting in GERD are similar ic condition in some children R Though regurgitation plus one or more trouble- in all age groups, even as early as 38 weeks gesta- some symptoms (e.g. persistent irritability, feeding tion. These mechanisms include transient relax- refusal) is the predominant symptom in infantile ation of the lower esophageal sphincter (LES), in- GERD as opposed to older children who may man- hibition of esophageal body peristalsis, and an ifest with abdominal pain, both groups can present inappropriate decrease in LES resting tone in the with extra-esophageal symptoms (e.g. respiratory absence of swallowing [2–4] . manifestations) R Though GERD is optimally diagnosed by clinical Though virtually all infants regurgitate, about suspicion and a response to acid suppression ther- 3% of normally developing infants have clinically 3 apy, diagnostic testing such as upper endoscopy significant GERD. In most infants, GER symp- may be indicated to assess GERD-related complica- toms, especially regurgitation, peak by 2–4 tions and/or its masqueraders (e.g., eosinophilic months and resolve by 1 year of age [5] . Contrary esophagitis) R Conservative measures may be adequate to treat to previous beliefs, GERD may not be outgrown. uncomplicated, mild GERD in infants; however, Recent studies indicate that persistent GERD in when therapy is necessary for 2 weeks or longer, children up to age 2 years may recur in the pre- proton pump inhibitors are the treatment of choice adolescent or older child [6] . Additionally, once in children Copyright © 2008 S. Karger AG, Basel GERD is clinically or endoscopically evident in a child or adolescent, it can be a chronic life-long condition in a substantial percentage of these patients. Introduction Although no population-based epidemiological studies have been performed, for reasons that Gastroesophageal reflux (GER) refers to the pas- remain unexplained GERD is being increasingly sage of gastric contents into the esophagus or recognized in children particularly in countries oropharynx. GER can be a daily, normal physio- where GERD was relatively uncommon [7] . There logical occurrence. Gastroesophageal reflux dis- is also a rising prevalence of severe GERD-related Table 1. Concerning age-specific manifestations of gas- 70 67% Regurgitation more trointestinal reflux disease than 1 time per day 60 50% Heartburn Infants Older children and adolescents 50

40 Poor weight gain Early morning nausea Recurrent vomiting Abdominal discomfort 30 21% 22% Feeding refusal Burps that burn 20 Generalized irritability Substernal pain Arching Heartburn 10 5% 2% 4% Percent of infants and children Apnea/bradycardia Recurrent vomiting 0 0–3 4–6 7–9 10–12 3–9 10–17 >18 Extra-esophageal manifestations Age, months Age, years – Wheezing/asthma/chronic cough – Hoarseness Fig. 1. Prevalence of regurgitation in infants and heart- – Dental erosions burn in children, by age. Adapted from the American – Chronic sore throat Journal of Medicine [1] and Archives of Pediatric and Ad- – Recurrent pneumonia olescent Medicine [5, 9]. Adapted from Gold [1]. outcomes such as erosive esophagitis and Bar- rett’s esophagus. Thus, earlier detection and However, irritability is not very specific and often treatment of GERD in children may lead to better is a poor indicator of pathologic acid reflux. In outcomes later in life. This review will describe addition, the combination of arching of the back, the symptoms, diagnosis, and management of torsion of the neck, and lifting of the chin sug- this chronic disease in children. gests Sandifer syndrome. This GERD-associated condition, often confused with torticollis, has its peak occurrence at 18–36 months of age. Con- S y m p t o m s versely, the presence of rectal bleeding, eczema, and a family history of atopic disease may suggest Normal physiological GER is substantially more cow’s milk protein allergy rather than GERD. common in the first year of a child’s life com- GERD-specific symptoms in childhood vary pared to adults. Gastric contents may frequently by age and change in character as the child gets reflux into the esophagus (30 8 20 times daily) older, if GERD persists over time. Extra-esopha- [8] . Normal regurgitation appears to peak at 2–4 geal manifestations of GERD may be more com- months of age and soon after 1 year of age re- mon than previously believed and can be the only solves ( fig. 1). symptoms of GERD. Of the extra-esophageal Beyond this age, persistent regurgitation is re- GERD-associated conditions, head and neck placed by other GERD-related symptoms, in- manifestations include dental erosions, pharyn- cluding abdominal pain, morning nausea or dis- gitis, and vocal cord disorders such as laryngitis. comfort [9] . Heartburn, a cardinal symptom of Respiratory manifestations include nocturnal GERD in adults, generally does not manifest un- cough or wheezing, reactive airway disease, asth- til adolescence. Table 1 lists manifestations that ma and recurrent pneumonias. Although it is should raise concern for GERD. Infants can pre- postulated that apnea is a sequelae of GERD, sent with frequent regurgitation, vomiting, poor studies showing benefit of acid suppression in in- weight gain, feeding refusal, and irritability. fants with apnea are lacking.

192 Pediatric Nutrition in Practice D i a g n o s i s

Abdominal symptoms A thorough history and physical examination Respiratory symptoms (e.g. nocturnal cough) Laryngopharyngeal symptoms (e.g. laryngitis) can be the key to diagnosis of GERD, with specific attention to the child’s age, as well as the o Lifestyle changes character and frequency of GERD-related symp- • Weight loss toms. The original North American Society for • Head elevation • Avoidance of passive smoking Pediatric Gastroenterology, Hepatology, and Nu- o Trial of PPI for 4–6 weeks trition clinical practice guidelines for GERD in children recommended that a trial of acid suppression should be considered based on history Symptoms Symptoms resolve persist and physical examination (fig. 2). The proton pump inhibitor (PPI) test has been effective in adults, with resolution of symptoms being the di- Discontinue medication after agnostic test for GERD. additional 8–12 weeks of In the U.S., a random sample of the American treatment Academy of Pediatrics was recently surveyed on their knowledge, attitudes and practice styles Consider referral to with respect to pediatric GERD, and responded gastroenterologist for Symptoms recur EGD with biopsies and/or that, if testing for GERD in children, the upper additional testing based on diﬀerential diagnosis gastrointestinal series (UGI) would be their first test of choice [10] . However, the UGI is a reasonable approach to assess for anatomic abnormali- Fig. 2. Algorithm for the evaluation and management of ties (e.g., hiatal hernia, vascular rings, intestinal suspected GERD in older children. PPI = Proton pump malrotation) amenable to surgical correction. inhibitor; EGD = esophagogastroduodenoscopy. Unfortunately, the UGI is at best 50% sensitive and specific for diagnosing GERD [11] . 3 In cases where the diagnosis of GERD may not be obvious based on symptoms, esophageal pH monitoring for 48–72 h, allowing participation in monitoring can accurately measure the frequen- normal daily activities. Validation of both the cy and duration of acid exposure. In order to wireless pH metry system and impedance is still ‘prove’ and document GERD, a symptom diary is lacking in pediatric age groups. essential. In addition, the pH metry study may If GERD symptoms do not resolve or return also be useful in the child who has an incomplete after a 2- to 4-month trial of acid suppression, re- symptom response and/or intermittent symptom ferral to the pediatric gastroenterologist for esoph- breakthrough despite therapy. However, studies agogastroduodenoscopy (EGD) with biopsies is demonstrated variability of pH monitoring in suggested. In addition, when hematemesis or oc- over 34% of subjects, and pH-monitoring systems cult bleeding occurs in the face of GERD symp- cannot measure non-acid reflux. Thus, multi- toms, EGD may be indicated to assess the pres- channel intraluminal impedance monitoring, ence and severity of GERD. EGD can also detect particularly when combined with pH metry, may erosive (macroscopic) or histologic (microscopic) be the most accurate way of evaluating acid and esophagitis, strictures, Barrett’s esophagus, and non-acid reflux. For patients above 6 years of age, eosinophilic esophagitis, a potential GERD mas- wireless pH metry systems provide continuous querader [12, 13] . Other diagnostic modalities in-

Regurgitation and Gastroesophageal Reflux 193 Recurrent regurgitation in child ≤12 months of age

Uncomplicated GER or GERD in a Alarming symptoms (poor weight gain, thriving infant feeding refusal, irritability, apnea/bradycardia, respiratory issues)

o Upright positioning, frequent and smaller feeds o Consider thickened feeds or 2–4 week trial of hypoallergenic formula o Consider trial of prokinetic, H2RA or PPI Fig. 3. Algorithm for the evaluation and management of suspected o Referral to gastroenterologist o Consider additional diagnostic GERD in infants. H2RA = H 2 receptor Symptoms persist or do not resolve testing and/or: antagonist; PPI = proton pump in- by 12–18 months of age • UGI series hibitor; EGD = esophagogastroduo- • EGD + biopsies • Esophageal pH monitoring denoscopy; UGI series = upper gastrointestinal series. clude esophageal manometry (used to document infant death syndrome. However, these ap- transient LES relaxations and esophageal body proaches may be ineffective in resolving the acid- peristalsis abnormalities), nuclear scintigraphy, related consequences of reflux. If milk protein in- and esophageal ultrasound, but there are few stud- tolerance or allergy is suspected, a 2- to 4-week ies justifying their use routinely in children. trial of protein (partial whey or casein) hydrolysate formula should be considered (fig. 3 ). When pharmacotherapy is required, H2 -re- T r e a t m e n t ceptor antagonists may be effective for mild GERD in children. However, tachyphylaxis de- The primary goals of treatment are to resolve velops quickly with symptom recurrence within symptoms, improve overall quality of life, and re- days to a few weeks of treatment. Thus PPIs are solve and prevent complications of GERD. In becoming the preferred treatment for GERD in ‘uncomplicated’ GERD, conservative measures infants and children. PPIs have been shown in such as thickening the formula, giving smaller pediatric studies to be safe and effective. Omepra- feeds more frequently, and upright positioning zole at doses ranging from 0.5 to 4 mg/kg has for at least 30 min after feeds may be sufficient to been shown to decrease GERD symptoms in chil- decrease regurgitation. In addition, thickening dren after only 14 days [14] . Lansoprazole given can increase the caloric density of the formula, at doses of 15 or 30 mg once or twice daily, based which may benefit infants who have weight gain on weight, resulted in resolution of erosive esoph- issues as a result of GERD (1 tablespoon of rice agitis after 3 months of treatment in one study cereal per 2 ounces of formula increases the ca- [15] . Recently, esomeprazole has been shown to loric density to 27 kcal per ounce). Prone posi- improve GERD-related symptoms and resolve tioning may decrease regurgitation but is not rec- extra-esophageal manifestations after 8–12 weeks ommended due to the increased risk for sudden of therapy in children 12–17 years of age [16] . In

194 Pediatric Nutrition in Practice general, studies have suggested beginning PPI • GERD can resolve in many children, particu- treatment at a dose of 1 mg/kg per day divided larly those ! 1 year of age, but sometimes per- into one or two doses. Prokinetics such as meto- sists clopramide are effective in approximately 50% of • GERD is diagnosed based on clinical suspi- children with GERD; however, they can be asso- cion (thorough history and physical examina- ciated with neurological side effects. Thus, usage tion) followed by a course of empiric therapy, should be limited to children with regurgitation- which often resolves symptoms. Diagnostic predominant symptoms. Finally, anti-reflux testing, such as an upper gastrointestinal se- surgery should be considered in children with ries to rule out anatomic abnormalities or en- complications of GERD such as aspiration (with doscopy for gastrointestinal bleeding and re- or without oral-pharyngeal dysfunction), Bar- fractory symptoms, should be utilized with a rett’s esophagus, and esophageal strictures. Pre- working differential diagnosis dictors of fundoplication success are response to • When mild, GERD is often treatable conser- medical therapy and surgeon experience [11] . vatively. Suspected milk protein intolerance, which can masquerade as GERD in infancy, necessitates a trial of protein hydrolysate for- C o n c l u s i o n s mula • Proton pump inhibitors are superior for symp- • Gastroesophageal reflux disease (GERD) is tomatic relief and mucosal healing, and are less easily diagnosed under 1 year of age where safe for long-term use, with an adverse event physiologic reflux may occur instead profile similar to adults

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569–572. 45: 56–64. traesophageal symptoms of GERD. J 6 Martin A, Pratt N, Kennedy J: Natural 11 Rudolph CD, Mazur LJ, Liptak GS: Pediatr Gastroenterol Nutr 2007, in history and familial relationships of Guidelines for evaluation and treat- press.

Regurgitation and Gastroesophageal Reflux 195 Koletzko B. (ed): Pediatric Nutrition in Practice. Basel, Karger, 2008, pp 196–199

3 Nutritional Challenges in Special Conditions and Diseases

3.13 Feeding Disorders Richard M. Katz

Key Words items (pica). This term is often mistaken for the Feeding disorders ؒ Digestive disorders ؒ eating disorders of anorexia nervosa and bulimia .[Gastroesophageal reflux ؒ Food selectivity ؒ more commonly seen in adolescents [1 Eating disorders Feeding disorders are surprisingly common in children. It has been estimated that 25–35% of normal children have a mild feeding disorder, Key Messages and up to 80% of children with developmental R Children with feeding disorders are a heteroge- disabilities have difficulty in feeding. Further neous group analysis of prevalence indicates that half of all R Feeding irregularities in healthy children are often toddlers are not consistently hungry at mealtime, temporary R In others, however, the problem may be persis- and about one third show food selectivity [2] . Se- tent vere feeding problems are noted with greater fre- R Feeding disorders have multiple etiologies which quency in children with physical disabilities (26– include medical, behavioral, nutritional, psycho- 90%) and among those with medical illness and logical and environmental factors prematurity (10–49%) [3–5]. R Given that children’s feeding progresses in a biologic, maturational, learning and nurturing envi- Children with feeding disorders are a hetero- ronment, feeding disorders are best diagnosed geneous group but can be broadly divided into and treated by multifaceted approaches that en- three categories: children who are healthy and compass evaluation of these processes without significant comorbid conditions; those Copyright © 2008 S. Karger AG, Basel who have digestive disorders (gastroesophageal reflux being the most common), and those with special needs, especially chronic neurologic dis- Introduction orders. Feeding irregularities in healthy children are often temporary, and most resolve spontane- ‘Feeding disorders’ is a term that describes chil- ously. In others, however, the problem may be dren who experience difficulty in consuming ad- persistent and require intensive professional equate or proper nutrition by mouth. This in- care. cludes children who will not eat (food refusal), Feeding disorders have multiple etiologies those who have abnormal swallowing (dysphagia which include medical, behavioral, nutritional, or impaired feeding), those who eat too much psychological and environmental factors (ta- (hyperphagia) and those who eat inappropriate ble 1). However, rarely does a child with a feeding Table 1. Conditions associated with pediatric feeding disorders

Total food refusal Motility disorders Food refusal by volume Achalasia Food refusal by texture Diffuse esophageal spasm Food refusal by type Chronic pseudo-obstruction Bottle dependency Systemic lupus erythematosus Maladaptive behaviors Polymyositis Disorders of the oral and pharyngeal phases of Genetic disorders swallowing Prader-Willi syndrome Anatomic lesions Trisomy 21 Cleft lip and/or palate Cornelia de Lange syndrome Pierre-Robin sequence Velo-cardio-facial syndrome Choanal atresia Rett syndrome Laryngeal clefts Metabolic disorders Macroglossia Urea cycle abnormalities CHARGE association Hereditary fructose intolerance Acquired structural abnormalities Hypothyroidism Dental caries Miscellaneous Tonsillar hypertrophy Gastroesophageal reflux Viral/inflammatory stomatitis Constipation Retropharyngeal mass Gas-bloat syndrome Candida stomatitis Dumping syndrome Cardiopulmonary effects Food allergies Chronic lung disease Sensory loss (visual/auditory impairment) Complex congenital heart disease Reactive airway disease Tachypnea Neuromuscular disorders Familial dysautonomia Cerebral palsy disorder have a single etiology causing poor oral Pseudo-bulbar palsy nutrition. Given that children’s feeding progress- Bulbar atresia or palsy es in a biologic, maturational, learning and nur- 3 Cranial nerve anomalies Muscular dystrophic disorders turing environment, feeding disorders are best Arnold-Chiari malformation diagnosed and treated by multi-faceted approach- Myelomeningocele es that encompass evaluation of these processes. Intracranial mass lesions This is best accomplished with an interdisciplin- Disorders of the esophageal phase of swallowing Cricopharyngeal achalasia ary variety of pediatric specialists including phy- Tracheoesophageal fistula sicians, nurse practitioners, nutritionists, occu- Esophageal mass pational therapists, speech therapists, psycholo- Esophageal stricture gists and social workers. This team must establish Esophageal web a diagnostic and therapeutic plan based on a Esophageal rings Vascular rings/aberrant vessels careful prenatal, birth and neonatal, and current Foreign bodies history. This includes the onset, course, frequen- Disorders of the lumen cy of feeding patterns and behaviors as well as Peptic esophagitis assessing medical conditions that may be associ- Candida esophagitis Viral esophagitis ated with the feeding difficulties. Medical issues ‘Pill’ esophagitis are commonly associated with pediatric feeding Inflammatory bowel disease disorders and may be etiologic factors or comor- Behcet syndrome bid conditions.

Feeding Disorders 197 Table 2. Diagnostic evaluation of patients with feeding Table 4. Development of feeding disorders disorders Predisposing factors Detailed history and physical examination Temperament of child and caregivers Upper gastrointestinal contrast radiography Recurrent illness Esophogram Low resilience Small bowel follow through Parental depression or poor coping ability Video-fluoroscopic swallow study Precipitating factors Gastric emptying study Acute illness pH monitoring Injury Esophagogastroduodenoscopy with biopsies Pain Antroduodenal manometry Child endangerment or neglect Fiberoptic endoscopic evaluation of Perpetuating factors swallowing Continued pain or discomfort Complete blood count Reinforcement from behaviors Comprehensive metabolic panel Thyroid function RAST analysis for food allergies Skin test for food allergies Plasma amino acids Urine organic acids strategies are available to their caregivers to im- Karyotype prove mealtime behaviors and minimize the food refusal or food selectivity behavior. These include establishing mealtime consistency, minimizing meal disruption, repeatedly presenting the food on a number of routines, and developing Table 3. Oral motor assessments and therapy a positive reinforcement pattern for appropriate 1 Assessment of swallowing function and safety mealtime behavior. 2 Clinical evaluation – assess head and neck position, Therapy directed at resolving complex feed- tongue and jaw movement, dentition, airway ing issues requires the professional team to iden- sounds, speech assessment and seating position tify the predisposing, precipitating and perpetu- 3 Modified barium swallow assesses oral, pharyngeal and upper esophageal phases of swallowing ating factors involved in the feeding pattern of 4 Texture assessment abnormal eating behaviors [6] (table 4). Once air- Non-nutritive oral stimulation way safety has been established, a variety of treat- Decreases oral hypersensitivity ment approaches are available to increase oral Facilitates management of secretions intake, advance food texture and, if possible, Establish or retrain swallowing mechanism progress to self-feeding. Medical therapies are di- Develop oral motor movement for sound production rected toward alleviating organically based feeding difficulties and often may require medication, surgical intervention and employing alternate routes of nutrition such as enteral tube feeds Evaluations also include careful physical ex- to deliver sufficient calories. aminations and diagnostic studies ( table 2 ) to Initial therapy is aimed at making changes to help determine associated medical conditions feeding routines, schedules, environment and and evaluate swallowing anatomy and safety (ta- skills of the child’s caregivers. This includes ad- ble 3 ). dressing issues such as sleep patterns, bowel hab- Most children with feeding disorders will its and sibling interactions. Dieticians are an in- spontaneously improve with time. However, tegral part of the treatment process as often rela-

198 Pediatric Nutrition in Practice tively simple concepts of food preparation, food The importance of understanding and treat- storage and nutritional value of foods are poorly ing oral-motor issues in children with feeding understood. In some circumstances, enteral feed- difficulties cannot be underestimated. Oral mo- ing management is an essential part of the treat- tor techniques to improve muscle tone and pos- ment process and adjustments should be made tural control provide important foundations to prior to the development of a more intrusive the eating process. The use of adaptive seating treatment procedure. systems is a key component to feeding children Specialized feeding is not limited to routes of with physical disabilities, providing head, neck feeding. The diet itself is crucial to maintain the and truncal support. wellbeing of the child. This includes appropriate understanding of sound nutritional guidelines, and also includes the use of specialized formulas Conclusions to deliver appropriate nutrients to the gastrointestinal tract due to impairment of the gastroin- • Feeding disorders in young children are sur- testinal tract or specific metabolic needs, e.g. ke- prisingly common togenic diet. • Feeding disorders are multifactorial and oc- Applied behavior analysis is utilized to treat cur as a result of medical, sensory, social and feeding problems including food refusal, food se- environmental reasons lectivity and disruptive mealtime behaviors. Ap- • Enteral feeding should be utilized for those plied behavior analysis can be used successfully who are unable to eat orally or who are very to treat caregiver mismanagement of feeding is- malnourished sues. These principles include establishment of • While on enteral feeds, children should con- systematic feeding routine, altering the texture of tinue to receive nutritive and non-nutritive food presented to the rewarding appropriate eat- oral motor therapy ing behavior and ignoring food refusal behavior. • Caregiver training and education are essential Negative or punishing behavior is discouraged. for maintenance of feeding success Parent training involves instruction, discussion, • Most children with feeding disorders can be 3 skill acquisition, role playing and practice tech- effectively treated, but often require an expe- niques with trained clinicians. rienced feeding team

References

1 Marchi M, Cohen P: Early childhood 3 Reilly S, Skuse D, Problete X: Preva- 5 Thommessen M, Heidberg A, Kase BF, eating behaviors and adolescent eating lence of feeding problems and oral mo- et al: Feeding problems, height and disorders. J Am Acad Child Adolesc tor dysfunction in children with cere- weight in different groups of disabled

Psychiatry 1990;29: 112–117. bral palsy: a community survey. J children. Acta Paediatr Scand 1991; 80:

2 Reau NR, Senturia YD, Lebailly SA, Pediatr 1996; 129: 877–887. 527–533. Christoffel KK: Infant and toddler 4 Douglas JE, Byron M: Interview data 6 Katz R, Manikam R, Schuberth L: Pedi- feeding patterns and problems: norma- on severe behavioural eating difficul- atric feeding problems; in Shiles ME, tive data and a new direction. Pediatric ties in young children. Arch Dis Child Shike M, Ross AC, Caballero B (eds):

Practice Research Group. J Dev Behav 1996; 75: 304–308. Modern Nutrition in Health and Dis-

Pediatr 1996; 17: 149–153. ease. Baltimore, Lippincott, Williams & Wilkins, 2006, pp 875–880.

Feeding Disorders 199 Koletzko B. (ed): Pediatric Nutrition in Practice. Basel, Karger, 2008, pp 200–203

3 Nutritional Challenges in Special Conditions and Diseases

3.14 Preterm and Low Birthweight Infants Ekhard E. Ziegler

Key Words limitations is immaturity of the intestinal tract. It necessitates the use of parenteral nutrition dur- ,Nutrient requirements, high ؒ Intestinal tract immaturity of ؒ Parenteral nutrition ؒ Breast milk, ing the early days and weeks of life in infants with fortification early preterm birth. Parenteral nutrition carries various risks, including the risk of infections and the risk of metabolic complications. Immaturity Key Messages of the intestinal tract is also the reason why pre- R Nutrient administration, though technically diffi- term infants are susceptible to necrotizing en- cult, must be initiated promptly after birth to avoid terocolitis (NEC). Although enteral feedings per adverse effects of undernutrition se do not cause NEC, feedings increase the risk of R Early preterm birth with immaturity of the intestinal tract necessitates use of parenteral nutriton un- NEC and therefore are used very cautiously. The til the intestinal tract is able to accept full feed- multiple risks associated with the provision of ings nutrients explain why the nutrient intakes re- R Enteral feedings should be started promptly (tro- ceived by preterm infants tend to fall short of re- phic feeds) and advanced as permitted by matura- quirements. The growth failure that results from tion of intestinal motility inadequate nutrient intakes is predictive of im- R Preferred feeding is breast milk (mother’s own or donated), special formulas for preterm infants are paired neurocognitive development later in life. second choice Efforts to improve nutrient intakes are therefore R Breast milk must be fortified with nutrients to meet important. the high nutrient needs of preterm infants; com- Nutritional support of preterm infants occurs mercial fortifiers provide most nutrients (with the in two distinct phases which each carry their own exception of protein) in adequate amounts risks and challenges. During the early phase nu- Copyright © 2008 S. Karger AG, Basel trients are predominantly provided via the parenteral route, while enteral (trophic) feedings assist the immature intestinal tract in its gradual Introduction maturation but provide few nutrients to the infant. During the late phase infants are on exclu- Provision of adequate nutrition for preterm in- sive enteral feedings and are expected to grow fants presents unique challenges. Meeting the normally. If provided the necessary nutrients, very high nutrient needs of these infants ( table 1 ) preterm infants may also show catch-up growth, is difficult and fraught with risks related to the i.e., are making up some of the ground typically physiological limitations of these infants [for an lost during the early phase. overview see 1, 2]. The most important of these Table 1. Requirements for protein and energy (based on factorial approach)

Body weight, g 500–700 700–900 900–1,200 1,200–1,500 1,500–1,800

Fetal weight gain, g/day 13 16 20 24 26 Fetal weight gain, g/kg per day 21 20 19 18 16 Protein, g/kg Inevitable loss 1.0 1.0 1.0 1.0 1.0 Growth (accretion) 2.5 2.5 2.5 2.4 2.2 Required intake Parenteral 3.5 3.5 3.5 3.4 3.2 Enteral 4.0 4.0 4.0 3.9 3.6 Energy, kcal/kg Loss 60 60 65 70 70 Resting expenditure 45 45 50 50 50 Miscellaneous expenditure 15 15 15 20 20 Growth (accretion) 29 32 36 38 39 Required intake Parenteral 89 92 101 108 109 Enteral 105 108 119 127 128 Protein/energy, g/100 kcal Parenteral 3.9 3.8 3.5 3.1 2.9 Enteral 3.8 3.7 3.4 3.1 2.8

For normal or catch-up growth to happen, the As this maturation progresses, a gradual shift 3 infant must receive the requisite amounts of nu- occurs from exclusive parenteral nutrition to trients. Failure to receive adequate amounts of exclusive enteral nutrition. The early nutrition nutrients, principally protein, leads to growth period ends when full enteral feedings are failure. The amounts of protein and energy re- reached. quired for normal growth are summarized in table 1 . The requirements for catch-up growth are Parenteral Nutrition higher (see below). In immature infants, parenteral nutrition should begin immediately (within 2 h of birth) and must provide, as a minimum, glucose, amino acids, Early Nutrition electrolytes, calcium, phosphorus and magnesium. It is acceptable for the amount of amino During the immediate postnatal period, the ob- acids to be less than 3.5 g/kg per day ( table 1 ) for jective of nutritional support is twofold, to pro- a short period. The initiation of lipid emulsion is vide an uninterrupted flow of nutrients so that less urgent and a delay for up to 48 h is probably the anabolic state can continue with minimal in- acceptable. The initial rate need not be more than terruption, and to support the immature gastro- 0.5 g lipids/kg per day. The efficacy and safety of intestinal tract in its transition to a mature state. parenteral nutrition starting immediately after

Preterm and Low Birthweight Infants 201 birth have been demonstrated [3] . Full parenteral not require cessation of feedings as long as there nutrition should be maintained until enteral are no signs suggestive of NEC. The use of tro- feedings of 20 ml/kg per day are regularly toler- phic feedings leads to earlier establishment of ated. As feedings are increased, the amount of full feedings and to earlier hospital discharge parenteral nutrition is tapered, with total (paren- without a significant increase in NEC [5] . Feed- teral plus enteral) intake of nutrients always at ing volumes should be increased by 20 ml/kg full level. each day or less. Although more rapid increases are safe, intestinal maturation requires time and Enteral Nutrition more rapid increases are not recommended. The anatomically and functionally immature in- When feeding volumes are 80–100 ml/kg per testine can undergo maturation in a relatively day, fortification of breast milk should be initi- short time, given the necessary stimulation is ated. Parenteral nutrition should be discontin- provided in the form of trophic feedings. Enteral ued when enteral feedings provide more than (at least trophic) feedings should be started on the 90% of required nutrient intakes. first day of life. Feeding volumes initially may be as low as 2 ml every 6 or 4 h. In very premature infants, stimulation of the gut is initially the sole L a t e N u t r i t i o n objective of enteral feedings. Motility serves as a marker of gut maturation and is monitored clini- The late period begins when full feedings are es- cally through the assessment of gastric residuals. tablished and parenteral nutrition is discontin- As gastric emptying improves, it is assumed that ued. Feedings are fortified human milk or, when the ability to digest and absorb nutrients also is not available, special formulas with a protein improving. Gastric emptying thus serves as an content of 3 g/100 kcal. Breast milk must be forti- important clinical guide in early enteral feeding. fied to increase the protein and mineral content The risk of NEC is quite low with trophic feed- in order to meet the preterm infant’s high needs. ings but increases subsequently as feeding vol- Any of the commercially available fortifiers are umes increase. suitable, although all provide less than an opti- The preferred trophic feeding is maternal mal amount of protein. The objective of nutrition milk or, when not available, donor milk. Donor is to allow growth to proceed parallel to intra- milk may also be used to supplement maternal uterine growth channels. Also, infants who have colostrum, which is usually available only in fallen behind during the early phase may be able small amounts during the first few days. Donor to show catch-up growth. The protein and energy milk is pasteurized and free of viruses such as intakes listed in table 1 are needed to support HIV and cytomegalovirus. Although pasteuriza- growth at the intrauterine rate. If the infant is to tion diminishes some of its protective factors, catch up in growth, intakes must be further in- donor milk still is protective against NEC [4] and creased by 10–20%. is preferable to formula. Preterm formula must Providing the required protein intake is im- be used when human milk is not available. Feed- portant but difficult. If the infant is fed formula, ing volumes may be kept low for several days or the protein/energy ratio (3.0 g/100 kcal) tends may be increased as gastric residuals diminish. to be close to the required ratio, except for At each new level, the adequacy of gastric empty- very small infants. If the infant is fed fortified ing (absence of gastric residuals) must be ascer- human milk, the protein/energy ratio is almost tained before the feeding volume is further in- always too low and hence the protein intake increased. The presence of gastric residuals does adequate [6] . The reason is that fortifiers are de-

202 Pediatric Nutrition in Practice signed to raise the protein/energy ratio from 2.1 Conclusions g/100 kcal (typical of human milk at 2 weeks after parturition) to about 3.0 g/100 kcal. As ta- • Nutritional support must begin at birth and ble 1 shows, such a protein/energy ratio is ade- should be complete at all times quate for larger infants only. More importantly, • The smaller the infant, the more important it the protein content of human milk after 2 weeks is not to allow a nutrient deficit to accrue of lactation is less than 2.1 g/100 kcal and the • Parenteral nutrition initially is the sole pro- protein/energy ratio of fortified milk is there- vider of nutrition in very preterm babies fore much less than 3.0 g/100 kcal and inade- • In very preterm babies, enteral (trophic) feeds quate for small infants (! 1,500 g). For small in- initially have the sole function of supporting fants, additional protein should be added. This the immature gastrointestinal tract in its tran- can be done by adding more than the standard sition to a mature state amount of fortifier (e.g., 50% more) or by adding • Once gastric residuals have subsided, feedings extra protein. A method for BUN-guided for- are advanced slowly until full feedings are tification has been described by Arslanoglu et reached al. [7] . • Preferred feeding is breast milk, which must be fortified with protein and minerals to meet the high needs of preterm infants • Routine fortification is inadequate for very small infants and additional protein should be provided

References

1 Tsang RC, Uauy R, Koletzko B, Zlotkin 3 te Braake FWJ, van den Akker CHP, 5 Tyson JE, Kennedy KA: Trophic feed- SH (eds): Nutrition of the Preterm In- Wattimena DJL, et al: Amino acid ad- ings for parenterally fed infants. fant. Scientific Basis and Practical ministration to premature infants di- Cochrane Database Syst Rev 2005; 3: 3 Guidelines. Cincinnati, Digital Educa- rectly after birth. J Pediatr 2005; 147: CD000504. tional Publishing, 2005. 457–461. 6 Ziegler EE: Breast-milk fortification.

2 Ziegler EE, Thureen PJ, Carlson SJ: Ag- 4 Boyd CA, Quigley MA, Brocklehurst P: Acta Paediatr 2001; 90: 720–723. gressive nutrition of the very low birth- Donor breast milk versus infant formu- 7 Arslanoglu S, Moro GE, Ziegler EE:

weight infant. Clin Perinatol 2002; 29: la for preterm infants: systematic re- Adjustable fortification of human milk 225–244. view and meta-analysis. Arch Dis Child fed to preterm infants: does it make a

Fetal Neonatal Ed 2007; 92:F169–F175. difference? J Perinatol 2006; 26: 1–8.

Preterm and Low Birthweight Infants 203 Koletzko B. (ed): Pediatric Nutrition in Practice. Basel, Karger, 2008, pp 204–207

3 Nutritional Challenges in Special Conditions and Diseases

3.14.1 Feeding the Low Birthweight Infant in a Resource-Restricted Environment Fredrick N. Were

Key Words ments must always be derived from milk prepa- Nutrient needs, high ؒ Enteral feeds ؒ Crystalloids ؒ rations, even in the smallest or sickest babies, if Mothers’ milk ؒ Feed volume ؒ Micronutrients total parenteral nutrition is not available. The milk produced by mothers who deliver prematurely (PM) contains 1.9 (range 1.1–3.5) g protein Key Messages and 75 kcal/100 ml during the first 14–28 days R Enteral feeds must be started early and aggressive- following delivery [2] ; however, this drops to ly increased to nutritionally adequate volumes 0.9 g protein and ! 70 kcal thereafter [2] . Alterna- whenever the option of total parenteral nutrition is tive feeds available in poor countries include not available cow’s or standard formula with grossly inade- R The use of large total daily feed volumes in smaller more frequent aliquots is helpful when high-den- quate nutritional value (table 1). When available, sity nutrient milk preparations are not available to breast milk fortification and preterm formula provide adequate nutrition at lower volumes (PTF) are used to easily achieve the needs of small R Whenever possible, breast milk fortification or sup- infants [3, 4]. The main challenge in resource-re- plemental preterm formula is preferred for the stricted environments is therefore to innovate most vulnerable infants, such as very low birthweight infants and those with postnatal growth strategies of maximizing nutrition from avail- failure able/affordable milk products. The innovations R Vitamins and iron should be supplemented espe- must be undertaken while minimizing the risk of cially in those on unfortified breast milk or stan- feed intolerance, necrotizing enterocolitis [5] , dard formula Copyright © 2008 S. Karger AG, Basel and overload-related cardiac complications [6] . The suggested strategies include: maximal utilization of PM, pooling PM to be used by older infants, use of larger volumes ( 1 240 ml/kg/day) Introduction after 14–28 days, selective breast milk fortification and deliberate supplementation of mother’s Preterm and low birthweight infants have higher milk with PTF [7, 8] . nutritional needs than their more mature and This chapter reviews the use of crystalloids larger counterparts. Quantitative analysis indi- during the acute phase, the rapid transition from cates that such infants need intakes of 3.6–4 g crystalloids to milk, the optimizing of full enter- and as much as 120 kcal/kg/day to achieve ade- al feeding, and the addition of some essential mi- quate growth if fed enterally [1] . In countries cronutrients as innovations to use when under- with restricted health budgets, these require- funded. Table 1. Required volumes of milk needed to provide 4 g/kg of Type of milk Birthweight category protein and the nutritional value <1.0 kg 1.0–1.5 kg 1.5–2 kg of available milk preparations BM, 1st 28 days 220 200 180 BM, >28 days/standard formula 400 390 360 PTF 170–200 160–200 150–180 Fortified BM 200 200 180 1:1 PTF and BM >28 days 280–300 230–260 200–240 1:1 BM and donor PM 300 260 240

Food value of milk, per 100 ml Protein, g Energy, kcal

Term BM 0.9 60–75 Preterm BM 1.9 70–75 PTF 2.0–2.4 80–85 Fortified BM 2.0 74–93 1:1 PTF and BM 1.5–1.7 70–80 1:1 BM and donor PM 1.5 70–75

Daily requirements of micronutrients

Vitamin A 450 ␮g/kg Vitamin C 10 mg/kg Vitamin D 400 IU Vitamin E 1 mg/kg Vitamin B1 0.5 g/kg Vitamin B2 0.5 g/kg Vitamin B6 0.015 mg/g of protein Iron 5 mg/kg of elemental iron Folate 50 ␮g/kg BM = Breast milk; PM = breast milk from mothers who delivered prema- 3 turely; PTF = preterm formula.

Initial Crystalloids Enteral Feeds

Many small infants develop early complications Initiation making immediate enteral feeding hazardous. It is possible for even the smallest or the sickest Even healthy babies may not tolerate enteral feeds infants to be safely fed enterally if the primary immediately after birth. Intravenous crystalloids condition is stable. Healthy infants can feed on are often required to support circulation, blood day 1 while sick ones start from days 2–4 (fig. 1). sugar and electrolytes as summarized in table 2 Though necrotizing enterocolitis has been asso- during this period. During this phase, infants ciated with enteral feeding [10] , there is no con- can receive small feed volumes (trophic feeds) to clusive evidence that early feeding adds to the stimulate their gut [9] . risk. Full feeds should therefore be achieved by day 5–10 in most infants.

Feeding the Low Birthweight Infant in a Resource-Restricted Environment 205 1st 1–4 h Stabilize the baby Warmth, oxygen

Baby stable Baby not stable

Bwt <1.0 kg Bwt 1–1.5 kg Bwt >1.5 kg Bwt <1.0 kg Bwt 1–1.5 kg Bwt >1.5 kg IV fluids alone for IV fluids and Full enteral feeds IV fluids alone for IV fluids for IV fluids and 1st 24 h enteral feeds 24–72 h 24 h milk feeds

Feed from day 2 Full feeds by Breastfeed Trophic feeds Nutritional Full feeds Full feed day 7 day 3–5 when suck from day 2 feed day 2 days 3–7 Vitamins day 8 Vitamins day 8 reﬂex strong Nutritional day 4

Iron and folate Iron and folate Vitamins and Full feeds Full feeds Breastfeed 6 weeks or when 6 weeks or when iron day 10 day 7 when suck Bwt doubles Bwt doubles optional Vitamins day 11 Vitamins day 8 reﬂex strong

Iron and folate Iron and folate Vitamins and 6 weeks or when 6 weeks or when iron Bwt doubles Bwt doubles optional

Fig. 1. Algorithm for the timing of enteral feeds for the low birthweight/preterm infant. Bwt = Birthweight; IV = intravenous.

Table 2. Administration of crystalloids

Birthweight Daily fluid intake, ml/kg kg day 1 day 2 day 3 day 4 day 5 day 6 day 7

≤1.0 100 120 140 160 180 200 200 1.0–1.5 80 100 120 140 160 180 180 >1.5 60 80 100 120 140 150 150 Type of crystalloid 10% dextrose 10% dextrose with 2–3 mmol/kg/day of sodium and potassium, or mixture of Darrow’s, Hartman’s or Ringer’s at 4:1 ratio with 50% dextrose

Breast Milk from 1.1 to 3.5 (median of 1.9) g/100 ml [2] . Dur- The breast milk of mothers in advanced lactation ing the first 14 days, infants can therefore grow on has a nutritional value of 0.9 g protein and 60–70 220, 200 and 180 ml/kg/day if weighing ! 1.0, kcal/100 ml (table 1). During the first 14–28 days, 1.0–1.5 and 1 1.5 kg, respectively. Thereafter, in- however, mothers who deliver prematurely pro- fants weighing ! 1.5 kg will require up to 400 ml/ duce milk (PM) with a protein content ranging kg of their mothers’ milk for adequate nutrition.

206 Pediatric Nutrition in Practice Such large volumes are unlikely to be tolerated in M i c r o n u t r i e n t s practice and may even overload the infants with lipids and other nutrients. In the absence of forti- The daily requirements of micronutrients includ- fication the highest tolerated volume should be ing vitamins and iron ( table 1 ) should be given to tried even in the smallest infants. This may suc- all very low birthweight infants as recommended ceed with smaller aliquots given every 1 or 2 h for [10] and indicated in figure 1 . babies weighing ! 1.0 and 1.0–1.5 kg. Donor PM at a 1: 1 ratio with own mother’s milk will also allow the use of lower volumes (280–300 ml/kg/day). Conclusions The preferential use of donor PM keeps the volumes at pre-day-14 levels. The HIV status of do- • In the absence of total parenteral nutrition, nors must be known to exclude the risks of HIV enteral feeds should be started on day 1 for all transmission. stable babies and not delayed beyond day 4 for even the sickest infants Breast Milk Fortification and Preterm Formula • The best milk strategy available should always Where available, this option makes it possible to be preferred. Larger volumes of nutritionally provide the requirements for most small babies poorer milk should be adopted as tolerated. with the traditional 180–200 ml/kg/day (table 1). Milk pooled from mothers who delivered pre- If only limited financial reserves are available for maturely offers an option to cut down on vol- selective fortification or PTF, then infants weigh- umes ing !1.5 kg or those who either fail to grow well • With a smaller budget, breast milk fortifica- on the large volumes of mothers’ milk recom- tion and/or preterm formula can be used for mended above or develop volume-related intoler- special groups such as very low birthweight ance can benefit from the technology. infants and those with poor growth on maxi-

As has been reported [7, 8] , deliberate 1: 1 mix- mal volumes of standard milk ing of PTF with breast milk reduces the volume • Vitamins and iron should be provided to all required for better growth (table 1). The required infants born weighing less than 1.5 kg 3 volumes for different types of milk are summarized in table 1 .

References

1 Ziegler EE, Thureen PJ, Carlson SJ: 4 Schanler RJ, Shulman RJ, Lau C: Feed- in preterm infants feed on expressed Aggressive nutrition of the very low ing strategies for premature infants: milk, a preterm infant formula, and

birthweight infant. Clin Perinatol 2002; beneficial outcomes of feeding fortified two low-salute adapted formulae. Arch

29: 225–244. human milk versus preterm formula. Dis Child 1982; 57: 898–904.

2 Weber A, Loui A, Jochum F, et al: Pediatrics 1999; 103: 1150–1157. 8 Were FN, Bwibo NO: Early growth of Breast-milk from mothers of very low 5 Goldman HI: Feeding and necrotizing very low birth weight infants. East Afr

birthweight infants: variability in fat enterocolitis. Am J Dis Child 1980; 134: Med J 2006; 83: 84–89. and protein content. Acta Paediatr 553–555. 9 Tyson JA, Kennedy KA: Trophic feed-

2001; 90: 772–775. 6 Bell E, Warburton D, Stonestreet BS, ings for parenterally fed infants.

3 Moro GE, Minoli I: Fortification of hu- Oh W: Effect of fluid administration on Cochrane Database Syst Rev 2005; 3: man milk; in Ziegler EE (ed): Nutrition the development of patent ductus arte- CD000504. of the Very Low Birthweight Infant. riosus and congestive heart failure in 10 Nutrition Committee, Canadian Paedi-

Nestlé Nutr Workshop Ser Pediatr Pro- premature infants. N Engl J Med 1980; atric Society: Nutrient needs and feed-

gram. Philadelphia, Lippincott Wil- 302: 598–604. ing of premature infants. CMAJ 1985;

liams & Wilkins, 1999, vol 43, pp 81– 7 Brooke OG, Wood C, Barley J: Energy 152: 1765–1785. 93. balance, nitrogen balance, and growth

Feeding the Low Birthweight Infant in a Resource-Restricted Environment 207 Koletzko B. (ed): Pediatric Nutrition in Practice. Basel, Karger, 2008, pp 208–213

3 Nutritional Challenges in Special Conditions and Diseases

3.15 Diabetes Mellitus and Inborn Errors of Metabolism Hansjosef Böhles

Key Words olites. This review addreses phenylketonuria (ac- Diabetes mellitus type 1 ؒ Phenylketonuria ؒ cumulation of phenylalanine), maple syrup urine Maple syrup urine disease ؒ Urea cycle disorders disease (accumulation of leucine) and urea cycle disorders (accumulation of ammonia, NH 3). Disorders requiring glucose stabilization are Key Messages those threatening hypoglycemia and can patho- R Disorders requiring anabolism and avoidance of physiologically be reduced to disturbances of gly- toxic metabolites: phenylketonuria, organic acid- cogen degradation and gluconeogenesis. The lat- urias, maple syrup urine disease, urea cycle disor- ter can be described as having a defect of gluco- ders neogenetic enzymes and with an insufficient R Disorders requiring glucose stabilization: fatty acid oxidation defects, sugar intolerances, glycogen energy supply for gluconeogenesis (fatty acid ox- storage diseases, gluconeogenesis defects idation defect). R Disorders requiring restriction of energy turn- Disorders requiring the restriction of energy over: pyruvate dehydrogenase deficiency, elec- turnover (glucose to avoid lactic acidosis) are de- tron transport chain defects fects located in the mitochondria (mitochondri- Copyright © 2008 S. Karger AG, Basel opathies) and mainly comprise pyruvate dehydrogenase (PDH) deficiency and disorders of the respiratory chain. Introduction

Diabetes mellitus type 1 is the most frequent Diabetic Ketoacidosis endocrinological disturbance of childhood. It amounts to 5–10% of the total diabetic popula- Rehydration tion. In more than 95% of affected children it is In most cases of diabetic ketoacidosis dehydra- an autoimmunological disease. The aim of ther- tion amounts to about 10%. To stabilize the cir- apy is a near normal serum glucose concentra- culatory volume, half of the calculated fluid re- tion and the avoidance of hypoglycemia and ke- quirement should be administered within the toacidosis, in order to minimize the risk of dia- first 8 h and the second half in the following 16 h. betic angiopathy. However, as we are dealing with a hypertonic de- Disorders requiring anabolism and preven- hydration despite a low serum sodium concen- tion of protein degradation represent a threat tration, serum osmolality should be lowered not with respect to the accumulation of toxic metab- faster than 4 mosm/l per hour. For rehydration 0.9% NaCl solution or Ringer-lactate solution is 50% of the calories should be consumed as carbo- adequate. When the serum glucose concentra- hydrates with a low glycemic index. tion is lowered to ϳ 250 mg/dl ( ϳ 14 mmol/l) If a conventional insulin therapy (2–3 injec- the infusion should contain glucose (i.e. 0.9% tions/day with a mixture of rapid and intermedi-

NaCl:5% glucose = 1: 1) to avoid the risk of drop- ate acting insulin) is performed, e.g. in the toddler ping into hypoglycemia. In conscious patients, age group, a strictly regulated and disciplined di- rehydration can be assisted by oral fluid intake. etary intake should be followed. The dietary intake should be harmonized with physical activity Insulin Supplementation and the amount of insulin injected. Normally the Continuous intravenous infusion of about 0.05 required amount of insulin is ϳ0.8–1.0 IU/kg per IU regular (short-acting) insulin/kg per hour. day. In teenagers an intensified insulin treatment The amount of insulin is adapted after hourly (6 4 injections/day supplying basal insulin, meal controls of the serum glucose concentration. insulin in doses proportional to nutritional load, and extra insulin when needed to correct high Anti-Acidosis Treatment glucose levels) allows a sufficiently liberal food in- Because rehydration is the most effective form of take, adapted to the needs of daily life. anti-acidotic treatment, only in extremely severe cases (pH 7.0 or below; HCO3 ! 5 mmol) should a slight buffering with NaHCO 3 be considered. Ag- Disorders Requiring Anabolism and gressive buffering may result in paradoxic acido- Avoidance of the Accumulation of Toxic sis of the cerebrospinal fluid with ensuing loss of Metabolites consciousness. Phenylketonuria Electrolyte Supplementation Deficient activity of phenylalanine hydroxylase In diabetic ketoacidosis the following deficits can (1 400 mutations known) leads to a markedly in- usually be assumed: sodium 5–6 mmol/kg, chlo- creased serum phenylalanine (Phe) concentra- ride 3–5 mmol/kg, and potassium 3–6 mmol/kg. tion, while tyrosine is normal or decreased. The 3 ϳ The serum potassium concentration should be prevalence in central Europe is 1: 10,000, in ϳ monitored closely because effective treatment of Turkey and Ireland 1: 5,000. Early treatment, diabetic ketoacidosis tends to induce pronounced starting in the neonatal period, allows normal hypokalemia. psychomotor development of the child. The principle of dietary treatment is a restricted protein intake to the amount needed for pro- Dietetics of Diabetes Mellitus Type 1 tein synthesis, with concomitant supplementation of a Phe-free amino acid preparation to cov- Dietetic Treatment of Diabetes Mellitus Type 1 er the total protein requirements, aiming at a There is no need to use any of the commercially plasma Phe concentration of 0.7–4 mg/dl (42–240 available special diabetic food products. Qualita- ␮ mol/l) up to 10 years and 0.7–15 mg/dl (42–900 tively valuable, mainly homemade foods may be ␮ mol/l) up to 16 years. Because of the rapid used. Carbohydrates should be classified accord- growth of infants and young toddlers, more Phe ing to their glycemic index. A trend towards a per kilogram bodyweight is tolerated in this age mainly vegetarian diet should be encouraged, but group than in older children. The need for addi- in this case attention needs to be paid to iron, cal- tional tyrosine intake is covered by commercial cium, vitamin D and vitamin B12 intakes. Ideally Phe-free protein supplements.

Diabetes Mellitus and Inborn Errors of Metabolism 209 Table 1. Recommended phenylalanine intake in pa- leucine metabolite 2-keto-3-methylvaleric acid tients with phenylketonuria causes the characteristic maple syrup smell. The Age, months Phenylalanine, mg/kg per day forms of manifestation are: severe in the first days of life, mild intermittent form, and the thia- 6 34 (27–41) mine responsive form. In mild forms, the first 12 28 (21–35) symptoms may manifest as late as in adulthood. 18 26 (20–32) The treatment principles at manifestation 24 23 (18–28) 30 22 (17–27) are: 36 20 (15–25) (1) Stop protein administration to avoid accumu- 42 19 (14–24) lation of toxic ketoacids 48 18 (13–23) (2) Forced diuresis (furosemide 0.5–1 mg/kg ev- 54 17 (12–23) 60 17 (12–23) ery 6–12 h) up to hemofiltration for the elimi- 66 16 (12–20) nation of ketoacids 72 15 (10–20) (3) Buffer therapy of acidosis (4) Intravenous glucose 10–20 g/kg per day; if needed + insulin (0.01–0.5 IU/kg per hour). Insulin additionally stimulates the uptake of The Phe requirement in the first year of life is branched chain amino acids into muscle cells about 30–50 mg/kg per day. Starting in the 3rd (5) Thiamine (5–10 mg/day) year of life this requirement is about 10–20 mg/kg (6) Energy supply ( 1100 kcal/kg per day), includ- per day (table 1 ) [1] . ing calories from fat (e.g. 0.5–1 g/kg per day Affected infants may be partially breastfed: i.v.) first a predetermined amount of the Phe-free Long-term treatment principles are similar as preparation is given, followed by feeding at the in phenylketonuria: restriction of the protein in- mother’s breast. The amount of breast milk toler- take to reduce the uptake of leucine, isoleucine ated will usually be about half the amount taken and valine. Rapidly growing children have a by a healthy infant. higher tolerance of the branched chain amino ac- The diet should be continued for life; however, ids ( table 2 ) [2] . The total protein requirement is after puberty serum Phe concentrations up to 20 covered with commercially available amino acid mg/dl (1,200 ␮ mol/l) are tolerated. mixtures free of branched chain amino acids. Breast milk has very low leucine concentra- Maternal Phenylketonuria tions and should therefore be used preferentially. Adult women with phenylketonuria wishing to As in phenylketonuria the affected infant re- become pregnant must lower their serum Phe ceives about half the amount of milk as a leucine- concentration to ! 4 mg/dl (240 ␮ mol/l) already isoleucine-valine-free formula, and the other half before conception to prevent congenital heart de- as breast milk. Food products used after the fects, microcephaly and mental retardation in the breastfeeding period are selected according to child. With ongoing pregnancy Phe tolerance in- nutritional tables. creases. Tyrosine must be supplemented. Organic acidemias, such as propionic acidemia, methylmalonic acidemia, and isovaleric aci- Maple Syrup Urine Disease demia, present in a similar way and the treatment Maple syrup urine disease is caused by a decar- principles correspond to those mentioned above. boxylation defect of the branched chain amino With the accumulation of high amounts of acti- acids (leucine, isoleucine and valine). The iso- vated organic acids (Acyl-CoAs) the carnitine

210 Pediatric Nutrition in Practice Table 2. Leucine, isoleucine and valine requirements of Table 3. Protein supply in patients with urea cycle de- patients with maple syrup urine disease fects

Age Leucine Isoleucine Valine Age Natural Mixture of mg/kg mg/kg mg/kg group protein essential amino acids1 per day per day per day g/kg per day g/kg per day

0–6 months 100–60 90–30 95–40 Infants 0.5–1.3 0.3–0.6 6–12 months 75–40 90–30 60–30 Toddlers 0.5–1.0 0.3–0.5 1–4 years 70–40 85–20 85–30 Schoolchildren 0.5–1.0 0.2–0.3 4–7 years 65–35 80–20 50–30 7–11 years 60–30 30–20 30–25 1 0.6 g essential amino acids correspond to 1 g protein 11–15 years 50–30 30–20 30–20 equivalent. 15–19 years 40–15 30–10 30–15

requirements are increased, and patients are kg in 10% glucose (NH 3 elimination as N in supplemented with about 100 mg L -carnitine/kg hippuric acid). During phenylbutyrate thera- per day. py the plasma concentrations of the branched chain amino acids must be watched (6) Arginine hydrochloride 210 mg (1 mmol)/kg Urea Cycle Defects in 10% glucose

The enzymatic defects of the urea cycle are local- Principles of Long-Term Treatment ized both in- and outside the mitochondria. Their Protein restriction should be carried out in com- characteristic symptom is protein intolerance bination with points 5 and 6 above. Protein deg- with hyperammonemia, leading to severe en- radation should be minimized by provision of an cephalopathy. In severe forms the acid-base ho- adequate energy intake. For optimal growth the meostasis is altered towards alkalosis. Ammonia provision of a supplement with essential amino 3 detoxification via glutamate and glutamine for- acids is needed to direct surplus N into protein mation leads to an energy deficit via the depletion synthesis (table 3) [3] . This mixture should be of citric acid cycle metabolites. This is thought to rich in branched chain amino acids and poor in be the cause of brain edema. tryptophan (high tryptophan concentrations lead to a lack of appetite). The administration of Treatment Principles at Manifestation arginine is essential because it is not sufficiently Plasma ammonia concentrations of 1 200 ␮ mol/l formed during inadequate urea synthesis. (340 ␮ g/dl) require emergency treatment: (1) Stop protein intake (2) Intravenous glucose and lipids in amounts to Disorders Requiring Glucose Stabilization support anabolism (3) Forced diuresis Medium-Chain Acyl-CoA Dehydrogenase (4) Hemodialysis at plasma ammonia concentra- Deficiency tions of 1 400 ␮ mol/l (680 ␮ g/dl) Medium-chain acyl-CoA dehydrogenase defi- (5) Sodium phenylbutyrate 250 mg/kg in 10% ciency is the most frequent fatty acid oxidation glucose (NH 3 elimination as N in phenyl- defect presenting clinically after a fasting period acetylglutamine) or sodium benzoate 250 mg/ of some hours or during minor infections and

Diabetes Mellitus and Inborn Errors of Metabolism 211 physical stress with lethargy, vomiting, seizures not possible. Serum glucose concentrations are (Reye-like symptoms). therefore dependent on the intake of free glucose. Treatment principles: avoidance of fasting pe- Fasting tolerance is only about 2 h before hypo- riods; provide an adequate glucose supply using glycemia occurs. complex carbohydrates, mainly during the night; Treatment principles: Frequent carbohydrate- uncooked cornstarch may be useful; 50–100 mg containing meals during the day, and continuous L -carnitine/kg per day. glucose intake during the sleeping hours in the night by a nasogastric glucose infusion (10 mg/kg per min) is recommended. Oligosaccharide-con- Sugar Intolerances taining solutions can be used. Starting in the toddler age group uncooked cornstarch (ϳ 2.5 g/kg) Galactosemia (Galactose-1- can be used to reach a fasting tolerance of up to Phosphateuridyltransferase Deficiency) 7 h. The slow glucose release is only preserved As galactose is present in breast milk as well as when cornstarch is not heated or mixed with car- in most infant formulas, the clinical symptoms bonate-containing drinks. A slow glucose release (vomiting, jaundice, liver function problems can also be obtained when, e.g., rice is only cooked leading to disturbed blood coagulation and bleed- for 4 min. ing disorders) appear with the onset of milk feeding which is usually immediately after birth. Defects of Gluconeogenesis Treatment principles: Avoidance of lactose and Deficiencies of pyruvate carboxylase, phospho- galactose intake. The long-term outcome is dis- enolpyruvate carboxykinase, fructose-1,6-di- appointing because endogenous galactose pro- phosphatase, glucose-6-phosphatase = GSD-1. duction during cell turnover (up to ϳ 2 g/day) As gluconeogenesis is active when the liver glyco- cannot be stopped. gen stores are depleted, the treatment principle is to supply glucose as early as possible so that glu- Hereditary Fructose Intolerance coneogenesis is not needed. However GSD-1 has (Fructose-1-Phosphatealdolase Deficiency) to be considered separately (see above). The clinical symptoms appear with the first fructose exposure, which depends on the way of feeding and may be at any time during the first year Disorders Requiring Restriction of Energy of life (symptoms like in galactosemia). Turnover Treatment principles: Elimination of fructose, sucrose and sorbitol from the diet. A high degree Pyruvate Dehydrogenase Defect, Citric Acid of suspicion with regard to industrial food prod- Cycle Defects, Electron Transport Chain Defects ucts (which often contain fructose) has to be de- (Mitochondrial Defects) veloped. Patients generally develop a strong aver- NADH is produced especially during glucose sion to sweet taste, therefore an unintentional degradation. Hydrogen processing in the mito- fructose intake is rare. chondria finally leads to ATP formation. A disturbance in the metabolic steps of hydrogen pro- Glycogen Storage Defect 1 cessing always leads to a backing up of NADH (Glucose-6-Phosphatase Deficiency) and thus to lactic acid formation. In glycogen storage defect 1 (GSD-1) the genera- Treatment principles: Reduction of glucose ad- tion of free glucose is not feasible, and glucose ministration to reduce lactic acidosis. The nutri- formation from galactose, fructose or protein is tional basis of treatment is a ‘ketogenic diet’ with

212 Pediatric Nutrition in Practice emphasis on fat and protein intake. Vitamin B 1 Maple Syrup Urine Disease (thiamine pyrophosphate) and lipoic acid are the • Branched chain amino acid-free amino acid coenzymes of PDH and should be supplemented mixture; add isoleucine and valine at abnor- in PDH deficiency. In cases of respiratory chain mal leucine concentrations defects a cocktail of ‘artificial electron acceptors’ can be tried. Organic Acidemias • Most require L -carnitine (100 mg/kg per day)

C o n c l u s i o n s Medium Chain Acyl-CoA Dehydrogenase Deficiency D i a b e t e s • Avoid fasting periods, especially during mi- • No special dietetic food products are neces- nor infections and physical stress sary • 50% of the calories as low glycemic index car- Galactosemia bohydrates • Avoid dietary lactose/galactose

Phenylketonuria Hereditary Fructose Intolerance • Infants can be partially breastfed • Avoid dietary fructose, sucrose, sorbitol and • The lifelong diet provides limited amounts of honey natural protein (determined by phenylalanine tolerance) plus a phenylalanine-free amino Glycogen Storage Defect 1 acid mixture to meet calculated protein re- • Galactose, fructose and protein cannot be quirements used as sources for glucose • Female patients desiring pregnancy must • Frequent supply of glucose/glucose polymers limit serum phenylalanine to ! 4 mg/dl (242 ␮ mol/l) to prevent fetal damage 3

References

1 Wendel U, Ullrich K, Schmidt H, 2 Elsas LJ, Acosta PB: Nutritional support 3 Müller E: Harnstoffzyklusstörungen; Batzler U: Six-year follow up of phenyl- of inherited metabolic disease; in Shils in Müller E (ed): Praktische Diätetik in alanine intakes and plasma phenyl- ME, Olson JA, Shike M, Ross AC (eds): der Pädiatrie. Grundlagen für die alanine concentrations. Eur J Pediatr Modern Nutrition in Health and Dis- Ernährungstherapie. Heilbronn, SPS

1990; 149(suppl 1):S13–S16. ease, ed 9. Philadelphia, Lea & Febiger, Verlag, 2003, p 89. 1999, p 1003.

Diabetes Mellitus and Inborn Errors of Metabolism 213 Koletzko B. (ed): Pediatric Nutrition in Practice. Basel, Karger, 2008, pp 214–218

3 Nutritional Challenges in Special Conditions and Diseases

3.16 Hypercholesterolemia Berthold Koletzko

Key Words as coronary heart disease and stroke, and for the ,Hypercholesterolemia, familial ؒ Low-density associated increased mortality [1, 2]. In children lipoprotein cholesterol ؒ Dietary treatment ؒ high plasma cholesterol and LDL cholesterol lead -Fat, saturated ؒ Plant sterols to enhanced early development of vascular dam age in autopsy studies, and clinical studies using ultrasound techniques show increased lipid de- Key Messages position in the vascular intima and decreased R Children with severe hypercholesterolemia should vascular distensibility. For the general popula- be diagnosed and treated early to reduce the risk tion, including children, healthy lifestyles and di- for premature cardiovascular morbidity and mor- etary habits that promote cardiovascular health tality R Dietary modification can be initiated from the age are advocated [2, 3] . Children with markedly el- of 2–3 years onwards evated cholesterol, for example due to primary R Modifying dietary fat intake with limitation of satu- genetic disorders such as familial hypercholester- rated fats and their replacement by monounsatu- olemia, should be diagnosed early and treated ef- rated and polyunsaturated fats are the most im- fectively. The basis of intervention in children portant factors R Preferential consumption of complex and slowly with hypercholesterolemia is dietary modifica- digested carbohydrates over sugars moderately tion, as described here. In selected children who reduces plasma cholesterol levels but is often dif- do not achieve a satisfactory reduction in plasma ficult to achieve in children cholesterol concentrations with diet alone, the R Soluble (but not insoluble) dietary fiber may con- use of lipid-lowering drugs in addition to diet tribute to cholesterol lowering and may be recom- should be considered. mended to selected, highly motivated families Copyright © 2008 S. Karger AG, Basel

Lipoproteins

Introduction Lipids are transported in the plasma by lipoproteins ( table 1 ), which carry apoproteins that medi- A large body of evidence from epidemiological ate their receptor binding and tissue uptake. Tri- and intervention studies in adults demonstrates glyceride-rich chylomicrons are formed in intes- that high plasma concentrations of cholesterol tinal epithelial cells with absorbed dietary fats, and particularly of low-density lipoprotein (LDL) are secreted into the lymph and consecutively cholesterol are risk factors for the early develop- transported into the blood stream. Chylomicron ment of premature cardiovascular diseases such triglycerides are hydrolyzed by lipoprotein lipase Table 1. Characteristics of plasma lipoproteins

Chylomicrons VLDL LDL HDL

Major lipids Triglycerides Triglycerides Cholesterol Cholesterol, phospholipids Major apoproteins A, B48, C B100, C, E B100 A, E Formation Gut Gut, Liver VLDL catabolism Gut, Liver Major function Transport of exogenous Transport of endogenous Cholesterol transport Cholesterol transport triglycerides triglycerides from the liver to extrahepatic tissues from extrahepatic to extrahepatic tissues tissues to the liver

VLDL = Very low-density lipoprotein; LDL = low-density lipoprotein; HDL = high-density lipoprotein.

linked to the capillary endothelium. Lipolysis Table 2. Cholesterol levels considered desirable, bor- products are taken up and utilized by tissues. Li- derline and undesirable in children and adolescents poprotein lipase also hydrolyzes triglycerides in (<20 years) by the United States National Cholesterol Ed- ucation Program [3] very low-density lipoproteins (VLDLs) synthe- sized in the gut and liver. This lipolysis results in Desirable Borderline Undesirable formation of intermediate-density lipoproteins level, mg/dl level, mg/dl level, mg/dl and further of LDL in the circulation. LDLs are Total cholesterol <170 170–199 ≥200 rich in cholesterol and apoprotein B100, bind to LDL cholesterol <110 110–129 ≥130 apoprotein receptors in hepatocytes and periph- HDL cholesterol >45 35–45 <35 eral cells, and transport cholesterol to tissues. Triglycerides <125 – ≥125 High plasma concentrations of LDLs lead to in- LDL = Low-density lipoprotein; HDL = high-density li- creased deposition of cholesterol in the vascular poprotein. To convert values expressed in mg/dl into intima, atherosclerotic vascular damage and pre- mmol/l multiply by 0.0259 (cholesterol) or 0.0113 (trig- 3 mature coronary artery disease. LDL cholesterol lycerides). can be measured directly by using ultracentrifu- gation, but in clinical practice is usually determined after an overnight fast using the Friede- wald formula: LDL cholesterol (mg/dl) = total of HDL are protective against the development of cholesterol (mg/dl) – HDL cholesterol (mg/dl) – atherosclerotic diseases. While reference values [triglycerides (mg/dl) ! 0.2]. (To convert choles- for cholesterol differ among various populations terol in mg/dl into mmol/l multiply by 0.0259.) In- and geographic locations, levels considered desir- creased plasma levels (1 30 mg/dl) of lipoprotein able in children in the USA are shown in table 2 . (a), an LDL particle with added apoprotein (a), are an independent risk factor for coronary artery disease and juvenile thrombosis. The liver and Hypercholesterolemia gut secrete apoprotein A containing high-density lipoprotein (HDL) low in cholesterol (‘nascent The heterozygous form of familial hypercholes- HDL’), which takes up cholesterol from tissues terolemia is one of the most frequent inherited and from VLDL and LDL and transports it back metabolic disorders, affecting about 1 in 500 new- to the liver. In contrast to LDL, high plasma levels borns in Europe and North America. The under-

Hypercholesterolemia 215 Table 3. Selected secondary hyperlipidemias in children LDL apheresis or liver transplantation. A pheno- and adolescents type similar to the heterozygous form of familial Hypercholesterolemias hypercholesterolemia is found in children with Acute intermittent porphyria familial defective apoprotein B also leading to de- Anorexia nervosa fective receptor binding or LDL. Its prevalence is Cholestatic liver diseases almost as high as the LDL receptor defect. Sec- Cushing syndrome ondary hyperlipidemias (table 3) are not rare in Hypothyreosis Nephrotic syndrome, renal failure, dialysis children and can often be influenced by treating the underlying disorder or by elimination of caus- Hypertriglyceridemias Obesity ative substances. Severe and lasting secondary Diabetes mellitus hyperlipidemias may necessitate treatment simi- Glycogen storage disease type 1 lar to primary genetic hyperlipidemias. Pancreatitis Combined hyperlipidemias Obesity Dietary Treatment of Hypercholesterolemia Diabetes mellitus Glycogen storage disease type 1 Hepatitis Treatment should achieve a lasting lowering of Nephrotic syndrome, renal failure, dialysis cholesterol, thereby reducing the risk of prema- Drugs: ␤-blockers, corticoids, estrogens, progesterone, ture cardiovascular morbidity and mortality, thiazide diuretics while supporting a good quality of life and enjoy- Pregnancy 1 Systemic lupus erythematodes ment of eating, at normal HDL cholesterol ( 45 mg/dl). Dietary modification should be considered at LDL cholesterol 1130 mg/dl [4] (table 2). Prerequisites for an effective dietary change are lying defect in LDL receptor function is domi- good information and motivation of patient and nantly inherited (i.e. affects ; 50% of children of family, which should be supported by repeated an affected parent). From the onset of enteral counseling and practical training. feeding, levels are markedly increased for LDL Dietary modification can be initiated from cholesterol (usually 1 180 mg/dl), total cholesterol the age of 2–3 years onwards [3] . Modifying di- ( 1250 mg/dl) and apoprotein B ( 1150 mg/dl; etary fat intake is the most important factor. Sat- Frederickson hyperlipidemia type IIa). In un- urated fatty acids with 12–16 carbon atoms (pri- treated patients, coronary heart disease may oc- marily animal fats and some tropical oils) and cur already at middle age. Diagnosis is based on trans-isomeric fatty acids (primarily from hydro- repeated measurement of plasma lipoproteins in genated fats) increase LDL cholesterol ( table 4 ) the fasted state and family history (dominant in- and should not exceed 8–12% of the dietary en- heritance), and if desired by molecular genetics. ergy intake. Dietary fat should preferentially The rare homozygous form of familial hypercho- comprise monounsaturated fatty acids (1 10% of lesterolemia is found in 1 in 1,000,000 individuals energy; primarily rapeseed and olive oils), which and leads to excessive levels of cholesterol (1 600 reduce LDL and increase HDL cholesterol ( ta- mg/dl) from infancy due to practically complete ble 4 ), and moderate amounts of polyunsaturated deficiency of LDL receptor function. Affected fatty acids (7–10% of energy; e.g. corn and sun- children develop xanthomas already in the first flower seed oils). Limiting the total fat intake to decade of life and usually die before the age of 20 30–35% of energy intake contributes to the de- years unless effectively treated by extracorporeal sired limitation of saturated and trans-fatty acid

216 Pediatric Nutrition in Practice Table 4. Effects of dietary fats on plasma LDL and HDL cholesterol

Dietary fats Food sources Cholesterol LDL HDL

Saturated fatty acid (12–16 carbons) Fatty milk products (butter, cream), fatty meats, coconut oil d d d d Trans-fatty acids Hydrogenated fats (deep frying fats, hard margarine, d d f baked goods); ruminant fats (milk, beef, lamb) Monounsaturated fatty acids Rapeseed and olive oil, avocado f f d (e.g. oleic acid) Polyunsaturated fatty acids Most vegetable oils (e.g. corn oil, sunflower seed oil), f ff (at high (e.g. linoleic acid) soft margarine intakes) Cholesterol Eggs, offal d =

LDL = Low-density lipoprotein; HDL = high-density lipoprotein.

intake. Dietary cholesterol intake should be !300 population) with higher mean cholesterol and mg/day [1–3] . lower triglyceride levels show a stronger response Preferential consumption of complex and slow- of plasma cholesterol to dietary cholesterol in- ly digested carbohydrates over sugars (mono- and take. In contrast, individuals with apoprotein E3 disaccharides) moderately reduces plasma choles- (; 75–80% of the population) show a lesser re- terol levels. Soluble dietary fiber (e.g. parts of oat sponse to dietary cholesterol restriction. bran, psyllium) may also contribute to cholesterol The regular consumption of plant sterols or lowering, but not insoluble fiber (e. g. wheat bran) plant stanols from enriched spreads or other en- [5] . However, diets with strictly limited sugar and riched foods (also available as granulates) can 3 high fiber content are difficult to maintain for markedly reduce plasma LDL cholesterol by an many children and should only be recommended additional 10–15% [7] and is encouraged. for selected, highly motivated families. If dietary modification alone does not achieve Patients and their family members require in- a satisfactory reduction in plasma LDL, addition- tensive dietary counseling by a physician and a al drug treatment with statins, ezetimibe or an- dietician or nutritionist. Concomitant to dietary ion exchange resins may be considered from the treatment, normal weight and regular physical age of about 10 years onwards [8] , but diet should activity are encouraged and smoking is strongly be continued. discouraged. Dietary records may indicate existing problems and help achieve improvements. The effect of treatment is assessed by repeated Conclusions measurements of LDL cholesterol (every ;3–6 months). Dietary fat modification may reduce • At normal HDL cholesterol (1 45 mg/dl), di- LDL on average by 10–15% [6] , with marked in- etary modification should be considered in ter-individual variation partly predicted by the children with LDL cholesterol 1130 mg/dl apoprotein E genotype: individuals with the apo- • Dietary saturated and trans-fats should be protein E4 phenotype ( ; 10–15% of the European limited to 8–12% of energy intake (E%), while

Hypercholesterolemia 217 monounsaturated fats should provide 1 10 E% • This dietary fat modification may reduce LDL and polyunsaturated fats 7–10 E% by 10–15%, with marked inter-individual • Limiting the total fat intake to 30–35% of en- variation ergy intake contributes to the desired limita- • Regular consumption of plant sterols/stanols tion of saturated and trans-fatty acid intake from enriched foods can reduce plasma LDL • Dietary cholesterol intake should be ! 300 cholesterol by an additional 10–15% mg/day • Dietary treatment should be continued if drugs are used

References

1 Graham I, Atar D, Borch-Johnsen K, 2 Kavey RE, Allada V, Daniels SR, Hay- 4 National Cholesterol Education Pro- Boysen G, Burell G, Cifkova R, Dallon- man LL, McCrindle BW, Newburger gram Coordinating Committee: Report geville J, De Backer G, Ebrahim S, JW, Parekh RS, Steinberger J; American of the Expert Panel on Blood Choles- Gjelsvik B, Herrmann-Lingen C, Hoes Heart Association Expert Panel on terol in Children and Adolescents. NIH A, Humphries S, Knapton M, Perk J, Population and Prevention Science; Publication No. 91-2732. Bethesda, Na- Priori SG, Pyorala K, Reiner Z, Ruilope American Heart Association Council tional Heart, Lung and Blood Institute, L, Sans-Menendez S, Op Reimer WS, on Cardiovascular Disease in the 1991. Weissberg P, Wood D, Yarnell J, Zamo- Young; American Heart Association 5 Aggett PJ, Agostoni C, Axelsson I, Ed- rano JL, Walma E, Fitzgerald T, Cooney Council on Epidemiology and Preven- wards CA, Goulet O, Hernell O, Koletz- MT, Dudina A, Vahanian A, Camm J, tion; American Heart Association ko B, Lafeber HN, Micheli JL, Mi- De Caterina R, Dean V, Dickstein K, Council on Nutrition, Physical Activity chaelsen KF, Rigo J, Szajewska H, Funck-Brentano C, Filippatos G, Helle- and Metabolism; American Heart As- Weaver LT: Nondigestible carbohy- mans I, Kristensen SD, McGregor K, sociation Council on High Blood Pres- drates in the diets of infants and young Sechtem U, Silber S, Tendera M, sure Research; American Heart Asso- children: a commentary by the Widimsky P, Zamorano JL, Altiner A, ciation Council on Cardiovascular ESPGHAN Committee on Nutrition. J

Bonora E, Durrington PN, Fagard R, Nursing; American Heart Association Pediatr Gastroenterol Nutr 2003; 36: Giampaoli S, Hemingway H, Hakans- Council on the Kidney in Heart Dis- 329–337. son J, Kjeldsen SE, Larsen L, Mancia G, ease; Interdisciplinary Working Group 6 Koletzko B, Kupke I, Wendel U: Treat- Manolis AJ, Orth-Gomer K, Pedersen T, on Quality of Care and Outcomes Re- ment of hypercholesterolemia in chil- Rayner M, Ryden L, Sammut M, search: Cardiovascular risk reduction dren and adolescents. Acta Paediatr

Schneiderman N, Stalenhoef AF, in high-risk pediatric patients: a scien- 1992; 81: 682–685. Tokgözoglu L, Wiklund O, Zampelas A; tific statement from the American 7 Moruisi KG, Oosthuizen W, Opperman European Society of Cardiology (ESC); Heart Association Expert Panel on AM: Phytosterols/stanols lower choles- European Association for Cardiovascu- Population and Prevention Science; the terol concentrations in familial hyper- lar Prevention and Rehabilitation Councils on Cardiovascular Disease in cholesterolemic subjects: a systematic (EACPR); Council on Cardiovascular the Young, Epidemiology and Preven- review with meta-analysis. J Am Coll

Nursing; European Association for tion, Nutrition, Physical Activity and Nutr 2006; 25: 41–48. Study of Diabetes (EASD); Internation- Metabolism, High Blood Pressure Re- 8 McCrindle BW, Urbina EM, Dennison al Diabetes Federation Europe (IDF- search, Cardiovascular Nursing, and BA, Jacobson MS, Steinberger J, Europe); European Stroke Initiative the Kidney in Heart Disease; and the Rocchini AP, Hayman LL, Daniels SR; (EUSI); Society of Behavioural Medi- Interdisciplinary Working Group on American Heart Association Athero- cine (ISBM); European Society of Hy- Quality of Care and Outcomes Re- sclerosis, Hypertension, and Obesity in pertension (ESH); WONCA Europe search: endorsed by the American Youth Committee; American Heart (European Society of General Practice/ Academy of Pediatrics. Circulation Association Council of Cardiovascular

Family Medicine); European Heart 2006; 114: 2710–2738. Disease in the Young; American Heart Network (EHN); European Atheroscle- 3 Aggett PJ, Haschke F, Heine W, Hernell Association Council on Cardiovascular rosis Society (EAS): European guide- O, Koletzko B, Lafeber H, Ormission A, Nursing: Drug therapy of high-risk lip- lines on cardiovascular disease preven- Rey J, Tormo R: Committee report: id abnormalities in children and ado- tion in clinical practice: full text. childhood diet and prevention of coro- lescents: a scientific statement from the Fourth Joint Task Force of the Europe- nary heart disease. ESPGAN Commit- American Heart Association Athero- an Society of Cardiology and other so- tee on Nutrition. European Society of sclerosis, Hypertension, and Obesity in cieties on cardiovascular disease pre- Pediatric Gastroenterology and Nutri- Youth Committee, Council of Cardio-

vention in clinical practice (constituted tion. J Pediatr Gastroenterol Nutr 1994; vascular Disease in the Young, with the

by representatives of nine societies and 19: 261–269. Council on Cardiovascular Nursing.

by invited experts). Eur J Cardiovasc Circulation 2007; 115: 1948–1967.

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218 Pediatric Nutrition in Practice Koletzko B. (ed): Pediatric Nutrition in Practice. Basel, Karger, 2008, pp 219–223

3 Nutritional Challenges in Special Conditions and Diseases

3.17 Enteral Nutrition in Inflammatory Bowel Disease Anne M. Griffiths ؒ Megan Carricato

Key Words testinal inflammation [1] . Since then enteral nu- Enteral nutrition ؒ Crohn disease ؒ Therapy ؒ trition has been an alternative to corticosteroid Growth treatment of active Crohn disease, which is employed more often in children than adults and is more widely accepted in Europe than in North Key Messages America [2] . Efficacy is supported by data from R Enteral nutrition is an alternative to corticosteroid randomized controlled trials versus corticoste- treatment of active inflammation in Crohn dis- roids, and from comparative trials of different ease R When used to induce remission of active Crohn dis- formulae [3, 4]. The mechanism of action remains ease, formulated food should be provided as the conjectural, but may involve alteration in the en- sole source nutrition teric microflora, known to be important in Crohn R 3 Either elemental or polymeric liquid diets may be disease pathogenesis [5]. used Treatment algorithms for Crohn disease are R Supplementary nighttime enteral nutrition (in addition to an ad libitum daytime diet) will facilitate changing rapidly. Increased and earlier use of im- weight gain and linear growth, and may help main- munomodulatory drugs and the availability of tain clinical remission biologic agents have reduced dependence on cor- Copyright © 2008 S. Karger AG, Basel ticosteroids and have made mucosal healing a realistic goal. Nevertheless, for patients willing to accept dietary restrictions and to comply with Introduction the demands of its therapeutic regimens, exclusive enteral nutrition remains a safe alternative Enteral feeding of formulated food can be used to option. The focus of this chapter will be on the correct or prevent malnutrition in inflammatory use of enteral nutrition as primary therapy of in- bowel disease. Its additional benefit as primary testinal inflammation. It aims to instruct physi- therapy was fortuitously discovered when Crohn cians in the selection of patients most likely to disease patients given exclusive enteral nutrition respond, and to provide a very practical guide to pre-operatively experienced improvement not implementation. only in their nutritional status as intended, but also in clinical and laboratory parameters of in- Treatment of Active Crohn Disease Table 1. Protocol for the gradual increase in feeds

Initial hourly infusion rate Most data concerning the efficacy of enteral nu- 20–40 ml/h orally trition in treating active Crohn disease relate to 1–2 ml/kg per hour (using actual body weight) clinical endpoints (i.e. improvement in symp- Increasing enteral feeds toms and laboratory markers of inflammation). Increase by 10 ml every 6–8 h (as tolerated) Clinical response to enteral nutrition has been until 24-hour infusion goal rate is reached associated with endoscopic healing in uncon- (should take 36–48 h to reach goal) trolled studies [6] . Cycling enteral feeds Reduce the number of hours of enteral feeding by Patient Selection 2–3 h each night as tolerated. Divide the total 24-hour goal volume by the desired number of hours Roughly 50–60% of Crohn disease patients treat- for the enteral feed to determine the nasogastric ed with enteral nutrition in clinical trials achieve feed rate clinical remission [3]. As with all therapies, re- Final goal of overnight feeds sponse rates vary depending on the characteris- Feeds should run for 10–14 h overnight tics of the patient population. Patients with mac- (dependent on lifestyle and tolerance) roscopic inflammation located predominantly Maximum feed rate is approximately 6–8 ml/kg in the small intestine are most likely to be suc- per hour cessfully treated with enteral nutrition. Patients with Crohn disease confined to the colon are generally considered to respond less reliably [7] . Recent onset disease may be more responsive than disease of longer duration [3] . Enteral nutri- children learn to insert the tube themselves at tion has not been used to treat active ulcerative night and to administer the required volume of colitis. formula overnight. The tube is removed each morning to facilitate normal daytime activities. Therapeutic Regimens When use over a period of months is contemplat- Exclusive versus Supplementary Enteral ed, an indwelling gastrostomy tube may be in- Nutrition serted. To be successful, enteral nutrition should be administered as the sole source nutrition. Allow- Target Volume and Calories ance of regular food during treatment of active Enteral nutrition should be prescribed in the disease appears to compromise efficacy [8] , and amount necessary to provide 100% of the pa- may also render the child satiated, and less able to tient’s estimated caloric and protein require- tolerate the desired amounts of formulated food. ments. Patients with Crohn disease fail to down- Oral intake of water and/or clear (see-through) regulate their resting energy expenditure in the fluids are allowed. presence of malnutrition, likely due to effects of proinflammatory cytokines [9] . Energy require- Mode of Administration ments may be calculated using normal predictive Liquid diets may be sipped orally (see discussion equations with the patient’s ideal bodyweight for of palatability below), or administered via a silas- height, or using the current weight with allow- tic nasogastric feeding tube (size 6 or 8 French). ance for catch-up weight gain (approximately When a nasogastric feeding tube is used, most 20% extra calories) [10] .

220 Pediatric Nutrition in Practice Infusion rates should be increased in a step- Reintroduction of Solid Food wise manner considering individual tolerance. Although some clinicians have investigated the A sample protocol for the gradual increase to full merits of a specific exclusion diet following in- feeds is given in table 1. Most young patients aim duction of clinical remission by exclusive enteral ultimately to complete the necessary infusion nutrition, most pediatric gastroenterologists over a 10- to 14-hour period each night. simply reintroduce foods gradually. Particularly if the patient is known to have a relatively ste- C h o i c e o f F o r m u l a nosed segment of intestine, it may be prudent to Polymeric, peptide-based and amino acid-based offer a low fiber diet initially, following comple- formulae have all been used to treat active Crohn tion of the enteral nutrition regimen. A sample disease [3] . There is general agreement that the regimen for food reintroduction is given in the protein content of liquid diets does not influence table 2. efficacy [3] . Dietary lipids, however, can modulate inflammation by a variety of mechanisms which influence the cellular production of cyto- Maintenance of Clinical Remission kines and eicosanoids [11, 12] . Excess n-6 polyunsaturated fatty acids (PUFAs) would be ex- One of the limitations of liquid diet therapy has pected to attenuate the effect of enteral nutrition been the observed tendency for symptoms to re- in treating Crohn disease, whereas a relative in- cur promptly following its cessation. In most crease in n-3 PUFAs might be beneficial. studies 60–70% of patients experience a relapse Given the influence of fat content on efficacy, within 12 months of stopping enteral nutrition. a conventional elemental liquid diet (because of Two nutritional strategies can be considered the low fat content) is recommended to optimize to maintain remission: firstly, ‘cyclical exclusive the likelihood of response, if nasogastric tube enteral nutrition’, meaning nocturnal infusion feeding is to be employed. The treatment benefit of a liquid diet and avoidance of regular food in of a low-fat, even n-3 PUFA-enriched elemental 1 of 4 months [14] , or secondly, ‘supplementary 3 diet, compared to a conventional polymeric diet enteral nutrition’, i.e. continuation of nocturnal ! is admittedly small ( 30% difference in response nasogastric feeding 4–5 times weekly as supple- rates) [13] . Therefore, if a child or adolescent is ment to an unrestricted ad libitum daytime diet determined to drink (rather than enterally ad- [15] . minister) formula, a polymeric liquid diet would be more appropriate because of its greater palatability. Facilitation of Linear Growth Duration of Exclusive Enteral Nutrition Impairment of linear growth commonly com- The required duration of exclusive enteral nutri- plicates pediatric Crohn disease. The major tion has not been well defined. Improvements in contributing (and inter-related) factors are the clinical and laboratory parameters occur quickly, direct growth-inhibiting effects of proinflam- often by 2 weeks. Most gastroenterologists, how- matory cytokines produced by the inflamed in- ever, suggest continuing therapy for a minimum testine and chronic undernutrition [16] . Inap- of 4 weeks, longer if the child has not yet reached propriate use of chronic corticosteroid therapy his/her ideal weight. will also impede linear growth. Treatments which are steroid-sparing and which induce and

Enteral Nutrition in Inflammatory Bowel Disease 221 Table 2. Sample regimen for reintroduction of solid foods

Day of Description Examples of foods introduction of foods

1–4 Low fiber White flour breads/bagels/buns/plain pasta/roti/flatbread/rice grains Plain crackers, pretzels, plain cookies (e.g. arrowroot, digestive) Hot cereals: cream of wheat Cold cereals (dry): low fiber, low fat (e.g. no granola) Plain muffins without nuts or dried fruit 5–9 Low fat/fiber Plain and tender cuts of chicken/turkey/lamb/veal/beef/pork meat and Low fat fish alternative Smooth low fat peanut butter (limited amounts) sources Tofu Eggs (prepared with little to no fat) Note: avoid fried, cured, and processed meats; regular fat peanut butter, dried or canned peas, beans, lentils 10–14 Low fiber Raw fruits without membrane and skin vegetables All canned/stewed fruits without skin and seeds and fruit Tender, cooked vegetables, no skins/seeds Note: vegetables and fruit should be prepared using low fat cooking methods Soups with allowed meat, vegetables, rice, noodles (avoid highly seasoned soups, cream soups) 15–17 Low fat Low fat milks, yogurts, cheeses dairy products 18 Regular diet Increase fat and fiber gradually to assess tolerance as tolerated

sustain mucosal healing will be associated with Conclusions reduced cytokine production and linear growth facilitation. Resumption of normal linear • Exacerbations of Crohn disease, particularly growth during enteral nutrition maintenance involving the small intestine, may be treated regimens is a marker of therapeutic success. with 4–6 weeks of exclusive enteral nutrition Conversely, if a child merely gains weight but • Because relapse is common following cessa- does not grow in height, it can be assumed that tion of enteral nutrition, strategies to main- the inflamed intestine is not healing, and that tain remission must be planned other methods of treating the inflammation • Nutritional strategies include cyclical exclu- must be adopted. sive enteral nutrition (1 of 4 months) or nocturnal supplementary enteral nutrition (in addition to regular ad libitum daytime intake) • Normal (and catch-up) linear growth are markers for the success of therapy

222 Pediatric Nutrition in Practice References

1 Voinkt AJ, Echave V, Feller JH, et al: 6 Fell JM, Paintin M, Arnaud-Battandier 11 Gorard DA: Enteral nutrition in Experience with elemental diet in the F, et al: Mucosal healing and a fall in Crohn’s disease: fat in the formula. Eur

treatment of inflammatory bowel dis- mucosal pro-inflammatory cytokine J Gastroenterol Hepatol 2003: 15: 115– ease. Is this primary therapy? Arch mRNA induced by a specific oral poly- 118.

Surg 1973; 107: 329–333. meric diet in paediatric Crohn’s dis- 12 Gassull MA, Fernandez-Banares F,

2 Levine A, Milo T, Buller H, Markowitz ease. Aliment Pharmacol Ther 2000; 14: Cabre E, et al: Fat composition may be J: Consensus and controversy in the 281–289. a clue to explain the primary therapeu- management of pediatric Crohn dis- 7 Afzal NA, Davies S, Paintin M, et al: tic effect of enteral nutrition in Crohn’s ease: an international survey. J Pediatr Colonic Crohn’s disease in children disease: results of a double blind ran-

Gastroenterol Nutr 2003; 36: 464–469. does not respond well to treatment domized multicentre European trial.

3 Griffiths AM, Ohlsson A, Sherman PM, with enteral nutrition if the ileum is Gut 2002; 51: 164–168.

Sutherland LR: Meta-analysis of enteral not involved. Dig Dis Sci 2005; 50: 1471– 13 Zachos M, Tondeur M, Griffiths AM: nutrition as a primary treatment of 1475. Enteral nutritional therapy for induc- active Crohn’s disease. Gastroenterol- 8 Johnson T, Macdonald S, Hill SM, et al: ing remission in Crohn’s disease.

ogy 1995; 108: 1056–1067. Treatment of active Crohn’s disease in Cochrane Database Syst Rev 2007; 1: 4 Heuschkel RB, Menache CC, Megerian children using partial enteral nutrition CD000542. JT, Baird AE: Enteral nutrition and cor- with liquid formula: a randomized con- 14 Belli DC, Seidman E, Bouthillier F, et

ticosteroids in the treatment of acute trolled trial. Gut 2006; 55: 356–361. al: Chronic intermittent elemental diet Crohn’s disease in children. J Pediatr 9 Azcue M, Rashid M, Griffiths A, improves growth failure in children

Gastroenterol Nutr 2000; 31: 8–15. Pencharz PB: Energy expenditure and with Crohn’s disease. Gastroenterology

5 Lionetti P, Callegari ML, Ferrari S, et body composition in children with 1988; 94: 603–610. al: Enteral nutrition and microflora in Crohn’s disease: effect of enteral nutri- 15 Wilschanski M, Sherman P, Pencharz pediatric Crohn’s disease. J Parent En- tion and treatment with prednisolone. P, et al: Supplementary enteral nutri-

teral Nutr 2005; 29:S173–S178. Gut 1997; 41: 203–208. tion maintains remission in paediatric

10 Gavin J, Anderson CE, Bremner AR, Crohn’s disease. Gut 1996; 38: 543–548. Beattie RM: Energy intakes of children 16 Ballinger A: Fundamental mechanisms with Crohn’s disease treated with en- of growth failure in inflammatory teral nutrition as primary therapy. J bowel disease. Horm Res 2002;

Hum Nutr Diet 2005; 18: 337–342. (suppl 1):7–10.

Enteral Nutrition in Inflammatory Bowel Disease 223 Koletzko B. (ed): Pediatric Nutrition in Practice. Basel, Karger, 2008, pp 224–228

3 Nutritional Challenges in Special Conditions and Diseases

3.18 Nutrition in Cystic Fibrosis Michael Wilschanski

Key Words spiratory, gastrointestinal, hepatobiliary, repro- -Cystic fibrosis ؒ Nutritional status ؒ Pancreatic ductive and sweat glands. The lack of CFTR func -enzymes ؒ Gastrostomy tion in the pancreatic duct is responsible for ob struction and autodigestion of the pancreas in utero leading to exocrine pancreatic insufficien- Key Messages cy (PI) in 85% of CF infants. R Survival from cystic fibrosis (CF) has substantially The early growth of infants with CF PI is de- improved over the past 4 decades. The advance in pendent on the age at diagnosis. Clinical diagno- nutritional management is one factor which has sis may be difficult unless meconium ileus oc- contributed to this change curs, typically in only 15% of the cases. The re- R This chapter will review the basic defect of CF and how it influences nutritional status maining patients are diagnosed later, mainly R Normal growth and development can be achieved presenting as failure to thrive with steatorrhea in CF, and to this end nutritional counseling is para- accompanied in some cases with respiratory mount at all ages symptoms. An increasing number of countries R The prevention and early detection of growth fail- have initiated newborn screening for CF using a ure is the key to successful nutritional counseling R An approach to the CF patient who is not thriving serum marker of PI, which has been shown to fa- and an outline for nutritional management are pro- cilitate an earlier diagnosis with better growth posed Copyright © 2008 S. Karger AG, Basel and nutritional status [2] . Longer-term studies after neonatal screening are now revealing reduced pulmonary disease progression [3] . Numerous studies have shown that underweight and poor linear growth in children and Introduction malnutrition in adults are independent factors predicting mortality [4, 5]. Together with this, Cystic fibrosis (CF) is the most common life- undernutrition has been shown to have an ad- threatening autosomal recessive disease in Cau- verse effect on the outcome of lung transplanta- casians with an incidence of 1 in 2,500 live births. tion [6]. These data reinforce the importance of The disease is caused by mutations in the cftr prevention and early detection of growth failure gene on chromosome 7 which codes for a cAMP- leading to the aggressive management of nutri- regulated chloride channel [1]. Non-functioning tional deficits at all ages. This has led to the pub- CFTR protein affects epithelial ion and water lication of nutritional guidelines in Europe and transport in a variety of organs including the re- in North America [7, 8] . I n f a n t s Table 1. Recommended dietary macronutrient composition (% of energy intake) in CF and non-CF patients

The evaluation of an infant with CF should be ex- Non-CF CF pedited. If PI is established by tests for steatorrhea and indirect pancreatic function tests, pancreatic Protein 10–15 15 enzyme replacement therapy should be initiated Carbohydrate 55–60 35–40 as soon as possible. Breastfeeding is encouraged. Fat 30 45–50 Enzymes are given with all foods and milk products including predigested formulas containing medium-chain triglyceride. Babies require powder which should be taken with fruit sauce and a School-Age Children pretreatment application of a thin layer of zinc- based baby ointment to the mouth and perianal This is the age at which to encourage the child to area to avoid skin excoriation. The enzymes obtain a basic knowledge of the physiological should be administered at the beginning of and processes eventually leading to increasingly tak- during the meal. The initial dose of enzymes ing responsibility for practical enzyme and nutri- should be approximately 5,000 IU lipase/kg per tional management. day. The dose may be increased gradually according to symptoms and objective assessment of growth and fat absorption. In many instances, ca- Adolescence loric density needs to be increased and this may be achieved by fortifying breast milk, adding fat This stage is associated with increased growth, or carbohydrate or concentrating the formula. puberty and increased physical activity. This Once solid food is introduced, enzymes should be adds up to markedly increased nutritional re- titrated by fat intake. The maximum dose is quirements which are often difficult to attain. 10,000 IU lipase/kg per day. Fat-soluble vitamin Pulmonary infections are more common, as is (ADEK) supplementation should be initiated ac- the onset of CF-related diabetes and, in a small 3 cording to the current recommendations [7, 8]. minority of cases, CF-related liver disease. Fe- Hyponatremic alkalosis may occur in infants es- male patients are at a greater risk for nutritional pecially during the summer months; supplemen- failure at this time [9]. This may be partly due to tation with sodium chloride is recommended. dissatisfaction with weight and body shape in healthy adolescent females. Growth retardation and pubertal delay occur with increased social Toddlers pressure and psychosocial stress. These factors must be considered when nutritional advice is As infants are introduced to table foods, it is im- provided to teenagers. portant that the diet should be balanced, with moderately increased fat and protein content ( table 1). Parents need to be in control, routinely add- Follow-Up ing calories to maintain growth. The child with CF should avoid low-fat food and grazing. The dieti- A formal dietary assessment should be undertak- cian should promote positive interactions around en annually. This should incorporate a review of meals. Mealtime must not turn into a battleground nutritional intake, enzyme dose and timing of which is the catalyst for poor feeding behavior. administration, and vitamin supplements. An-

Nutrition in Cystic Fibrosis 225 Cellular Pancreatic Iatrogenic defect? Intestinal Psychogenic Biliary Gastrointestinal

Needs + Losses + Intake

Anorexia Vomiting

Energy deficit

Weight loss Pulmonary infections

Respiratory Lung Immune

muscles parenchyma dysfunction

Deteriorating lung function Fig. 1. The pathogenesis of energy imbalance in cystic fibrosis.

thropometry should be performed regularly and ration in lung function. Malnutrition is known to body mass index percentile charts are now con- cause immune dysfunction. Taken together, a vi- sidered the most accurate interpretation of nutri- cious cycle is established leading to further dete- tional status. Bone health is an increasing con- rioration. cern in CF [10] . Bone mineral density and body composition should be assessed by dual-energy X-ray absorptiometry [11] . Management of the Malnourished Child

Once poor growth is identified, patients must be When Things Go Wrong evaluated more frequently. The visits must include medical, nutritional and behavioral input. Figure 1 demonstrates the pathogenesis of mal- Figure 2 shows an algorithm for the workup. nutrition in CF [12]. As pulmonary disease wors- ens and resting energy expenditure increases, other factors predispose to an energy deficit. The Nutritional Intervention frequency and severity of infections increase, inducing anorexia and/or vomiting and reduce in- If the reason for the poor weight gain is poor intake. Weight loss results causing loss of muscle take, the first strategy must be to gradually in- tissue, respiratory muscle wasting reduces effec- crease ca lor ies at mea lt i mes. T h is may be ach ieved tive coughing further contributing to the deterio- in mild cases by a step-wise approach. Firstly, to-

226 Pediatric Nutrition in Practice creases of energy intake in some studies [13]. The Poor weight gain long-term effect of supplements is controversial and they must not take the place of meals [14]. If this fails, enteral feeding should be commenced Assess pulmonary status/disease activity [15] . The choice of access should be made together with the family but generally nasogastric feeding is started before gastrostomy placement. Ca- Nutritional assessment lorically dense formulas (1.5–2.0 kcal/ml) are well tolerated and initially nocturnal infusion is Feeding behavior evaluation encouraged to promote normal eating behavior during the day. However, in some cases, 24-hour

Maximize dietary intake nasogastric feeding may be required. Our experi-

ence is that once families see success after 6–8 weeks of nasogastric feeding, gastrostomy placement is welcomed. Patients with excessive nau- Psychosocial consultation (adherence) sea, bloating or vomiting may benefit from pro-

72-Hour fecal fat balance kinetic drugs or semi-elemental or elemental formula.

Other etiologies Assess enzyme dose GERD CFRD Conclusions Constipation DIOS Consider acid suppression

Bacterial overgrowth • The overall goal is that every patient with cys- IBD Etc. Enteral feeding tic fibrosis should achieve normal growth • This requires regular surveillance including age-specific individualized expert advice with Fig. 2. Plan of action for poor weight gain in cystic fibro- nutritional care plans to suit each patient 3 sis. GERD = Gastroesophageal reflux disease; CFRD = • Nutritional intervention should be appropri- cystic fibrosis-related diabetes; DIOS = distal intestinal ately timed to influence the evolution of the obstruction syndrome; IBD = inflammatory bowel disease. disease • Nutritional support is an integral part of the care of patients with cystic fibrosis • At diagnosis all patients require pancreatic gether with the parents an ‘individualized plan of and nutritional assessment action’ surrounding the preferred foods of the • Patients must be carefully monitored and di- child may be used. For example, if the child likes etary counseling provided fish, the parents should be encouraged to prepare • Nutritional evaluation and support are age-re- this in a high-calorie setting by frying the fish lated and adding mayonnaise. The parents should be • Patients who fail to respond require enteral encouraged to give ice-cream, cakes and other supplementation high-calorie foods with liberal administration of • Nutritional status impacts on the progression extra oil and glucose polymers. The next stage is of cystic fibrosis the administration of high-energy supplements which have been shown to achieve significant in-

Nutrition in Cystic Fibrosis 227 References

1 Welsh MJ, Tsui L, Boat TF, et al: Cystic 6 Snell GI, Bennetts K, Bartolo J, et al: 11 Kerem E, Conway S, Elborn S, Heijer- fibrosis; in Scriver C, Beaudet AL, Valle Body mass index as a predictor of sur- man H; Consensus Committee: Stan- D (eds): The Metabolic and Molecular vival in adults with cystic fibrosis re- dards of care for patients with cystic Basis of Inherited Disease ed 7. New ferred for lung transplantation. J Heart fibrosis: a European consensus. J Cystic

York, McGraw-Hill, 1995, pp 3799– Lung Transplant 1998; 17: 1097–1103. Fibros 2005; 4: 7–26. 3876. 7 Sinaasappel M, Stern M, Littlewood J, 12 Durie PR, Pencharz PB: A rational ap- 2 Farrell PM, Kosorok MR, Laxova A, et et al: Nutrition in patients with cystic proach to the nutritional care of pa- al: Nutritional benefits of neonatal fibrosis: a European consensus. J Cystic tients with cystic fibrosis. J R Soc Med

screening for cystic fibrosis. Wisconsin Fibros 2002; 2: 51–75. 1989; 82(suppl 16):11–20. Cystic Fibrosis Neonatal Screening 8 Borowitz D, Baker RD, Stallings V: 13 Steinkamp G, Demmelmair H, Ruhl-

Study Group. N Engl J Med 1997; 337: Consensus report on nutrition for pedi- Bagheri I, et al: Energy supplements 963–969. atric patients with cystic fibrosis. J Pe- rich in linoleic acid improve body

3 Sims E, Clark A, McCormick J, et al: diatr Gastroenterol Nutr 2002; 35: 246– weight and essential fatty acid status of Cystic fibrosis diagnosed after 2 259. cystic fibrosis patients. J Pediatr Gas-

months of age leads to worse outcomes 9 Lai HC, Kosorok MR, Sondel SA, et al: troenterol Nutr 2000; 31: 418–423. and requires more therapy. Pediatrics Growth status in children with cystic 14 Kalnins D, Corey M, Ellis L, et al: Fail-

2007; 119: 19–28. fibrosis based on the National Cystic ure of conventional strategies to im- 4 Kraemer R, Rudelberg A, Hadorn B, Fibrosis Patient Registry data: evalua- prove nutritional status in malnour- Rossi E: Relative underweight in cystic tion of various criteria used to identify ished adolescents and adults with

fibrosis and its prognostic value. Acta malnutrition. J Pediatr 1988; 132: 478– cystic fibrosis. J Pediatr 2005; 147: 399–

Paediatr Scand 1978; 67: 33–37. 485. 401. 5 Sharma R, Florea VG, Bolger AP, et al: 10 Buntain HM, Schluter PJ, Bell SC, et al: 15 Jelalian E, Stark LJ, Reynolds L, Seifer Wasting as an independent predictor of Controlled longitudinal study of bone R: Nutritional intervention for weight mortality in patients with cystic fibro- mass accrual in children and adoles- gain in cystic fibrosis: a meta analysis. J

sis. Thorax 2001; 56: 746–750. cents with cystic fibrosis. Thorax 2006; Pediatr 1988; 132: 486–492.

61: 146–154.

228 Pediatric Nutrition in Practice Koletzko B. (ed): Pediatric Nutrition in Practice. Basel, Karger, 2008, pp 229–233

3 Nutritional Challenges in Special Conditions and Diseases

3.19 Heart Disease Michelle Steltzer

Key Words dominant cause of growth failure or failure to -Congenital heart disease ؒ Failure to thrive ؒ thrive in infants with CHD, particularly with he Growth disturbance modynamically significant CHD [1] . Clinically significant CHD and the impact on growth are often most challenging for the practi- Key Messages tioner. These infants and children typically are R Inadequate caloric intake and increased metabolic those with cyanotic CHD, large left to right shunt, demand are felt to be predominant causes of valve regurgitation, congestive heart failure growth failure in patients with congential heart (CHF), depressed function, or pulmonary hyper- disease (CHD) tension [1] . Any hemodynamic impairment in R Approaches to optimize the inadequate nutritional needs include: higher volumes, fortified breast the presence of CHF can negatively impact the milk or higher caloric formulas, and supplemental infant or child with CHD [1, 3]. Clinically, CHF tube feeding is often seen with poor feeding, tachypnea, hepa- R If present, gastroesophageal reflux should be tomegaly and tachycardia [4] (table 1). treated, particularly with clinically significant CHD Surgical or interventional procedures can in- R Additional risk factors that may negatively impact clude one or multiple procedures over infancy growth include: genetic abnormalities, prematurity, extracardiac anomalies, and recurrent respira- and childhood, placing increased nutritional tory infections needs on the infant or child. Failure to provide 3 R A multidisciplinary approach is important to opti- these nutritional needs can further impact post- mize growth and minimize growth disturbances in operative morbitidy and length of stay [5] in ad- patients with CHD dition to long-term growth and development. Copyright © 2008 S. Karger AG, Basel A common risk factor for impaired growth in patients with CHD is gastroesophageal reflux (GER), particularly with clinically significant Introduction CHD [7] . In addition, the presence of other risk factors for growth impairment include prematu- Adequate enteral nutrition is essential for infants rity, genetic and extracardiac anomalies, and and children with heart disease to sustain appro- recurrent respiratory infections [6, 7] . When priate growth in weight and height over time. contributing risk factors are present, it is essential Acyanotic lesions typically impact weight more that these risk factors be addressed with the than height, whereas cyanotic lesions impact primary care physician and other specialists col- weight and height [1, 2]. Growth parameters for laboratively, thus promoting a multidisciplinary infants and children with congenital heart dis- approach to meet the growth and nutritional ease (CHD) are not well established in the litera- needs of infants and children with CHD (see fig. ture. Inadequate caloric intake is felt to be a pre- 1a and b). Table 1. Cardiac lesions at risk for growth delay [1, 2, 6] ications are common in the management of CHF and poor ventricular function [1] . Digoxin, diuret- Acyanotic CHD lesions: weight growth disturbancea – Aortic stenosis ics (furosemide, aldactone, aldactazide and diuril), – Pulmonary stenosis and afterload-reducing agents (captopril, enala- – Coarctation of the aorta pril, and lisinopril) are common medication choic- – Ventricular septal defectb es available for use as clinically indicated in con- b – Patent ductus arteriosus sultation with pediatric cardiology. Electrolytes – Atrial septal defectb – Atrial ventricular valve regurgitationb may need to be monitored if increasing the renal – Semilunar valve regurgitation – less commonb solute load with higher concentrations of formula [8] , adjusting or maintaining on diuretics, dehy- Cyanotic CHD lesions: weight and height growth dration, viral illness, or intolerance of feeds is a disturbancec – Double outlet right ventricle concern. Oxygen therapy may be utilized in those – Transposition of the great arteries patients with pulmonary hypertension and hypox- – Tetralogy of Fallot with or without pulmonary atresia emia [1] . Availability of an infant scale sensitive to – Tricuspid atresia 10 g or greater is useful in tracking appropriate – Hypoplastic left heart syndrome weight gain in infants with CHD. The literature a If significant shunting and/or presence of pulmonary shows that infants, especially with single ventricle hypertension is noted, then height disturbances may physiology, tend to show a plateau of growth at be observed. about 4 months of age [9] . Earlier intervention ul- b Lesions prone to pulmonary over-circulation have a timately provides the patient with less preoperative greater impact on growth. c Hypoxemia accompanied by CHF has a greater im- nutritional depletion and a more hemodynamical- pact on growth. Hypoxemia length in years is thought ly stable heart disease lesion at an earlier age. to impact growth retardation. Optimize Caloric Intake If gastrointestinal function is adequate, enteral feeds should always be utilized, preferentially Monitoring Growth and CHD over parenteral nutrition. Enteral feeds are more physiologic, safer, more accessible, and cost-ef- Surgical or Interventional Procedure fective than parenteral nutrition. Rapid advance- The timing and sequence of surgical and/or inter- ment to full enteral feeds as clinically tolerated is ventional catheterization procedures depend on becoming more of a current trend in care [3, 5]. the individual patient’s anatomy, hemodynamic Increasing caloric density of feedings is a prac- data, and clinical status upon consultation with tical strategy to meet nutritional needs in patients the pediatric cardiologist and cardiothoracic sur- with CHD. Term neonatal goal feedings should geon. The inability to maintain a steady incline in target 150 ml/kg per day and 120 kcal/kg per day the plotted growth or a plateau in growth may be for patients with significant CHD, such as shunt- an indication that an intervention might be re- dependent single ventricle anatomy. Given the quired to promote growth and development. higher caloric needs of these patients with hemodynamically significant CHD, breast milk is often Medical Management not optimal for growth when utilized solely. Medical management of growth disturbances fo- The caloric density of breast milk can be in- cuses on symptomatic improvement of CHF symp- creased by adding powdered formula to reach toms and promotion of optimal growth. Under the about 80–90 kcal/100 ml. Non-breastfeeding in- direction of a pediatric cardiologist, multiple med- fants may receive commercially available stan-

230 Pediatric Nutrition in Practice Nutrition and congenital heart disease

Surgical Optimize nutritional and intake to meet caloric medical management demands

Address structural Consults: Medical strategies Promote high calorie lesions causing Nutrition to relieve CHF enteral feedings growth failure when Speech therapy symptoms and ﬂuids medically indicated Gastroenterology

Medications and For insuﬃcient PO: oxygen as directed Consider NG, GT, or GJ by cardiologist for nutritional support a Monitor growth

Monitoring growth and CHD

Non-cardiac Surgical or dard formulas (60–70 kcal/100 ml). Standard etiology interventional caloric preparation of breastmilk or formula procedure can be increased by adding more powder to water ratio or, additionally, with fortification options (MCT oil or protein supplements) to Modes of Medical enteral management achieve ;80–90 kcal/100 ml with reasonable feeding 3 patient tolerance. Feedings of ;100 kcal/100 ml are also an option but carry a higher risk of in- Appropriate Optimize consults: caloric intake tolerance in infancy. Increasing caloric density Speech, nutrition, can decrease the feeding volumes if GER and b gastroenterology volume sensitivity are an issue. Many recipe choices are available in practice, please check Fig. 1. Nutrition and CHD: practical approach to achiev- with your nutritionist or health care specialist ing growth. CHF = Congestive heart failure; PO = oral; for details on the most practical approach for NG = nasogastric; GT = gastrostomy tube; GJ = gastroje- your patient and family. junal. Monitoring growth and tolerance of feedings is an important assessment required at the initiation of feeds, advancement of feedings, and over Bottlefed infants gained a median of 20 g/day, time [10] . Infants and children have been report- combination breastfed and bottlefed infants ed to need up to 150 kcal/kg per day or more, par- gained a median of 5 g/day, and exclusively ticularly with significant CHF, stress, and sur- breastfed infants lost a median of 49 g/day [12] . gery [6, 11] . Boctor et al. [12] identified growth Older infants and children can increase their following cardiac surgery for infants with CHD. calories by drinking whole milk and high calorie

Heart Disease 231 enteral supplement feedings (see Chapter 3.3). dent physiology and CHF is currently optimizing Avoidance of non-caloric drinks should be feedings prior to discharge. The feeding plan con- stressed. Small meal portions and fluid volume sists of breast milk and formula fortified to 27 cal/ can help improve caloric intake. Foods high in oz or 90 kcal/100 ml, and the goal volume is 480 protein, carbohydrate, and fats should be encour- ml/day or 60 ml feeds PO/NG 8 times per day. aged [10] . This provides 137 ml/kg per day and 123 kcal/kg per day. The infant clinically is doing well (satura- Appropriate Consults tions on room air of 85%, heart rate regular and Consultations with a nutritionist, speech thera- sinus at 130 beats per minute, comfortable respi- pist, and gastroenterologist can be used when ratory effort maintained on aspirin, digoxin, concerns arise regarding optimizing caloric in- lasix, and ranitidine), tolerates full goal feedings, take, ability to feed orally, strategies to improve demonstrates weight gain of 10 g per day consis- oral feeding and decrease fatigue, and tolerance tently for 2–3 days, and is now able to consistent- of feedings and/or GER. ly take orally 40 ml or more per feeding. It is reasonable to remove the NG stimulus in Modes of Enteral Nutrition the nare and to trial an all-PO plan for 24 h. Ad Ideal enteral nutrition is all oral (PO). A notable libitum or on demand oral feedings should be en- number of patients are unable to meet their nutri- couraged for 20–30 min maximum time to feed tional needs. If oral feeding is insufficient, meth- every 2.5 to 3.5 h. A primary feeder (parents, ods to deliver optimal nutrition in neonates and speech therapist, nursing, etc.) should be available infants can be achieved by supplemental tube feed- and encouraged to participate in feedings during ings. Steltzer et al. [10] in 2006 describe a feeding this trial to encourage the best possible outcome. strategy for neonates postoperatively following If the infant is unable to meet maintenance cardiac surgical palliation or complete repair. fluid requirements within 24 h, reassessment of Rapid advancement of full enteral feeds in ne- clinical status by health care providers is neces- onates and infants is best achieved initially with a sary for potential alteration in plan of care. This more flexible long-dwelling 6.5–8 French naso- plan may include many options: continuation of gastric (NG) feeding tube. These tubes can last for all-PO trial with close monitoring, adjustment of up to 30 days and are more secure than oral gas- diuretics, replacement of NG resuming prior tric tubes. Advancement in the volume and ca- feeding plan, and discussing potential need for loric density of feedings can be done with PO/NG other means to provide nutrition. feeding plans to promote optimal oral feeding The use of an NG tube at home tends to be a skills. PO feeds no longer than 20–30 min are at- center-specific preference due to the risk of car- tempted first, followed by the remaining volume diovascular compromise with placement, dis- of the feed given via the NG tube by gravity and a lodgement, and vasovagal response [10] . Surgical pump, with a total PO and NG feeding time of 60 or percutaneous endoscopic gastrostomy tubes min to allow adequate gastric emptying before are a secure option to provide oral and gastros- the next feed is started. tomy tube feedings. In addition, they can also be Once goal calories are reached for 2 or more utilized for continuous jejunal feeds if gastric days and the infant is taking greater than 50% of feeds are not tolerated. Studies show that continu- volume needed to meet goal calories, the NG tube ous 24-hour feedings require less energy expendi- can be removed for a 24-hour trial of all-PO feed- ture and are a safe, effective way to increase nutri- ings. For example, a 3.5 kg infant status post stage ent intake and improve overall nutritional status 1 Norwood surgical palliation with shunt depen- [13, 14] . Practically, for delivery at home, gastric

232 Pediatric Nutrition in Practice bolus feedings during the day for 4–5 feeds, and a Conclusions continuous gastric drip feed at night can be used [10] . Jejunal feeds must be given via continuous • A multifaceted approach by healthcare pro- drip and typically over many hours up to 24 h a viders is essential to optimize growth and day. Schedules can be adjusted to allow for some minimize growth disturbances in patients pump time off, should PO be ordered in the feed- with congenital heart disease (CHD) ing plan in consultation with specialists. • Meeting increased caloric needs is essential to the promotion of growth in infants and chil- Non-Cardiac Etiology dren with CHD and requires diligent care by The presence of other risk factors including ge- practitioners netic abnormalities, prematurity, extracardiac • Gastroesophageal reflux is common in in- anomalies, GER, and recurrent respiratory infec- fants, particularly with clinically significant tions (causing hypoxemia) can also impact CHD, and should be treated growth [1, 7]. Management of GER with an acid- • Prevention of infectious and viral illness is neutralizing agent such as ranitidine, lansopra- important to prevent dehydration, hypoxia, zole, or omeprazole can be used to prevent ero- and further hemodynamic compromise sive esophagitis. To prevent recurrent respiratory • Appropriate and early consults with pediatric infections, palivizumab can be used in high-risk cardiology, cardiothoracic surgery, nutrition, patients with CHD to prevent respiratory syncy- speech, and gastroenterology should be uti- tial viral infections. Pneumococcal vaccine with lized to promote the growth and development continuous antibiotic prophylaxis can be used in of patients with CHD patients with asplenia according to the routine immunization guidelines of the American Acad- emy of Pediatrics [1] . 3 References

1 Rosenthal A: Nutritional consider- duration of hospital stay: a randomized 10 Steltzer M, Rudd N, Pick B: Nutrition

ations in the prognosis and treatment trial. J Pediatr 2004; 145: 761–766. care for newborns with congenital

of children with congenital heart dis- 6 Norris MK, Hill CS: Nutritional issues heart disease. Clin Perinatol 2006; 32: ease; in Suskind RM, Lewinter-Suskind in infants and children with congenital 1017–1030. L (eds): Textbook of Pediatric Nutri- heart disease. Crit Care Nurs Clin 11 Barton JS, Hindmarsh PC, Scrimgeour

tion, ed 2. New York, Raven Press, North Am 1994: 6:153–163. CM, et al: Energy expenditure in con- 1993, pp 383–391. 7 Smith P: Primary care in children with genital heart disease. Arch Dis Child

2 Linde LM, Dunn OJ, Schireson R, et al: congenital heart disease. J Pediatr Nurs 1994; 70: 5–9.

Growth in children with congenital 2001; 16: 308–319. 12 Boctor DL, Pillo-Blocka F, McCrindle

heart disease. J Pediatr 1967; 70: 413–419. 8 Cunningham KF, McLaughlin M: Nu- BW: Nutrition after cardiac surgery for 3 Dooley KJ, Bishop L: Medical manage- trition; in Kessler DB, Dawson P (eds): infants with congenital heart disease.

ment of the cardiac infant and child Failure to Thrive and Pediatric Under- Nutr Clin Pract 1999; 14: 111–115. after surgical discharge. Crit Care Nurs nutrition: A Transdisciplinary Ap- 13 Schwarz SM, Gewitz MH, See CC, et al:

Q 2002; 25: 98–104. proach. Baltimore, Brookes, 1999, pp Enteral nutrition in infants with con- 4 Park M: Congestive heart failure; in 99–120. genital heart disease and growth fail-

Craven L (ed): Pediatric Cardiology for 9 Jaquiss RD, Ghanayem NS, Hoffman ure. Pediatrics 1990; 86: 368–373. Practitioners, ed 3. St. Louis, Mosby- GM, et al: Early cavopulmonary anas- 14 Schuurmans FM, Pulles-Heintzberger Year Book, 1996, pp 401–411. tomosis in very young infants after the CF, Gerver WJ, et al: Long-term growth 5 Pillo-Blocka F, Adatia I, Sharieff W, et Norwood procedure: Impact on oxy- of children with congenital heart dis- al: Rapid advancement to more concen- genation, resource utilization, and ease: a retrospective study. Acta Paedi-

trated formula in infants after surgery mortality. J Thorac Cardiovasc Surg atr 1998; 87: 1 2 5 0 – 1 2 5 5 .

for congenital heart disease reduces 2004; 127: 982–989.

Heart Disease 233 Koletzko B. (ed): Pediatric Nutrition in Practice. Basel, Karger, 2008, pp 234–238

3 Nutritional Challenges in Special Conditions and Diseases

3.20 Renal Disease Lesley Rees ؒ Jean-Pierre Guignard

Key Words Chronic Kidney Disease and Dialysis Renal failure, acute, chronic ؒ Dialysis Adequate nutritional intake can be difficult to achieve in children with chronic renal failure (CKD). This is reflected in poor growth, a pro- Key Messages gressive problem as renal function deteriorates, R Dietary intervention is crucial to the successful so that around 50% of children are below the nor- management of acute renal failure, and can pre- mal range for height at the start of renal replace- vent or delay the need for dialysis ment therapy. Short stature is associated with in- R Careful nutritional support early in the course of creased morbidity and mortality. chronic kidney disease (CKD) can improve growth, The purpose of dietary intervention in the morbidity and mortality in children of all ages Copyright © 2008 S. Karger AG, Basel care of patients with CKD is to: • Control the symptoms of uremia: inadequate energy from non-protein sources will result in the use of dietary protein for energy, and inad- Introduction equate protein will result in catabolism of body tissues, both by increasing plasma urea Acute Renal Failure (and potassium) levels Acute renal failure (ARF) is a sudden, potentially • Prevent complications: particularly renal bone reversible, inability of the kidneys to maintain disease due to inappropriate intakes of phos- normal body composition, usually accompanied phate and calcium by oliguria (urine output ! 0.5 ml/kg per hour or • Promote optimum growth: by the provision of !1 ml/kg per hour in a neonate). This results in adequate energy, protein, vitamins and min- salt and water retention, catabolism and meta- erals bolic disturbances (low bicarbonate and calcium, • Preserve residual renal function: by the provi- high potassium, phosphate and urea). sion of adequate, but not excessive, protein Dietary intervention is an important part of the management of ARF because it can: • Prevent catabolism (which contributes to hy- Acute Renal Failure perkalemia and hyperphosphatemia) • Control the volume of fluid intake Most children are unable to meet nutritional • Control metabolic abnormalities (urea, calci- goals orally (e.g. due to nausea or neurological um, phosphate, potassium) impairment). Furthermore, maintenance of ade- • Aid recovery quate nutrition may be compromised by fluid re- Table 1. Specifications for the diet in acute renal failure Energy (ARF) Spontaneous oral intake may be inadequate. In Volume Depends on daily fluid removal the first instance, oral energy supplements may (urine 8 dialysate losses) be enough, but if the growth rate begins to decel- erate, enteral feeding by nasogastric tube or gas- Energy High, to prevent catabolism trostomy should be introduced ( fig. 2 ). The aim is Salt Low, except in the unusual circumstance to achieve the estimated average requirement, us- of polyuric ARF ing height age for infants and children ! 0.4th Protein Low, to prevent a high plasma urea, unless centile for height. This allows catch-up growth in on prolonged peritoneal dialysis when a children under 2 years and gives some benefit in higher protein intake may be required older children. Energy intake may need to be in- Phosphate Low, to prevent hyperphosphatemia creased to replace feed lost by vomiting. Vomit- ing may respond to oral prokinetic agents but, if severe, Nissen fundoplication may need to be considered. Children on peritoneal dialysis (PD) striction so that feeds need to be concentrated absorb glucose from the dialysate (8–12 kcal/kg and are often unpalatable. Many children, there- body weight per day), which should be taken into fore, need enteral feeding. Parenteral nutrition account in children who gain weight excessive- should only be considered if enteral nutrition is ly [3]. not tolerated. The feed in a child with conservatively man- Protein aged ARF is particularly important because it The aim for protein in CKD is the reference nu- can control metabolic and fluid abnormalities so trient intake (RNI; again using height age for in- that the need for dialysis can be prevented in the fants and children ! 0.4th centile for height), short term. However, if oliguria is prolonged it is which most children achieve spontaneously. rarely possible to provide adequate nutrition so However, when the glomerular filtration rate 2 3 that dialysis becomes necessary to ‘provide space’ falls below 25 ml/min per 1.73 m , reduction of for feeds, allowing the diet and fluid allowance to protein intake may be necessary. The aim is to be liberalized. keep plasma urea levels ! 20 mmol/l in infants Dietary specifications for ARF are shown in and children under 10 years, and ! 30 mmol/l in table 1, and the plan for management in figure 1 older children with a normal plasma albumin [1]. and normal growth. The first step is to ensure adequate energy intake. If urea levels remain raised despite this, protein intake should then be Chronic Kidney Disease and Dialysis reduced in 0.2-g/kg steps towards the RNI. Wean- ing solids should be low in protein and phos- Anorexia and vomiting (due to abnormal gastric phate, e.g. baby rice, pureed fruits and vegetables. motility and delayed emptying) are common in As the infant takes more protein from solids, pro- CKD; therefore, prevention of malnutrition or its tein intake from milk should be adjusted. Cow’s treatment is a crucial part of management. Loss milk and cow’s milk products may need to be re- of height potential is greatest in infancy (the time stricted. About 70% of protein should be from when there is the greatest possibility for catch-up high biological value sources, e.g. meat, fish, growth with nutritional intervention), but can cheese, eggs or milk (NB: phosphate content may occur at any age [2]. limit the use of cheese, eggs and milk). The re-

Renal Disease 235 Day 1 High-energy protein-free carbohydrate-containing ﬂuids e.g. solution of dextrin maltose (glucose polymer)

Concentration depends on degree of nausea, vomiting, diarrhea: • Infants 15% dextrin maltose • 1–2 years 20% dextrin maltose • >2 years 25% dextrin maltose

Day 2 Consider introduction of protein depending on degree of uremia

Urea 30–40 mmol/l Urea 40 mmol/l Start 0.5 g protein/kg dry weight per day Protein-free high-energy ﬂuids for further 24 h Infants – diluted baby milk + dextrin maltose Children – diluted whole protein feed + dextrin maltose

Day 3 Increase/introduce protein depending on degree of uremia Maximize energy intake using carbohydrate and fat supplements as tolerated

Urea 20–30 mmol/kg Urea 30–40 mmol/kg Increase protein to 1 g/kg dry weight per day As for day 2

Day 4 onwards Normalize eating and drinking patterns as renal function improves

Urea 20–30 mmol/kg Urea <20 mmol/kg As for day 3 At least the RNI protein for height age in infants or chronological age in children

Fig. 1. Nutritional management of acute renal failure. RNI = Reference nutrient intake.

maining protein is given as lower biological value Potassium sources, e.g. bread, rice, potatoes, pasta and bis- Plasma potassium levels 1 6.0 mmol/l are most cuits, allowed freely and only restricted if uremia often due to inadequate energy; energy intake is uncontrolled despite optimum energy intake. should therefore be optimized. If hyperkalemia is In contrast, children on dialysis need increased 1 6.5 mmol/l or persistent, a low potassium, low protein to compensate for dialysate losses, which phosphate formula can be mixed with the feed. are greatest with PD, particularly so in infants and after peritonitis (table 2). Energy-dense feeds Phosphate and Calcium providing as much as 2 cal/ml can be used in chil- Control of plasma phosphate and calcium is nec- dren on a fluid restriction [4]. essary to prevent renal bone disease. Dietary phosphate may need restriction when the glo-

236 Pediatric Nutrition in Practice CKD/dialysis

Assessment of dietary intake, height, weight, head circumference and pubertal stage at each visit

Inadequate intake but Declining rate of growth growth rate still normal or food/supplement refusal

Breastfed infants may need additional nasogastric supplements Older children: High energy foods and Nasogastric or gastrostomy drinks supplemented with Whey-based enteral feed for <2 years carbohydrate of age, whole protein enteral feed for or >2 years of age, supplemented with fat Pediatric sip feed or carbohydrate or both

Fig. 2. Management of feeds in chronic kidney disease (CKD).

merular filtration rate falls below the normal Table 2. Protein requirements in children on dialysis [6] range, and almost always when !50 ml/min per 2 Boys and girls Recommended protein intake 1.73 m ( table 3 ). Calcium absorption can be low g/kg per day due to inadequate hydroxylation of vitamin D by peritoneal dialysis hemodialysis the kidneys, and can be increased by administration of vitamin D in its active form. Preterm 3.0–4.0 3.0 3 0–6 months 2.1–3.0 2.1 Vitamins and Minerals 6–12 months 2.0–3.0 1.5–2.0 The RNIs for all micronutrients also apply for 1–2 years 2.0–3.0 1.5–1.8 2–puberty 2.5 1.0–1.5 children with CKD, except for vitamins A and D. Pubertal 2.0 1.0–1.5 Renal excretion of vitamin A metabolites is im- Postpubertal 1.5 1.0–1.5 paired in CKD and high plasma levels can be associated with hypercalcemia, anemia and hyperlipidemia. Vitamin D is usually prescribed in its activated form at a dose that requires regular adjustment to prevent renal osteodystrophy. If the Table 3. Phosphate restriction in chronic kidney disease (CKD) diet is inadequate or severely restricted, a vitamin and mineral supplement may be needed. Chil- Bodyweight, kg Phosphate restriction, mg/day dren on PD require vitamin C, pyridoxine and folic acid to offset dialysate losses. Hyperhomo- <10 <400 cysteinemia occurs in CKD and is an indepen- 10–20 <600 20–40 <800 dent risk factor for cardiovascular disease. Folic >40 <1,000 acid lowers plasma homocysteine levels, so folic acid supplementation is likely to be beneficial [5].

Renal Disease 237 Conclusions Chronic kidney disease and dialysis: • Individual dietary prescription is essential Acute renal failure: • Enteral feeding is indicated in both infants • Dietary intervention is necessary from the on- and children when oral intake is inadequate to set maintain growth • Strict control of fluid, energy, protein, potas- • The dietary prescription will vary depending sium and phosphate intake can delay the need on the severity of chronic kidney disease and for dialysis but make it difficult to achieve ad- type of dialysis equate nutrition • Protein requirements are higher on peritoneal • Diet can be liberalized by dialysis dialysis, particularly after peritonitis • If peritoneal dialysis becomes prolonged, pro- • Vitamin preparations containing vitamin A tein intake may need to be increased should not be used

References

1 Rees L, Webb N, Brogan P (eds): Acute 3 Clinical practice guidelines for nutri- 5 Shaw V, Coleman J: Nutritional man- Renal Failure in Paediatric Nephrology. tion in CRF. K/DOQI, National Kidney agement of renal disease in childhood.

Oxford University Press, 2007, pp 360– Foundation. Am J Kidney Dis 2000; Ann Nestlé 2003; 61: 21–31. 384. 35(suppl 2):S1–S140. 6 Rees L: Management issues in children 2 Rees L, Shaw V: Nutrition in children 4 Paediatric supplement; in Treatment of with renal disease; growth, nutrition with CRF and on dialysis. Pediatr Adults and Children with Renal Fail- and pubertal development; in Hodson

Nephrol 2007; 22: 1689–1702. ure. London, Royal College of Physi- E, Eddy A (eds): BMJ evidence based cians, 2002. publications, 2008, in press.

238 Pediatric Nutrition in Practice Koletzko B. (ed): Pediatric Nutrition in Practice. Basel, Karger, 2008, pp 239–243

3 Nutritional Challenges in Special Conditions and Diseases

3.21 Anorexia Nervosa and Bulimia Nervosa Ascensión Marcos

Introduction Key Words ؒ Eating disorders ؒ Adolescents ؒ Malnutrition Behavioral therapy Anorexia nervosa (AN) and bulimia nervosa (BN) are eating disorders (EDs) which usually start in the mid-teens and affect around 10% of teenagers. However, a very early start during pu- Key Messages berty is becoming more frequent, and occasion- R It is important that the patient is informed about ally some cases start later, in their 30s or 40s. In the possibility of suffering from an eating disorder both syndromes the patients aim to loose weight which needs to be evaluated by a physician. If it is confirmed, the physician must ask the patient who and be thin, despite their extreme emaciation, is going to inform his/her parents (the patient or due to a distorted body image and weight (fea- the physician) tures are shown in tables 1 and 2 ). R When the patient’s life is in danger, due to a very Common features found in these patients are fast weight loss or suicide attempt (the most com- also dissatisfaction and impassive attitudes to- mon cause of death), then it is mandatory that the patient be admitted to hospital. Nowadays all gether with their admiration of misunderstood hospitals are ready to treat any medical imbalance fashion trends. This lifestyle philosophy could complication or suicide risks simply be unconsious alarm signs ( table 3 ) ex- 3 R The treatment of patients with eating disorder pressed by patients towards their families and must be in specialized centers and units, no matter friends, although this theory is still controversial whether they suffer from acute clinical symptoms and under discussion. Table 4 shows other com- or a relapse. Afterwards, patients must continue treatment either as outpatients or at a mental mon characteristics upon physical examination. healthcare center. However, in partially stable cas- Patients with EDs are malnourished, although es, maintenance of treatment can be followed with their symptoms are somewhat different from nutritional support and nonspecific psychotherapy those shown in typical protein-energy malnutri- R Blood analysis features: hypercholesterolemia, tion ( table 5 ). Thus, this particular situation of hypercortisolemia, hypertestosteronemia, borderline hemoglobin ( ^ 12 g/ml), leucopenia, relative malnutrition has been defined as relative pro- lymphocytosis, depleted T and NK cells and in- tein-energy malnutrition [1] . creased or maintained B cells Moreover, alterations in the immune systems R Other symptoms, such as dehydration, convulsions of these patients are seen, although surprisingly (low potassium and phosphorus blood levels), and they have repeatedly been found to be free from intoxication, should bring the patient to the emer- immunologically related diseases, such as com- gency services, and once these medical complications are solved, patients can be treated in the out- mon viral infections or allergies [2–8] . In fact, patient department data in the scientific literature are very contro- Copyright © 2008 S. Karger AG, Basel versial due to the heterogeneity of ED patients Table 1. The pathophysiological features of restrictive Table 2. The pathophysiological features of the purging anorexia nervosa and the binge/purging subtype of an- type and the non-purging type of bulimia nervosa cur- orexia nervosa currently used in the diagnosis rently used in the diagnosis

Restrictive anorexia nervosa Purging type of bulimia nervosa 1 A disturbed perception of body weight and self- 1 Binge eating, defined as the rapid, compulsive image consumption of a large quantity of food in a very 2 Self-starvation with significant weight loss in short short period of time, usually less than 2 h periods of time 2 Self-induced vomiting 3 Primary or secondary amenorrhea 3 Abuse of laxatives, diuretics and anorexigens 4 Physical hyperactivity and sleep disturbances 5 Bizarre behavior and attitudes about food Non-purging type of bulimia nervosa 1 Alternative periods of restricting diets and binge- Binge/purging subtype eating 1 All the characteristics cited above 2 Compulsive physical exercise 2 Self-induced vomiting 3 Compensatory means (self-induced vomiting, 3 Abuse of laxatives, diuretics and anorexigens abuse of laxatives, diuretics and anorexigens)

Table 3. The most frequent alarm signs expressed by Table 4. Physical examination characteristics eating disorder patients 1 Fragile nails and hair 1 Moodiness 2 Dehydrated and pale skin 2 An intense desire to be alone, especially at meal 3 Orange-colored palms of hands times 4 Amenorrhea in women 3 A compulsive desire to do exercise at any time of 5 Bradycardia and low pulse the day 6 When vomiting is present: wounds in the corner 4 A significant weight loss or fluctuating weight of the mouth and Russell signs (wounds in knuckles changes and palms of hands) 5 Multiple and unjustified visits to the toilet 6 Unjustified missing of meals at home

Table 5. Nutrient intake pattern of anorexia nervosa pa- Table 6. Heterogeneity of patients with eating disor- tients ders

1 Primary nutrient inadequacy, avoiding 1 Each patient can show variable degrees of carbohydrate and fat intake malnutrition 2 Protein intake: apparently quite preserved 2 Adaptive mechanisms triggered by the restricted 3 Micronutrient deficiencies are not as frequent as intakes expected (due to the quality of the food choices of 3 Neuroendocrine and psychopathological the patients), at least until the illness is far advanced alterations together with energy restrictions affect the immune system in a complex way

These premises could explain the controversial findings in patients with eating disorders regarding immune function and their apparent resistance to infection.

240 Pediatric Nutrition in Practice (table 6) and the different factors involved, such Differential Diagnoses to Be Considered as age at the start of illness, evolution time, early diagnosis, and appropriate treatment. A typical pattern has been defined in EDs, which is characterized by the following two main features: (1) obsession to be slim, in the case of AN Recognition of Different Types of Eating this feeling is accompanied by significant weight Disorders loss and amenorrhea, and (2) severe body dissatisfaction. Apart from typical EDs, such as AN and BN, oth- Patients with BN are also characterized by er types must be taken into account: binge-eating disturbed eating attitudes showing a lack of eat- disorders which represent stable syndromes, and ing control, very frequently developing binge- EDs not otherwise specified (EDNOS). eating followed by purging behavior (vomiting EDNOS have been defined to be a separate and laxative abuse), which may be interchange- cluster of EDs among borderline women, rather able. However, the use of multiple purging meth- than a prodromal or residual form of a more ods has been associated with greater severity over clear-cut case of AN or BN. EDNOS represent the time [10] . most common EDs diagnosed in specialized In addition, patients with obsessive-compul- treatment settings. sive disorder have been shown to score signifi- Partial EDNOS syndromes have also been re- cantly higher than healthy control subjects on all ported in the literature, and are most frequent eight subscales of the Eating Disorder Inventory: both in adolescents and adults. drive for thinness; bulimia; body dissatisfaction; EDNOS-purging only has been found to be ineffectiveness; perfectionism; interpersonal dis- clinically significant, lying somewhere between trust; interceptive awareness, and maturity fears. women with lifetime BN purging subtype and healthy controls [9] . Other atypical ED syndromes to bear in mind How to Manage Malnutrition in Eating are: psychogenic vomiting, functional dysphagia, Disorders 3 craving, and alexithymic AN. Alexithymia core features are: difficulties in Food and nutritional recovery are key aspects in identifying and describing feelings; difficulties the treatment of ED. Therapists must be con- in distinguishing feelings from the bodily sensa- scious of the great importance of the fact that pa- tions of emotional arousal; impaired symboliza- tients have to be fed despite their difficulties in tion as evidenced by a paucity of fantasies and eating properly. other imaginative activity, and a tendency to fo- Patients with AN reluctantly accept external cus on external events rather than inner experi- control from their therapists. ence. As patients with EDs suffer from mental dis- The possible link between alexithymia and turbances, it is necessary to implement a life plan psychosomatic or psychopathological disorders jointly developed by nutritionists, psychiatrists is now well documented. Overweight and obesity and/or psychologists. To this end, there must be are very frequent in those patients suffering from specialized treatment units, in which nurses are binge-eating. In particular, alexithymia has been especially well trained. suggested to be frequently observed in obese or In order to be re-fed, a significant number of bulimic patients. patients must be admitted to hospital for 30–40 days.

Anorexia Nervosa and Bulimia Nervosa 241 If a good nursing team is available, tube feed- ity-based and during the first steps are more fo- ing use is exceptional and is only used when a cused on negative reinforcements than on posi- natural re-feeding method does not work. Enter- tive reinforcements and awards. al feeding is not necessary, unless a false reduc- Both during admission to the hospital or in tion of admission is found by the therapist. Par- daycare centers, behavioral therapies are realized enteral nutrition is rarely necessary. by nurses, at home by parents or relatives, and in If re-feeding is carried out at home, patients all cases, they must be supervised by a specialized and their parents must be trained. psychiatrist or psychologist. The use of dining rooms in daycare centers is very helpful, and patients can follow an eating plan under the intensive care of nurses. C o n c l u s i o n s Food supplements can be used, especially during admission, in order to reinforce re-feeding • Patients must be treated by multidisciplinary and especially micronutrient and fiber intake. groups including psychiatrists, psychologists, However, it is very important that patients be- nutritionists, dietitians, endocrinologists, and come used to eating common foods at appropri- pediatricians ate times during the day. • Diagnosis and treatment must be adequate at very early stages of the illness to enhance the prognosis Principles of Behavioral Therapy • Patients must be treated by professionals when the first symptoms are seen Behavioral therapy is the first part of the psycho- • Although in most cases clinical analyses seem therapy that will last for 4–5 years. This therapy to be correct, it is important to highlight that includes several psychological techniques applied these patients show a trend towards leucope- to patients in order to regain common and nor- nia, together with relative lymphocytosis and mal food habits which have been lost or perturbed depleted cell-mediated immune function due to the mental disorder. • Nevertheless, patients with eating disorders These techniques involve strong pressure on surprisingly show a low risk of suffering from the patients to help them eat properly, including infections and allergies, although when recov- body position, how to use cutlery, feeding rhythm, ering from anorexia nervosa or bulimia ner- resting time after eating, and avoiding compen- vosa the opposite is the case satory maneuvers. These techniques are author-

References

1 Marcos A: Eating disorders: a situation 3 Marcos A, Varela P, Toro O, et al: Inter- 4 Nova E, Marcos A: Immunocompe- of malnutrition with peculiar changes actions between nutrition and immu- tence to assess nutritional status in in the immune system. Eur J Clin Nutr nity in anorexia nervosa. A one year eating disorders. Exp Rev Clin Immu-

2000; 54(suppl 1):S61–S64. follow-up. Am J Clin Nutr 1997; 66 nol 2006; 2: 433–444. 2 Marcos A, Varela P, Santacruz I, et al: (suppl 3):S485–S490. 5 Nova E, Gómez-Martínez S, Morandé Nutritional status and immunocompe- G, Marcos A: Cytokine production by tence in eating disorders. A compara- blood mononuclear cells from in-

tive study. Eur J Clin Nutr 1993; 47: 787– patients with anorexia nervosa. Br J

793. Nutr 2002; 88: 183–188.

242 Pediatric Nutrition in Practice 6 Marcos A, Nova E, López-Varela S: Be- 8 Corcos M, Guilbaud O, Paterniti S, et 10 Haedt AA, Edler C, Heatherton TF, havior of the immune system in eating al: Involvement of cytokines in eating Keel PK: Importance of multiple purg- disorders; in Fuller R, Perdigon G (eds): disorders: a critical review of the hu- ing methods in the classification of Gut Flora, Nutrition, Immunology and man literature. Psychoneuroendocri- eating disorder subtypes. Int J Eat Dis-

Health. Oxford, Blackwell, 2003, nology 2003; 28: 229–249. ord 2006; 39: 648–654. pp 137–154. 9 Wade TD: A retrospective comparison 7 Birmingham CL, Hodgson DM, Fung J, of purging type disorders: eating disor- et al: Reduced febrile response to bacte- der not otherwise specified and buli-

rial infection in anorexia nervosa pa- mia nervosa. Int J Eat Disord 2007;

tients. Int J Eat Disord 2003; 34: 269– 40: 1–6. 272.

Anorexia Nervosa and Bulimia Nervosa 243 Koletzko B. (ed): Pediatric Nutrition in Practice. Basel, Karger, 2008, pp 244–247

3 Nutritional Challenges in Special Conditions and Diseases

3.22 Hemato-Oncology John W.L. Puntis

Introduction Key Words Malignant disease ؒ Bone marrow/stem cell transplantation ؒ Mucositis ؒ Enteral tube feeding ؒ Leukemia accounts for 30–45% of childhood Parenteral nutrition cancers, lymphomas for 9–15%, and solid tumors (e.g. medulloblastoma, Wilm’s, neuroblastoma, etc.) for around 40%. Malnutrition is common in Key Messages children with malignant disease, with prevalence R Malnutrition is a common complication of malig- estimates ranging from 6 to 50% depending on nant disease and its treatment, and it is most likely the type, stage and location of the tumor. The to occur in advanced stage solid tumors, acute highest risk posed to nutritional status comes myeloblastic leukemia, and bone marrow/stem cell transplantation from advanced stage solid tumors, acute myelo- R Nutritional support is a major part of therapy; there blastic leukemia, multiple relapse leukemia, head is no evidence that extra nutrients promote tumor and neck cancer, medulloblastoma, and bone growth marrow or stem cell transplantation. Cachexia R The aims of nutritional support are to reverse mal- (weakness, anorexia, weight loss, altered sub- nutrition if present at diagnosis, to prevent deterio- strate metabolism) is common and related to ration in nutritional status during treatment, and to promote normal growth metabolic demands related to both tumor burden R Children at low nutritional risk require high energy and the effects of treatment. Cytokines such as supplements that can be taken by mouth; they tumor necrosis factor, interleukin-1 and -6 and benefit from flexibility in mealtimes and menus interferon- ␥ also play an important role. Rather R When oral energy intake is inadequate, enteral than conserving energy and protein reserves in tube feeding should be used; this is usually well tolerated and improves wellbeing even in children response to starvation, the child with malignant undergoing intensive chemotherapy disease may increase energy expenditure, prote- R Parenteral nutrition is reserved for those children olysis and gluconeogenesis, more characteristic with severe gastrointestinal symptoms related to of acute metabolic stress. underlying disease, chemotherapy or radiother- General risk factors for malnutrition are shown apy Copyright © 2008 S. Karger AG, Basel in table 1 . Learned food aversion associated with nausea-inducing treatment sometimes leads to anticipatory vomiting. Chemotherapy may adversely affect food intake and gastrointestinal function by causing oral or esophageal ulceration, altered taste perception, anorexia, nausea, vomit- Table 1. Risk factors for nutritional compromise ing, and enteritis with malabsorption and diar- Decreased food intake rhea. Radiation therapy to the head and neck can Inadequate amount of food offered cause mucositis, anorexia, nausea, vomiting, dys- Unappetizing food; lack of flexibility in meeting phagia, dry mouth and altered taste, while radia- child’s preferences tion to the abdomen may cause enteritis, some- Too much food times followed by stricturing of the bowel. ‘Forced’ feeding Reduced appetite from illness Bone marrow transplantation (BMT) or stem Symptoms associated with disease or treatments, cell transplantation are used in children with a e.g. nausea, vomiting, sore mouth, pain, diarrhea, range of malignant and non-malignant condi- breathlessness, etc. tions. Chemotherapy and/or radiation therapy Repeated fasting for treatments or procedures Mucositis, swallowing or chewing difficulties are used to reduce host cells to the point that do- Difficulty self-feeding nor stem cells will engraft (allogeneic BMT), or to Poor child/carer interaction at mealtimes reduce the tumor burden and rescue the patient Impaired conscious level with his/her own stem cells (autologous BMT). Increased nutritional requirements Priming chemotherapy causes severe nausea, Illness/metabolic stress vomiting and oral ulceration, and is often associ- Wound or fistula losses ated with diarrhea, protein losing enteropathy, Impaired ability to absorb or utilize nutrients and depletion of zinc and electrolytes [1, 2]. Most Due to disease or treatment, e.g. chemotherapy children undergoing BMT stop eating either as a causing enteropathy or pancreatic exocrine impairment result of these side effects, or because eating be- Infection as a consequence of immunosuppression comes an issue over which they can exercise control where otherwise they have little or none. Im- pairment of gastrointestinal barrier function increases the risk of viral, bacterial and fungal infection. Episodes of sepsis are associated with tritional support promotes tumor growth. Base- 3 protein catabolism and negative nitrogen bal- line nutritional status should be established, in- ance. Enteral feeds should be prepared in a man- cluding eating habits and any problems over food ner that renders them low in bacterial load (‘clean perceived by the family. Weight measurement is feeds’); parenteral nutrition (PN) may be neces- inaccurate as an indicator of nutritional status in sary, but when tolerated enteral tube feeds (ETFs) children with a large tumor mass, and mid upper are associated with better nutritional response arm circumference and skinfold thickness mea- and sense of wellbeing. surements are more reliable methods of assessment and monitoring [3] . Neutropenic patients must avoid food that may carry a high microbial Provision of Nutritional Support load, such as poorly cooked meats, soft cheeses, pate and shellfish; however, most infections are The multidisciplinary hematology-oncology team hospital-acquired and not food-borne, so over-re- should develop a nutritional care plan for each pa- striction of food choices may be counterproduc- tient. The goals of nutritional support are to re- tive. Mucositis (painful mouth ulcers 8 superin- duce morbidity and minimize or prevent compli- fection), vomiting and anorexia often limit oral cations such as infection and growth failure; im- intake. Routine saline mouth washes are used, to- proved nutritional intake can help promote a gether with adequate pain relief (opiates if neces- sense of wellbeing. There is no evidence that nu- sary). Frequent small meals of appetizing food are

Hemato-Oncology 245 Table 2. Enteral tube feeding: problems and potential solutions

Symptom Cause Possible solution

Diarrhea Unsuitable feed in a child with Change to hydrolyzed formula or modular feed impaired gut function Excessive infusion rate Slow rate and increase as tolerated Intolerance of bolus feeds Frequent, smaller feeds, or change to continuous feeds High feed osmolarity Build up strength of feed slowly and give by continuous infusion Microbial contamination Use sterile, commercially produced feeds when possible; of feed prepare other feeds in clean environment Drugs (e.g. antibiotics, laxatives) Review drug prescription Nausea/ Excessive infusion rate Slowly build up feed infusion vomiting Slow gastric emptying Encourage lying on right side; prokinetics Constipation Maintain regular bowel habit with adequate fluid intake, fiber-containing feed and/or laxatives Medicines given at the same Allow time between giving medicines and giving feed, or time as feed stop continuous feed for a short time Psychological factors Review feeding behavior; consider referral to psychologist Regurgitation/ Gastroesophageal reflux Correct positioning; feed thickener; drugs; continuous feeds; aspiration jejunal tube (consider fundoplication) Dislodged tube Secure tube adequately and regularly review position Excessive infusion rate Slow infusion rate Intolerance of bolus feeds Smaller, more frequent feeds, or continuous infusion

more likely to be accepted, and advice with regard Enteral Tube Feeding and Parenteral to the use of high calorie foods should be given Nutrition routinely. There should be flexibility with regard to menu choice, mealtimes and parental involve- ETF or PN are likely to be needed when ment; children on the ward should be encouraged • The child is malnourished at diagnosis to eat together at mealtimes. Tastes may be bitter • Loss 1 5% body weight during treatment or metallic with some drugs (e.g. procarbazine, • Weight for height ! 90% cyclophosphamide) or food may have no taste at • Drop in weight across two centiles all. Some children develop a liking for strong fla- • Food intake ! 80% estimated requirement vors (pickles, spices). Serving food with sauces • Triceps skinfold thickness ! 5th centile and gravies will increase moisture and help swal- • Bone marrow transplant patient lowing if the mouth is dry. Food can be purchased Long-term use of ETF in infants often leads to from the shop/canteen or brought in from home later feeding difficulties and early advice should if tempting meals cannot be provided in hospital. be sought from a speech and language therapist. The use of a reward system (star chart) may moti- Gastrostomy may be considered if tube feeding is vate some younger children to eat, but rewards required for more than 4 weeks, or if the nasogas- need to be appropriate to the child’s age and goals tric tube is not tolerated (e.g. severe mucositis; must be achievable and relevant. vomiting). Ideally, older children should be al-

246 Pediatric Nutrition in Practice lowed to choose between a nasogastric tube or mia, about 40% may later become obese [6] . Cra- percutaneous endoscopic gastrostomy tube. Tube nial irradiation is also a risk factor for developing feeds are generally given overnight to allow nor- obesity. In addition to an increase in fat mass, late mal activities and oral intake during the daytime. nutritional complications from treatment of Tube feeding [4] may result in a number of com- childhood malignancies include a reduction in plications including vomiting, regurgitation/as- growth rate and in lean body mass. Reduced bone piration and diarrhea (see table 2 for potential so- mineral density can result from decreased activ- lutions). Whereas the enteral route should be ity, reduced calcium intake and the effects of cor- used for nutritional support whenever possible, ticosteroid treatment; under-mineralization may PN and ‘bowel rest’ are sometimes necessary persist in a small proportion of patients. when chemotherapy causes severe gastrointestinal side effects. Standard PN regimens may be used, although the possibility of refeeding syn- Conclusions drome should be considered in the malnourished patient [5] , and regimens may require modifica- Always try to tion in the light of nutritional response. It is im- • Identify child’s favorite foods; these are best portant to consider and regularly review the ob- avoided whilst having chemotherapy as they jectives of nutritional support in individual pa- may develop a permanent dislike to them tients. Monitoring will include assessment of • Offer small, frequent meals nutritional intake, anthropometry, biochemical • Encourage dietary supplements and hematological parameters, general clinical • Provide skilled dietetic supervision state, gastrointestinal function, and feeding tube/ • Manage side effects of chemotherapy effec- central venous catheter integrity. tively (nausea, vomiting) • Consider need for tube feeding early, especially in high nutritional risk patients Late Nutritional Complications • Remember that a child may eat better at 3 home A decrease in physical activity during illness • Use parenteral nutrition when appropriate leads to a reduction in energy expenditure. In (i.e. when enteral feeds are precluded by gas- children treated for acute lymphoblastic leuke- trointestinal dysfunction)

References

1 Papdopoulou A, Williams MD, Dar- 3 Smith DE, Stevenson MCG, Booth IW: 5 Afzal NA, Addai S, Fagbemi A, et al: byshire PJ, Booth IW: Nutritional sup- Malnutrition at diagnosis of malignan- Refeeding syndrome with enteral nu- port in children undergoing bone mar- cy in childhood is common but mostly trition in children: a case report, litera-

row transplantation. Clin Nutr 1998; 17: missed. Eur J Pediatr 1991; 150: 315– ture review and clinical guidelines.

57–63. 323. Clin Nutr 2002; 21: 515–520. 2 Papadopoulou A, MacDonald A, Wil- 4 Smith DE, Handy DJ, Holden CE, et al: 6 Oeffinger KC, Mertens AC, Sklar CA, et liams MD, et al: Enteral nutrition after An investigation of supplementary al: Obesity in adult survivors of child- bone marrow transplant. Arch Dis naso-gastric feeding in malnourished hood acute lymphoblasic leukaemia: a

Child 1997; 77: 131–136. children undergoing treatment for ma- report from the Childhood Cancer Sur-

lignancy: results of a pilot study. J Hum vivor Study. J Clin Oncol 2003; 21: 1359–

Nutr Diet 1992; 5: 85–91. 1365.

Hemato-Oncology 247 Koletzko B. (ed): Pediatric Nutrition in Practice. Basel, Karger, 2008, pp 248–253

3 Nutritional Challenges in Special Conditions and Diseases

3.23 Intensive Care Jessie Hulst ؒ Hans Van Goudoever

Key Words creased mortality and morbidity, including a -Intensive care ؒ Burn injury ؒ Trauma ؒ Critical higher risk of infections due to poor immune de illness fense, wound healing problems, reduced gut function, longer dependency on mechanical ventilation and longer hospital stay [2, 5] . Key Messages Studies have shown that the nutritional status R Malnutrition leads to increased morbidity and of children admitted to a PICU deteriorates dur- mortality in pediatric hospital patients, with paring hospitalization [3] , as children often do not ticularly severe consequences in critically ill chil- receive adequate feeding. dren Besides underfeeding, also overfeeding has R Both under- and overfeeding have negative consequences negative consequences. It is of no benefit in main- R Trauma and burn injury require additional atten- taining a lean body mass, which results in the ex- tion with regard to nutritional requirements cessive synthesis of fat. This may induce hepatic R Guidelines in this area are not evidence-based be- steatosis and impaired liver function, and in- cause little research has been conducted crease the risk of hyperglycemia. Hyperglycemia Copyright © 2008 S. Karger AG, Basel itself results in a higher mortality and morbidity in critically ill adults [6] . The synthesis of fat increases CO2 production which may contribute to Introduction ventilatory compromise, with longer ventilator dependency [1] . During critical illness and recovery thereafter, Trauma and burn injury in children are associ- adequate nutritional support is an essential aspect ated with increased systemic energy expenditure of the clinical management of pediatric intensive (EE), severe muscle catabolism and wasting, and care patients [1] . Adequate feeding is essential for growth delay. Appropriate nutritional support as complete recovery and normal functioning of the part of daily therapeutic interventions has been growing child. Thus clinicians in the pediatric in- shown to improve mortality and morbidity [7] . tensive care unit (PICU) are challenged to provide adequate nutrition for optimal tissue synthesis and immune function while avoiding complica- Nutritional Requirements tions of under- or overfeeding. The prevalence of malnutrition is high among A major problem in clinical practice is to define children admitted to a PICU, including burn and the nutritional requirements for critically ill chil- trauma patients [2–4] . Protein-energy malnutri- dren, as demands range widely with altered met- tion in hospital patients is associated with in- abolic states determined by the children’s age and Table 1. Factors influencing energy expenditure in criti- high in this category. The extent of hypermetabo- cally ill children lism is related to the percentage of burned surface Increase in energy expenditure area. In trauma patients, especially with head in- Sepsis jury, energy demands are increased. Surgery Activity E n e r g y Fever In practice, the daily energy demands of critical- Weaning from mechanical ventilation Drugs: pressor agents, catecholamines ly ill children should be individually calculated Pain, anxiety based on one of the following methods: Decrease in energy expenditure (1) Measurement of EE by indirect calorimetry Mechanical ventilation (total daily energy requirement) in sedated, Temperature-controlled environment ventilated children, and resting EE (REE) in Drugs: sedatives, analgesics, ␤-blockers non-ventilated children Progression of sepsis to septic shock (2) Estimation of REE by predictive equations based on weight, age and sex (3) Estimation using dietary reference intakes (DRI) for healthy children matched for age Table 2. Schofield formulas for estimation of resting energy expenditure (kcal/day) [10] and sex The preferred method is measuring the EE, as Age Boys Girls several factors present in the critically ill child years can influence basic metabolic rate (table 1). The 0–3 60.9!weight (kg) – 54 61.0!weight (kg) – 51 measured EE is the minimum amount of energy 3–10 22.7!weight (kg) + 495 22.5!weight (kg) + 499 needed. The Schofield formula is a useful alterna- 10–18 17.5!weight (kg) + 651 12.2!weight (kg) + 746 tive [10] for estimating REE and is shown in table 2. Additional factors should be taken into ac- In order to calculate total energy needs, the following additional factors must be taken into account. count to calculate total energy needs such as ac- Illness factor of critically ill children: 1.2–1.6 in PICU pa- tivity factor, illness factor, growth factor and 3 tients, 1.4 in burn patients, and 1.3–1.5 in trauma pa- absorption coefficient in case of enteral feeding. tients. In general, infants require 10–20% more calories Activity factor of critically ill children: 1.0–1.1. Growth factor of critically ill children: 1.0 in the acute when fed enterally than when fed parenterally, phase; in reconvalescent phase: 1.3 when age <4 months, whereas the differences are smaller in children 1.1 when age 4–12 months, 1.0–1.04 for older children. (close to 10%) primarily because of more effective enteral absorption with older age. In table 3 an overview is given of the nutritional requirements in critically ill children fed nutritional status. Moreover, metabolic respons- enterally. es may greatly vary as well, depending on the nature of the injury and the variability of the indi- Amino Acids vidual response to the same type of injury [8, 9] . Both protein synthesis and protein breakdown The exaggerated catabolic response that is typ- are intensified in critical illness, but the latter ically seen in children hospitalized for burn inju- predominates. Thus, critically ill children typi- ries, coupled with exudation of nutrients through cally manifest a net negative protein balance, the damaged skin, means that requirements for which may clinically be noted by weight loss, neg- energy, protein and other nutrients are especially ative nitrogen balance and skeletal muscle wast-

Intensive Care 249 Table 3. Nutritional requirements in critically ill children Fats fed enterally Lipid metabolism is generally accelerated by ill- Age Energy g/kg per day ness and physiologic stress, and lipids are a prime kcal source of energy. A minimum linoleic acid intake protein fat carbo- of 0.1 g/kg per day should be administered to in- hydrates fants and older children in order to prevent es- 0–1 month 110–120 3–4 3–5 14–17 sential fatty acid deficiency. The dosage of fat 1–12 months 100–110 2.5–3 3–4 14–16 should not exceed the capacity for lipid clearance 1–6 years 90–110 2–3 2–3 14–16 and should be adapted if marked hyperlipidemia 7–12 years 70–90 2–3 2–3 11–13 >12 years 35–70 1–2 2–3 3–9 occurs.

Based on Koletzko et al. [18]. Trauma Trauma and specifically head injury should receive 140% of REE in non-paralyzed patients, and 100% in paralyzed patients. This recommen- Table 4. Formulas for estimating energy needs in pedi- dation is derived from adult guidelines since only atric burn patients [19] limited studies in children are available. Age, years Daily requirement Burn Injury 0–1 2,100 kcal/m2 + 1,000 kcal/m2 burned In pediatric burn patients several additional for- 1–10 1,800 kcal/m2 + 1,300 kcal/m2 burned mulae for determining energy needs are in use 2 2 >10 1,500 kcal/m + 1,500 kcal/m burned ( table 4 ), but have been shown to underestimate m2 = Body surface area. EE [15] . The measurement of EE is highly recommended in this population. Protein requirements in burned children are much higher than in normal children. In addition ing. Fortunately, supplementation of amino acids to increased loss of protein across the burn wound, does improve protein balance by increasing pro- there is a great demand for protein for wound heal- tein synthesis [11, 12] . It is possible to change a ing, host defense and gluconeogenesis as amino catabolic state into anabolism, even at low energy acids become a primary source of energy. Current intakes, when the child is provided with enough recommendations for patients with burns to more amino acids. Providing adequate dietary protein than 10% of the body surface area are 20% total is, therefore, a very important nutritional inter- kcal provided from protein/amino acids, 40–50% vention in critically ill children. from carbohydrates, and up to 30% from fats.

Carbohydrates Glucose is the major energy source in critical ill- Nutritional Support ness, but excessive carbohydrate intake results in a high CO2 production. A high carbohydrate intake Indication and Goal is associated with lipogenesis and less fat oxidation Nutritional support is important in the manage- [13] . Reduced morbidity and mortality have been ment of the critically ill patient when oral food observed with the use of insulin to maintain strict intake is inadequate or not possible. It is employed normoglycemia in critically ill adults [14] . No to minimize the loss of lean body mass and sup- studies in children have been published as yet. port the synthesis of critical visceral proteins.

250 Pediatric Nutrition in Practice Table 5. Main reasons for inadequate delivery of nutrients and recommendations for prevention

Causes of noncompliance Recommendation for prevention

Fluid volume restriction Condensation of formula e.g. cardiac patients Gastrointestinal dysfunction1 Transpyloric enteral feeding Prokinetics (Additional) parenteral feeding Fasting in anticipation of Increase in subsequent feeding rate to compensate for the missed volume diagnostic or surgical procedure (Additional) parenteral feeding Airway tube management Continuous transpyloric feeding [20] Increase in subsequent feeding rate to compensate for the missed volume (Additional) parenteral feeding Material related2 Pro-active approach of medical personnel

1 For example: vomiting, nausea, retentions, diarrhea, abdominal pain. 2 For example: gastric tube occlusion or displacement, electric pump dysfunction, absence of venous access, administration of medication that interferes with enteral feeding, and the administration of medication over the same venous catheter.

Timing of Nutritional Support Postpyloric as opposed to gastric tube place- Nutritional support should be started within the ment is associated with reduced gastric residual first 24 h from admission to the ICU in children volume and reflux, but adequately powered trials who are hemodynamically stable and have a are not available to support prevention of aspira- functioning gastrointestinal tract. tion pneumonia. 3 Route of Nutritional Support Type of Formula Enteral nutrition (EN) via tube feeding is the pre- There are no studies available that support the ferred method of feeding the critically ill patient. clinical advantage of oligomeric formulas in crit- EN reverses the loss of gastrointestinal mucosal ically ill children instead of polymeric formulas integrity, maintains intestinal blood flow, pre- (see Chapter 3.3). There is no evidence as yet on serves IgA-dependent immunity, and contributes the use of immune-modulating formulas, e.g. to the maintenance of the host immune response. formulas enriched with glutamine, arginine or Meta-analyses of clinical studies have reported nucleotides, in the critically ill child. This can be that EN as opposed to parenteral nutrition is as- considered in burn injury and trauma patients. sociated with a lower risk of infection and also cost savings [16]. Compliance Total or additional parenteral nutrition (PN) It is important to realize that large discrepancies is recommended when contraindications for EN may arise between prescribed and delivered or exist, or when patients cannot be fed sufficiently prescribed and required nutrients due to inade- via the enteral route within the first few days of quate delivery or poor compliance [17] . The main ICU stay (see figure 1 for these conditions). reasons for inadequate delivery of nutrients can be divided into four groups which are shown in

Intensive Care 251 Initial assessment of critically ill children on admission to the ICU Nutritional status: weight, length, MUAC Primary diagnosis Illness severity Measurement of energy expenditure (if possible)

Start glucose infusion 4–8 mg/kg per min

Yes Hemodynamic instability or Start PN within 48 h after admission contraindication for EN*

Reconsider starting EN daily Start EN within 24 h after admission according to MEE or prediction equation or <1 year 50 kcal/kg 1–6 years 45 kcal/kg 7–12 years 35 kcal/kg >12 years 25 kcal/kg

Yes Add additional PN in order to meet Gastrointestinal problems? Only inadequate requirements amounts of EN reached on days 2 or 3? Try to increase EN in the following days and try to reach complete EN No

Increase EN: 2 × MEE (if indirect calorimetry is performed) or <1 year 100 kcal/kg 1–6 years 90 kcal/kg 7–12 years 70 kcal/kg >12 years 50 kcal/kg

During admission: 1 Adjust energy intake according to measurement of energy expenditure and RQ, daily if possible When RQ >1, decrease energy intake by 20%; when RQ <0.85, increase energy intake by 10–20% 2 Daily assess differences between prescribed and delivered nutrients and actively try to prevent these deficits 3 Weekly nutritional assessment (minimum): weight, MUAC; if decrease in nutritional parameters, increase intake by 20%

Fig. 1. Nutritional strategy in pediatric intensive care patients. MUAC = Mid upper arm circumference; EN = enteral nutrition; PN = parenteral nutrition; RQ = respiratory quotient; MEE = measured energy expenditure. * Contraindications for EN: serious gastrointestinal difficulties; congenital anomalies of the gastrointestinal tract; surgery to the gastrointestinal system; short bowel disease; hemodynamic instability; asphyxia.

table 5 . Recommendations for the prevention of Follow-Up of Nutritional Support noncompliance are given. Furthermore, it is nec- Once nutritional support is started, its adequacy essary to compare delivered intake with pre- may be assessed by parameters of nutritional sta- scribed intake on a daily basis. tus, such as anthropometric measurements and indirect calorimetry. The minimum standard for

252 Pediatric Nutrition in Practice nutritional assessment should include measure- • Should generally be administered within the ments of weight, mid upper arm circumference first 24 h following admission and possibly length and indirect calorimetry (EE • Consists of enteral feeding, administered ei- and RQ). ther by the gastric or transpyloric route, un- An overall practical nutritional guideline is less a contraindication for enteral feeding is shown in figure 1. present, or adequate amounts of enteral feeding are not reached within the first few days of intensive care unit stay C o n c l u s i o n s • Must consist of a condensed formula in patients with fluid restriction Nutritional support in the critically ill child: • Must be followed up concerning the delivery • Is an essential aspect of clinical management of nutrients, achieved nutritional status, and and should be integrated in daily care changes in energy need during admission

References

1 Chwals WJ: Overfeeding the critically 9 Phillips R, Ott L, Young B, Walsh J: Nu- sis of agreement between indirect calo- ill child: fact or fantasy? New Horiz tritional support and measured energy rimetry and prediction equations using

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2 Pollack M, Ruttimann U, Wiley J: Nu- with head injury. J Neurosurg 1987; 67: 32: 335–342. tritional depletions in critically ill chil- 846–851. 16 Petros S, Engelmann L: Enteral nutri- dren: associations with physiologic 10 Schofield W: Predicting basal metabol- tion delivery and energy expenditure in instability and increased quantity of ic rate, new standards and review of medical intensive care patients. Clin

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1985; 9: 309–313. 1985; 39: 5–41. 17 Rogers EJ, Gilbertson HR, Heine RG, 3 Hulst J, Joosten K, Zimmermann L, et 11 van Goudoever JB, Sulkers EJ, Lafeber Henning R: Barriers to adequate nutri- al: Malnutrition in critically ill chil- HN, Sauer PJ: Short-term growth and tion in critically ill children. Nutrition

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discharge. Clin Nutr 2004; 23: 223–232. infants fed formulas with different en- 18 Koletzko B, Goulet O, Hunt J, et al: 1. 3

4 Klein GL, Herndon DN: Burns. Pediatr ergy contents. Am J Clin Nutr 2000; 71: Guidelines on Paediatric Parenteral

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Am J Clin Nutr 2004; 79: 613–618. 13 Coss-Bu JA, Klish WJ, Walding D, et al: by the European Society of Paediatric 6 van den Berghe G, Wouters P, Weekers Energy metabolism, nitrogen balance, Research (ESPR). J Pediatr Gastroen-

F, et al: Intensive insulin therapy in the and substrate utilization in critically ill terol Nutr 2005; 41(suppl 2):S1–S87.

critically ill patients. N Engl J Med children. Am J Clin Nutr 2001; 74: 664– 19 Williams GJ, Herndon DN: Modulating

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7 Dickerson RN, Gervasio JM, Riley ML, 14 Van den Berghe G, Wilmer A, Hermans injuries. J Wound Care 2002; 11: 87–89. et al: Accuracy of predictive methods to G, et al: Intensive insulin therapy in the 20 Lyons KA, Brilli RJ, Wieman RA,

estimate resting energy expenditure of medical ICU. N Engl J Med 2006; 354: Jacobs BR: Continuation of transpyloric thermally-injured patients. JPEN J 449–461. feeding during weaning of mechanical

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Hazelzet JA: Indirect calorimetry in ture in severely burned children: analy- al. JPEN J Parenter Enteral Nutr 2002;

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Intensive Care 253 Koletzko B. (ed): Pediatric Nutrition in Practice. Basel, Karger, 2008, pp 254–269

4 Annex

4.1 The WHO Child Growth Standards Mercedes de Onis

Key Words The full set of tables and charts is presented on the WHO website (www.who.int/childgrowth/ ؒ Growth standards ؒ Growth references Nutritional status ؒ Anthropometry ؒ Nutritional en), together with tools such as software and assessment training materials that facilitate their clinical application. The disjunction observed at 24 months in the length/height-based charts represents the Key Messages change from measuring recumbent length to R Growth assessment is a key screening tool to assess standing height. Standards for other anthropo- child health and nutritional wellbeing metric variables (i.e. mid upper arm circumfer- R Anthropometry is the most universally applicable, ence, and triceps and subscapular skinfolds) are noninvasive method to assess the growth status of children also available in the website. R The interpretation of the growth trajectory is highly dependent on the growth charts used R The WHO Child Growth Standards, based on the Introduction physiological growth of healthy breastfed infants, are the growth charts recommended by WHO for Assessing childhood growth remains a mainstay universal application R Anthropometric measurements need to be accu- of pediatric care in all settings, from the most rate. Adequate equipment and the use of standard- advanced healthcare centers to those faced with ized techniques are essential for reducing mea- severe resource constraints. If adequate growth is surement error and minimizing bias achieved, the probability is high that children Copyright © 2008 S. Karger AG, Basel will be healthy and well-nourished. The docu- mentation of abnormal growth, on the other hand, signals that something is not going well and flags the need for careful diagnostic follow- This Annex presents growth charts for up and action. The value of growth assessment is • weight-for-age thus its principal utility as a key screening tool • length/height-for-age to assess children’s general wellbeing, identify • weight-for-length/height growth faltering and excessive growth, evaluate • body mass index-for-age maternal lactation performance and infant feed- • head circumference-for-age ing practices, and monitor children with medical in percentile values for boys and girls aged 0–60 conditions known to adversely affect growth, months. such as renal and cardiac conditions. Growth assessment is best done by the appro- of a standard as opposed to a reference merely priate use and interpretation of anthropometric describing how children grew in a particular indexes [1] . Anthropometry is the single most place and time. Although standards and refer- universally applicable, inexpensive, and nonin- ences both serve as a basis for comparison, each vasive method available to assess the proportions, enables a different interpretation. Since a stan- size, and composition of the human body. The dard defines how children should grow, devia- successful assessment of growth using anthro- tions from the pattern it describes are evidence of pometry is founded on (a) the selection of an ap- abnormal growth. A reference, on the other hand, propriate anthropometric indicator, (b) the accu- does not provide as sound a basis for such value racy and reliability of the anthropometric mea- judgments, although in practice references often sures taken, and (c) the proper interpretation of are mistakenly used as standards. the values by selecting suitable growth charts and Following a Resolution from the World Health cutoffs to assess risk or classify children accord- Assembly in May 1994 endorsing these recom- ing to variable degrees of undernutrition and mendations, the WHO Multicentre Growth Ref- overweight/obesity. erence Study (MGRS) [4] was launched in 1997 to The growth charts presented in this Annex collect primary growth data that would allow the are a subset of the WHO Child Growth Standards construction of new growth charts consistent [2, 3] , which are based on a international sample with ‘best’ health practices. of healthy breastfed infants and young children The goal of the MGRS was to describe the [4] . growth of healthy children. Implemented be- The origin of the WHO Child Growth Stan- tween 1997 and 2003, the MGRS is a population- dards dates back to the early 1990s when WHO based study conducted in six countries from di- initiated a comprehensive review of the uses and verse geographical regions: Brazil, Ghana, India, interpretation of anthropometric references. This Norway, Oman, and the USA [4] . The study com- analysis showed that the growth pattern of bined a longitudinal follow-up from birth to 24 healthy breastfed infants deviated to a significant months with a cross-sectional component of chil- extent from the NCHS/WHO international refer- dren aged 18–71 months. In the longitudinal ence [5] . The expert group concluded from these component, mothers and newborns were en- and other related findings that the NCHS/WHO rolled at birth and visited at home a total of 21 reference did not adequately describe the physi- times at weeks 1, 2, 4 and 6; monthly from 2–12 ological growth of children and that its use to months; and bimonthly in the second year. monitor the health and nutrition of individual The study populations lived in socioeconom- children or to derive estimates of child malnutri- ic conditions favorable to growth. The individu- tion in populations was flawed. In particular, the al inclusion criteria were: no known health or reference was inadequate for assessing the growth environmental constraints to growth, mothers 4 pattern of healthy breastfed infants because it willing to follow MGRS feeding recommenda- was based on predominantly formula-fed infants, tions (i.e. exclusive or predominant breastfeed- as are most national growth charts in use today. ing for at least 4 months, introduction of com- The group recommended the development of plementary foods by 6 months of age, and con- new standards, adopting a novel approach that tinued breastfeeding to at least 12 months of would describe how children should grow when age), no maternal smoking before and after de- free of disease and when their care follows healthy livery, single term birth, and absence of signifi- practices such as breastfeeding and non-smoking cant morbidity. Rigorously standardized meth- [6] . This approach would permit the development ods of data collection and procedures for data

The WHO Child Growth Standards 255 management across sites yielded high-quality that healthy children from around the world who data. are raised in healthy environments and follow The length of children was strikingly similar recommended feeding practices have strikingly among the six sites, with only about 3% of vari- similar patterns of growth [7] . The International ability in length being due to inter-site differenc- Pediatric Association has officially endorsed the es compared to 70% for individuals within sites use of the WHO standards describing them as ‘an [7] . The striking similarity in growth during ear- effective tool for detecting both undernutrition ly childhood across human populations means and obesity, thus addressing the double burden of either a recent common origin as some suggest malnutrition affecting populations on a global [8] or a strong selective advantage associated with basis’ [10] . the current pattern of growth and development Note: WHO holds copyright of the WHO across human environments. Child Growth Standards. Of 1,743 mother–child dyads enrolled in the MGRS longitudinal sample, 882 complied with the study’s infant-feeding and non-smoking cri- C o n c l u s i o n s teria and completed the follow-up period of 24 months. The compliant sample was used to con- Early recognition of growth problems, such as struct the WHO standards from birth to 2 years growth faltering and excessive weight gain rela- of age combined with 6,669 children from the tive to linear growth, should become standard cross-sectional sample from age 2 to 5 years [9] . clinical practice by: Data from all sites were pooled to construct the • The routine collection of accurate weight and standards [7] . The generation of the standards height measurements to enable monitoring of followed state-of-the-art statistical methodolo- childhood growth gies [2, 3] . The concordance between the smoothed • The interpretation of anthropometric indices, curves and empirical percentiles was excellent such as height-for-age and BMI-for-age, based and free of bias at both the median and the edges, on the WHO Child Growth Standards indicating that the resulting curves are a fair de- • The early intervention after changes on growth scription of physiological growth of healthy chil- patterns (e.g., upward or downward crossing dren [2] . of percentiles) have been observed to provide parents and caregivers appropriate guidance and support C o n c l u d i n g R e m a r k s

The WHO Child Growth Standards were derived from children who were raised in environments that minimized constraints to growth such as poor diets and infection. In addition, their mothers followed healthy practices such as breastfeeding their children and not smoking during and after pregnancy. The standards depict normal human growth under optimal environmental conditions and can be used to assess children ev- erywhere, regardless of ethnicity, socioeconomic status and type of feeding. They also demonstrate

256 Pediatric Nutrition in Practice References

1 WHO: Physical status: the use and in- 4 de Onis M, Garza C, Victora CG, et al 8 Rosenberg NA, Pritchard JK, Weber JL, terpretation of anthropometry. Report (eds): WHO Multicentre Growth Refer- et al: Genetic structure of human popu-

of a WHO Expert Committee. World ence Study (MGRS): rationale, plan- lations. Science 2002; 298: 2381–2385.

Health Organ Tech Rep Ser 1995; 854: ning and implementation. Food Nutr 9 WHO Multicentre Growth Reference

161–262. Bull 2004; 25(suppl 1):S1–S89. Study Group: Enrolment and baseline 2 WHO Multicentre Growth Reference 5 WHO Working Group on Infant characteristics in the WHO Multicentre Study Group: WHO Child Growth Stan- Growth: An evaluation of infant Growth Reference Study. Acta Paediatr

dards: Length/Height-for-Age, Weight- growth: the use and interpretation of Suppl 2006; 450: 7–15. for-Age, Weight-for-Length, Weight- anthropometry in infants. Bull World 10 International Pediatric Association:

for-Height and Body Mass Health Organ 1995; 73: 165–174. Endorsement of the New WHO Growth Index-for-Age: Methods and Develop- 6 Garza C, de Onis M; WHO Multicentre Standards for Infants and Young Chil- ment. Geneva, WHO, 2006. Growth Reference Study Group: Ratio- dren. http://www.who.int/childgrowth/ 3 WHO Multicentre Growth Reference nale for developing a new international Endorsement_IPA.pdf.

Study Group: WHO Child Growth Stan- growth reference. Food Nutr Bull 2004; dards based on length/height, weight 25(suppl 1):S5–S14.

and age. Acta Paediatr Suppl 2006; 450: 7 WHO Multicentre Growth Reference 76–85. Study Group: Assessment of differences in linear growth among populations in the WHO Multicentre Growth Refer-

ence Study. Acta Paediatr Suppl 2006;

450: 56–65.

The WHO Child Growth Standards 257 258 Pediatric Nutrition in Practice 4

The WHO Child Growth Standards 259 260 Pediatric Nutrition in Practice 4

The WHO Child Growth Standards 261 262 Pediatric Nutrition in Practice 4

The WHO Child Growth Standards 263 264 Pediatric Nutrition in Practice 4

The WHO Child Growth Standards 265 266 Pediatric Nutrition in Practice 4

The WHO Child Growth Standards 267 268 Pediatric Nutrition in Practice 4

The WHO Child Growth Standards 269 Koletzko B. (ed): Pediatric Nutrition in Practice. Basel, Karger, 2008, pp 271–284

4 Annex

4.2 The CDC and Euro Growth Charts Ekhard Ziegler

Key Words ative position of a child undergoing assessment Growth assessment ؒ Growth references ؒ in comparison with reference data determines Anthropometry ؒ Interpretation whether the child’s growth is judged normal or abnormal. Widely used growth references are the CDC Growth Charts [1] and the Euro-Growth Key Messages Charts [2] . Both were released in 2000. In spite of R Growth charts are essential tools for the interpreta- minor exceptions in the case of the CDC charts, tion of growth measurements in children these charts essentially describe the growth of all R Growth references (examples: CDC, Euro-Growth) children living, respectively, in the United States describe the growth of populations of children as and Europe. This sets them apart from the WHO they exist at a given time in a given location R Growth standards (example: WHO Child Growth Growth Standards [3, 4], which describe the Standards) describe the growth of children who growth of children worldwide who live in favor- live in favorable circumstances, receive optimal nu- able circumstances, receive optimal nutrition trition and show desirable growth characteristics and show desirable growth characteristics. The R Anthropometric measurements need to use prop- distinction between references and standards has er techniques. Measurements of recumbent length must be interpreted against charts of recumbent implications for the use of growth charts. Where- length, and measurements of standing height as the use of references requires some element of must be interpreted against charts of standing judgment on the part of the user, the use of stan- height Copyright © 2008 S. Karger AG, Basel dards is inherently simpler as it requires little or no judgment on the part of the user. 4 Introduction The CDC Growth Charts: United States

Growth assessment is an integral part of child- The CDC charts [1] were created to replace the hood health monitoring. For interpretation, widely used NCHS/WHO charts because of inad- growth measurements must be compared to ap- equacies identified in the latter. The CDC charts propriate norms. Such norms have traditionally are based on a large number of nationally repre- been provided by growth references which de- sentative data from various national surveys con- scribe the growth of children living in a defined ducted between 1976 and 1994. The exception are geographic area who are deemed healthy. The rel- data for the first year of life, which are few in number and were obtained partly from infants ence simply describes what exists and therefore representing lower socioeconomic strata. Also, leaves it up to the user to judge whether a given data for subjects 1 6 years of age from the most child’s growth is normal, or healthy, or neither. A recent national survey (1988–1994) were exclud- standard, on the other hand, already incorpo- ed because of the increased prevalence of high rates a large element of judgment and requires weight in that sample. The data were strictly little if any judgment from the user. This would cross-sectional. State-of-the-art smoothing pro- seem to be a distinct advantage when charts are cedures were used to generate centile curves. For used by untrained observers who lack the ability birth to 3 years charts for weight for age and (re- to render judgments. cumbent) length for age are available. For ages 2–20 years charts for weight for age, height for age and body mass index are available. General Comment on Growth Assessment

The importance of using proper measurement The Euro-Growth Charts techniques cannot be overemphasized. In particular measurements of recumbent length are dif- The Euro-Growth charts [2] were the result of a ficult to perform and require specific equipment, multinational effort. Data for these charts were training and effort if reproducible measurements gathered from birth to 5 years of age in children are to be obtained. Measurements of length must who were born between 1990 and 1993 and lived be interpreted using charts for length, and mea- close to 22 measurement sites in 11 European surements of height must be interpreted using countries. Data were gathered longitudinally, charts for height. The distinction is important with 1,746 children being followed to age 1 year, largely in the overlap area between 1 and 3 years 1,071 to age 3 years and 571 to age 5 years. Data of age. were analyzed cross-sectionally using state-of- Single measurements of growth are subject to the art smoothing techniques. error due to multiple sources. Erroneous mea- Euro-Growth provides a software (www. surements can lead to grossly erroneous judg- Euro-Growth.org), which calculates weight and ments regarding the growth of a child. The accu- length gains and raises a warning flag if gain of racy of growth assessments is greatly improved if an infant is outside the 8 2SD range. Z scores two ore more measurements are performed at can be calculated and growth references can be different times. This not only minimizes the im- corrected for parental height, gestational age, and pact of the errors of single measurements, it also duration of exclusive breastfeeding. permits an assessment of time trends and thus strengthens the assessment of a child’s growth vis-à-vis the growth reference or standard. C o m m e n t

In contradistinction to the recently published C o n c l u s i o n s WHO Growth Standards [3, 4], the CDC charts and the Euro-Growth charts are growth refer- • Growth monitoring, an essential part of child- ences. They represent, with minor exceptions, hood health maintenance, requires accurate the growth of healthy children living in the re- anthropometric measurements and interpre- spective geographic areas. The distinction is im- tation of growth measurements with the help portant to the user of the charts. A growth refer- of growth charts

272 Pediatric Nutrition in Practice • If reference charts are used, such as the CDC • The use of growth standards, such as the Charts or the Euro-Growth Charts, a certain WHO Growth Standards, on the other hand, amount of judgment is required on the part of requires relatively little judgment on the part the user for proper interpretation of measure- of the user ments

References

1 Kuczmarski RJ, Ogden CL, Guo SS, 2 Haschke F, van’t Hof MA (eds): Euro- 4 WHO Multicentre Growth Reference Grummer-Strawn LM, Flegal KM, Mei Growth. J Pediatr Gastroenterol Nutr Study Group: WHO Child Growth Stan-

Z, Wei R, Curtin LR, Roche AF, John- 2000; 31:suppl 1. dards based on length/height, weight

son CL: 2000 CDC growth charts for 3 WHO Multicentre Growth Reference and age. Acta Paediatr Suppl 2006; 450: the United States: Methods and devel- Study Group: WHO Child Growth Stan- 76–85.

opment. Vital Health Stat 11, 2000; 246: dards. Geneva, WHO, 2006. www.who. 1–190. int/childgrowth/en/

The CDC and Euro Growth Charts 273 Fig. 1. CDC length-for-age and weight-for-age for boys birth to 3 years.

274 Pediatric Nutrition in Practice 4

Fig. 2. CDC length-for-age and weight-for-age for girls birth to 3 years.

The CDC and Euro Growth Charts 275 Fig. 3. CDC stature-for-age and weight-for-age for boys 2–20 years.

276 Pediatric Nutrition in Practice 4

Fig. 4. CDC stature-for-age and weight-for-age for girls 2–20 years.

The CDC and Euro Growth Charts 277 Fig. 5. CDC body mass index-for-age for boys 2–20 years.

278 Pediatric Nutrition in Practice 4

Fig. 6. CDC body mass index-for-age for girls 2–20 years.

The CDC and Euro Growth Charts 279 cm P95 95.0

90.0 P50

85.0 P5

80.0

75.0

70.0

65.0

60.0

55.0

50.0

45.0

40.0 0 48121620 24 28 a Age (months) www.euro-growth.org

cm 120.0 P95

115.0

110.0 P50

105.0 P5 100.0

95.0

90.0

85.0

80.0

75.0

70.0

65.0

60.0 24 30 36 42 48 54 60 b Age (months) www.euro-growth.org

Fig. 7. a Euro-Growth length-for-age for boys birth to 2 years. b Euro-Growth height-for-age for boys 2–5 years.

280 Pediatric Nutrition in Practice cm

95.0 P95

90.0 P50

85.0 P5

80.0

75.0

70.0

65.0

60.0

55.0

50.0

45.0

40.0 0481216 20 24 28 a Age (months) www.euro-growth.org

120.0 P95

115.0

110.0 P50

105.0 P5 100.0

95.0

90.0

85.0 80.0 4 75.0

70.0

65.0

60.0 24 30 36 42 48 54 60 b Age (months) www.euro-growth.org

Fig. 8. a Euro-Growth length-for-age for girls birth to 2 years. b Euro-Growth height-for-age for girls 2–5 years.

The CDC and Euro Growth Charts 281 BMI

20.0

P95

18.0

P50 16.0

P5 14.0

12.0

10.0 04 81216 20 24 28 a Age (months) www.euro-growth.org

BMI

19.0 P95

18.0

17.0

16.0

P50

15.0

14.0

P5 13.0

12.0 24 30 36 42 48 54 60 b Age (months) www.euro-growth.org

Fig. 9. a Euro-Growth body mass index for boys birth to 2 years. b Euro-Growth body mass index for boys 2–5 years.

282 Pediatric Nutrition in Practice BMI

20.0

P95

18.0

16.0 P50

14.0 P5

12.0

10.0 0481216 20 24 28 a Age (months) www.euro-growth.org

BMI

20.0 P95

18.0

16.0 P50 4 14.0

12.0 24 30 36 42 48 54 60 b Age (months) www.euro-growth.org

Fig. 10. a Euro-Growth body mass index for girls birth to 2 years. b Euro-Growth body mass index for girls 2–5 years.

The CDC and Euro Growth Charts 283 grams P95 24,000

22,000

20,000 P50 18,000

16,000 P5 14,000

12,000

10,000

8,000

6,000

4,000

2,000

0 0 6 12 18 24 30 36 42 48 54 60 Age (months) www.euro-growth.org-

Fig. 11. Euro-Growth weight-for-age for boys birth to 5 years.

grams 28,000

26,000 P95

24,000

22,000

20,000 P50 18,000

16,000 P5 14,000

12,000

10,000

8,000

6,000

4,000

2,000

0 0 6 12 18 24 30 3642 48 54 60 Age (months) www.euro-growth.org-

Fig. 12. Euro-Growth weight-for-age for girls birth to 5 years.

284 Pediatric Nutrition in Practice Koletzko B. (ed): Pediatric Nutrition in Practice. Basel, Karger, 2008, pp 285–292

4 Annex

4.3 Reference Nutrient Intakes for Infants, Children and Adolescents Berthold Koletzko ؒ Maria Hermoso

Tables with reference nutrient intakes are pre- Tables 1 and 2. Australia and New Zealand nutrient ref- sented as published by (in alphabetical order) erence values for diary food energy (table 1) and nutrients (table 2) in healthy infants, children and adoles- Australia and New Zealand; Germany, Austria cents (modified from nutrient reference values includ- and Switzerland; the Nordic nutrition recom- ing recommended dietary intakes from Australia and mendations; United Kingdom; United States and New Zealand 2005) Canada; World Health Organization (WHO) with the Food and Agriculture Organization Table 1. Energy (male/female) (FAO) and the United Nations University Age Energy Age Energy (UNU). months kJ/day years MJ/day

1 2,000/1,800 3 3.4/3.2 2 2,400/2,100 4 3.6/3.4 Acknowledgement 3 2,400/2,200 5 3.8/3.6 4 2,400/2,200 6 4.1/3.8 The authors’ work in this area is carried out with partial 5 2,500/2,300 7 4.3/4.0 financial support from the Commission of the European 6 2,700/2,500 8 4.5/4.2 Communities, specific RTD Programme ‘Food Quality 7 2,800/2,500 9 4.8/4.5 and Safety – Integrating and Strengthening the Europe- 8 3,000/2,700 10 5.1/4.7 an Research Area’, within the 6th Framework Pro- 9 3,100/2,800 11 5.4/4.9 gramme, research contract No. FP6-036196-2 (Aligning 10 3,300/3,000 12 5.8/5.2 nutrient recommendations across Europe with special 11 3,400/3,100 13 6.2/5.5 focus on vulnerable groups and consumer understand- 12 3,500/3,200 14 6.6/5.7 ing – EURRECA). This chapter does not necessarily re- 15 3,800/3,500 15 7.0/5.8 flect the views of the Commission and in no way antici- 18 4,000/3,800 16 7.3/5.9 pates future policy in this area. 4 21 4,200/4,000 17 7.6/5.9 24 4,400/4,200 18 7.7/6.0 Table 2. Nutrient values (male/female)

Age Total n-6 poly- n-3 poly- Total LCn-3 Calcium Magnesium fat unsaturated unsaturated (DHA+EPA+ mg mg g/day fats, g/day fats, g/day DPA), mg/day

0–6 months 31 4.4 0.5 210 30 7–12 months 30 4.6 0.5 270 75 1–3 years 5 0.5 40 500 80 4–8 years 8 0.8 55 700 230 9–13 years 10/8 1.0/0.8 70 1,000 (9–11 years) 240 1,300 (12–13 years) 14–18 years 12/8 1.2/0.8 125/85 1,300 410/360

Age Iron Iodine Zinc Vit. A, mg retinol Vit. D Vit. K mg/day ␮g/day mg/day equivalent/day ␮g/day ␮g/day

0–6 months 0.2 90 2.0 250 (retinyl esters) 5.0 2.0 7–12 months 11 110 3 430 5.0 2.5 1–3 years 9 90 3 300 5.0 25 4–8 years 10 90 4 400 5.0 35 9–13 years 8 120 6 600 5.0 45 14–18 years 11/15 150 13/7 900/700 5.0 55

Age Thiamine Riboflavin Niacin Vit. B6 Folate Vit. B12 Vit. C mg/day mg/day mg niacin mg/day ␮g dietary ␮g/day mg/day equivalent/day folate equivalents/day

0–6 months 0.2 0.3 2 (preformed 0.1 65 (folate) 0.4 25 niacine) 7–12 months 0.3 0.4 4 0.3 80 0.5 30 1–3 years 0.5 0.5 6 0.5 150 0.9 35 4–8 years 0.6 0.6 8 0.6 200 1.2 35 9–13 years 0.9 0.9 12 1.0 300 1.8 40 14–18 years 1.2/1.1 1.3/1.1 16/14 1.3/1.2 400 2.4 40

286 Pediatric Nutrition in Practice Table 3. German, Austrian and Swiss reference values (male/female) for the average daily energy and nutrient intakes in populations of healthy children and adolescents (modified from reference intakes for Germany, Austria and Swit- zerland 2002)

Age Energy Protein Fat Essential Calcium Magnesium kcal/kg/day g/kg/day % of energy fatty acids mg/day mg/day % of energy

0–<4 months 110 2.0–2.2 45–50 4.5 500 40 4–<12 months 95 1.2–1.6 35–40 3.8 500 60 1–<4 years 100 1.2 30–35 3.0 600 80 4–<7 years 90 1.1 30–35 3.5 700 120 7–<10 years 75 1.0 30–35 3.5 800 170 10–<13 years 60/55 1.0 30–35 3.5 900 230/250 13–<15 years 55/45 1.0 30–35 3.5 1,000 310 15–<19 years 45/40 0.9/0.8 30–35 3.5 1,200 400/350

Age Iron Iodine Zinc Vit. A Vit. D Vit. K mg/day ␮g/day mg/day mg retinol ␮g/day ␮g/day equivalent/day

0–<4 months 6 50 5 0.5 10 5 4–<12 months 8 80 5 0.6 10 10 1–<4 years 8 100 7 0.6 5 15 4–<7 years 8 120 10 0.7 5 20 7–<10 years 10 140 11 0.8 5 30 10–<13 years 12/15 180 12 0.9 5 40 13–<15 years 12/15 200 15/12 1.1/1.0 5 50 15–<19 years 12/15 200 15/12 1.1/0.9 5 70/60

Age Thiamine Riboflavin Niacin Vit. B6 Folate Vit. B12 Vit. C mg/day mg/day mg niacin mg/day ␮g dietary ␮g/day mg/day equivalent/day folate equivalents/day

0–<4 months 0.3 0.3 5 0.3 80 0.5 40 4–<12 months 0.4 0.5 6 0.6 80 0.8 50 1–<4 years 0.7 0.8 9 0.9 120 1.0 55 4–<7 years 1.0 1.1 12 1.2 160 1.5 60 7–<10 years 1.1 1.2 13 1.4 200 1.8 65 10–<13 years 1.2 1.4/1.3 15/14 1.6/1.5 240 2.0 70 13–<15 years 1.4/1.2 1.5/1.4 17/15 1.8/1.6 300 3.0 75 15–<19 years 1.6/1.3 1.8/1.7 20/16 2.1/1.8 300–400 3.0 75 4

Reference Nutrient Intakes of Infants, Children and Adolescents 287 Table 4. Nordic nutrition recommendation intake values (male/female) for diary energy intake and nutrients intake for healthy infants, children and adolescents (adapted from the Nordic nutrition recommendations 2004: Norway, Sweden, Finland, Denmark, Iceland)

Age Energy Protein Fat Essential fatty acids, Calcium Magnesium MJ/day % of energy % of % of energy mg/day mg/day energy n-6 n-3

<6 months – – – 6–11 months 3.2 7–15 30–45 4 1 540 80 12–23 months 4.1 10–15 3 0.5 600 85 2–5 years 5.3 30–35 600 120 6–9 years 7.7 700 200 10–13 years 9.8/8.6 900 280 14–17 years 12.3/9.6 900 350/280

Age Iron Iodine Zinc Vit. A, mg retinol Vit. D Vit. K mg/day ␮g/day mg/day equivalent/day ␮g/day ␮g/day

<6 months – – – – – – 6–11 months 8 50 5 300 10 – 12–23 months 8 70 5 300 10 – 2–5 years 8 90 6 350 7.5 – 6–9 years 9 120 7 400 7.5 – 10–13 years 11 150 11/8 600 7.5 – 14–17 years 11/15 150 12/11 900/700 7.5 –

Age Thiamine Riboflavin Niacin Vit. B6 Folate Vit. B12 Vit. C mg/day mg/day mg niacin mg/day ␮g dietary folate ␮g/day mg/day equivalent/day equivalents/day

<6 months – – – – – – – 6–11 months 0.4 0.5 5 0.4 50 0.5 20 12–23 months 0.5 0.6 7 0.5 60 0.6 25 2–5 years 0.6 0.7 9 0.7 80 0.8 30 6–9 years 0.9 1.1 12 1.0 130 1.3 40 10–13 years 1.2/1.0 1.4/1.2 16/14 1.3/1.1 200 2.0 50 14–17 years 1.5/1.2 1.7/1.3 20/15 1.6/1.3 300 2.0 75

288 Pediatric Nutrition in Practice Table 5. United Kingdom dietary reference values (male/female) for diary food energy and nutrients of healthy infants, children and adolescents in the UK (modified from reference intakes in UK 1991)

Age Energy Protein Fat, % of Essential fatty Calcium Magnesium kcal/kg/day g/kg/day energy acids % of energy mg/day mg/day

0–<3 months 545/515 12.5 – – 525 55 4–<6 months 690/645 12.7 – – 525 60 7–<9 months 825/765 13.7 – – 525 75 10–<12 months 920/865 14.9 – – 525 80 1–<3 years 1,230/1,165 14.5 – – 350 85 4–<6 years 1,715/1,545 19.7 – – 450 120 7–<10 years 1,970/1,740 28.3 – – 550 200 11–<14 years 2,220/1,845 42.1/41.2 – – 1,000/800 280 15–<19 years 2,755/2,110 55.2/45.0 – – 1,000/800 300

Age Iron Iodine Zinc Vit. A, mg retinol Vit. D Vit. K mg/day ␮g/day mg/day equivalent/day ␮g/day ␮g/day

0–<3 months 1.7 50 4.0 350 8.5 – 4–<6 months 4.3 60 4.0 350 8.5 – 7–<9 months 7.8 60 5.0 350 7 – 10–<12 months 7.8 60 5.0 350 7 – 1–<3 years 6.9 70 5.0 400 7 – 4–<6 years 6.1 100 6.5 400 – – 7–<10 years 8.7 110 7.0 500 – – 11–<14 years 11.3/14.8 130 9.0 300/600 – – 15–<19 years 11.3/14.8 140 9.5/7.0 700/600 – –

Age Thiamine Riboflavin Niacin Vit. B6 Folate Vit. B12 Vit. C mg/day mg/day g niacin mg/day ␮g dietary folate ␮g/day mg/day equivalent/day equivalents/day

0–<3 months 0.2 0.4 3 0.2 50 0.3 25 4–<6 months 0.2 0.4 3 0.2 50 0.3 25 7–<9 months 0.2 0.4 4 0.3 50 0.4 25 10–<12 months 0.3 0.4 5 0.4 50 0.4 25 1–<3 years 0.5 0.6 8 0.7 70 0.5 30 4–<6 years 0.7 0.8 11 0.9 100 0.8 30 7–<10 years 0.7 1.0 12 1.0 150 1.0 30 11–<14 years 0.9/0.7 1.2/1.1 15/12 1.2/1.0 200 1.2 35 15–<19 years 1.1/0.8 1.3/1.1 18/14 1.5/1.2 200 1.5 40 4

Reference Nutrient Intakes of Infants, Children and Adolescents 289 Tables 6 and 7. United States and Canada dietary reference intakes (male/female) for infants, children and adolescents (modified from dietary reference intakes from the United States 1997/2000/2005)

Table 6. Energy

Age, months Energy, kcal/day Age, months Energy, kcal/day

1 472/438 11 817/742 2 567/500 12 844/768 3 572/521 15 908/837 4 548/508 18 961/899 5 596/553 21 1,006/952 6 645/593 24 1,050/997 7 668/608 27 1,086/1,033 8 710/643 30 1,121/1,077 9 746/678 33 1,157/1,113 10 793/717 35 1,184/1,139 3–18 years Depends on physical activity level

Table 7. Nutrient values (male/female)

Age Protein Fat Polyunsaturated fatty acids Calcium Magnesium g/day g/day g/day mg/day mg/day n-6 n-3

0–<6 months 9.1 31 4.4 0.5 210 30 7–<12 months 11.0 30 4.6 0.5 270 75 1–<3 years 13 30–40 7 0.7 500 80 4–<8 years 19 25–35 10 0.9 800 130 9–<13 years 34 25–35 12/10 1.2/1.0 1,300 240 14–<18 years 52/46 25–35 16/11 1.6/1.1 1,300 410/360

Age Iron Iodine Zinc Vit. A, mg retinol Vit. D Vit. K mg/day ␮g/day mg/day equivalent/day ␮g/day ␮g/day

0–<6 months 0.27 110 2 400 5 2 7–<12 months 11 130 3 500 5 2.5 1–<3 years 7 90 3 300 5 30 4–<8 years 10 90 5 400 5 55 9–<13 years 8 120 8 600 5 60 14–<18 years 11/15 150 11/9 900/700 5 75

Age Thiamine Riboflavin Niacin, mg niacin Vit. B6 Folate, ␮g total Vit. B12 Vit. C mg/day mg/day equivalent/day mg/day folate/day ␮g/day mg/day

0–<6 months 0.2 0.3 2 0.1 65 0.4 40 7–<12 months 0.3 0.4 4 0.3 80 0.5 50 1–<3 years 0.5 0.5 6 0.5 150 0.9 15 4–<8 years 0.6 0.6 8 0.6 200 1.2 25 9–<13 years 0.9 0.9 12 1.0 300 1.8 45 14–<18 years 1.2/1.0 1.3/1.0 16/14 1.3 400 2.4 75/65

290 Pediatric Nutrition in Practice Tables 8–10. WHO/FAO/UNU recommended diary nutrient intake values for infants, children and adolescents (modified from the World Health Organization WHO/Food and Agriculture Organization FAO/United Nations University UNU expert groups 2004, 1994, 1985)

Table 8. Energy, protein and fat (male/female) Table 9. Calcium and magnesium (male/female)

Age Energy Protein Fat % of Age Calcium, mg/day Magnesium, mg/day kcal/day g/day energy 0–6 months 300 (human milk) 26 (human-milk-fed) 3–6 months 700 13 400 (cow’s milk) 36 (formula-fed) 6–9 months 810 14 30–40 7–12 months 400 54 9–12 months 950 14 30–40 1–3 years 500 60 1–2 years 1,150 13.5 30–40 4–6 years 600 76 2–3 years 1,350 15.5 7–9 years 700 100 3–5 years 1,550 17.5 10–18 years 1,300 230/220 5–7 years. 1,850/1,750 21 7–10 years 2,100/1,800 27 10–12 years 2,200/1,950 34/36 12–14 years 2,400/2,650 43/44 14–16 years 2,650/2,150 52/46 16–18 years 2,850/2,150 56/42 For table 10, see next page.

References

Australian Government, Department of World Health Organization: Vitamin and Food and Nutrition Board, Institute of Health and Ageing, National Health Mineral Requirements in Human Nu- Medicine: Dietary Reference Intakes and Medical Research Council: Nutri- trition, ed 2. Geneva, WHO, 2004. (DRIs) for Vitamin C, Vitamin E, Sele- ent Reference Values for Australia and World Health Organization: Report on Diet, nium, and Carotenoids. New Zealand Including Recommended Nutrition, and the Prevention of Food and Nutrition Board, Institute of Dietary Intakes. Sydney, Australian Chronic Diseases. Geneva, WHO, 2003. Medicine, National Academies (1998) Government, Department of Health World Health Organization: Energy and Dietary Reference Intakes for Thiamin, and Ageing, National Health and Medi- Protein Requirements. Geneva, WHO, Riboflavin, Niacin, Vitamin B6, Folate, cal Research Council, 2006. 1985. Vitamin B12, Pantothenic Acid, Biotin, German Nutrition Society (DGE), Austrian World Health Organization: Fat and Oils in and Choline. Washington, National Nutrition Society (OGE), Swiss Society Human Nutrition. Geneva, WHO, 1994. Academies, 2000. for Nutrition Research (SGE), Swiss Food and Nutrition Board, Institute of Food and Nutrition Board, Institute of Nutrition Association (SVE): Referenz- Medicine: Dietary Reference Intakes Medicine: Dietary Reference Intakes werte für die Nahrstoffzufuhr (Refer- (DRIs). Washington, National Acad- for Calcium, Phosphorus, Magnesium, ence Values for Nutrient Intake), ed 1. emies, 1997,1998, 2000, 2005. www. Vitamin D, and Fluoride. Washington, 4 Frankfurt/Main, 2000. nap.edu. National Academies, 1997. Nordic Nutrition Recommendations: Inte- Food and Nutrition Board, Institute of grating Nutrition and Physical Activity, Medicine: Dietary Reference Intakes ed 4. 2004. (DRIs) for Energy, Carbohydrate, Fiber, Department of Health: Dietary Reference Fat, Fatty Acids, Cholesterol, Protein, Values for Food Energy and Nutrients and Amino Acids (Macronutrients). for the United Kingdom (Report on Washington, National Academies, Health and Social Subjects). London, 2005. HMSO, 1991.

Reference Nutrient Intakes of Infants, Children and Adolescents 291 g/ K ␮ day g/ D ␮ day g retinol ␮ Vit. C mg/day A, equivalent/ day low availability 12 g/day Vit. B ␮ moderate availability 4.1 8.4 400 5 10 (formula-fed) g folate (HM-fed) ␮ Zinc, mg/day, depends on: Vitamin 2.25 high availability 3.35.1/4.3 5.6 8.6/7.2 17.1/14.4 11.2 600 500 5 35–55 5 25 Folate, equivalents/day g/day (6–12 years) 150 (13–18 years) 6 mg/day Vit. B 5% bioavailability (11–14 years) 29.2/28.0 (pre-menarche) 65.4 (15–17 years) 37.6/62.0 Niacin, mg niacin equivalent/day 10% bioavailability (11–14 years) 14.6/14.0 (pre-menarche) 32.7 (15–17 years) 18.8/31.0 Riboflavin mg/day 12% bioavailability (11–14 years) 12.2/11.7 (pre-menarche) 27.7 (15–17 years) 15.7/25.8 mg/day 15% bioavailability 9.7/9.3 (pre-menarche) 21.8 (15–17 years) 12.5/20.7 Trace elements and vitamins (male/female) vitamins and elements Trace 0–6 months7–12 months – 6.21–3 years4–6 years7–9 years 3.9 4.2 – 7.7 5.9 4.8 5.3 9.3 – 7.4 5.8 6.3 18.6 8.9 – 11.6 12.6 17.8 90 90 90 0.8 90 120 1.1 2.4 2.9 2.8 4.1 4.8 6.6 8.3 9.6 375 400 450 5 5 5 5 15 20 0–6 months7–12 months1–3 years4–6 years7–9 years 0.2 0.3 0.5 0.6 0.3 0.9 0.4 0.5 0.6 0.9 2 4 6 8 12 0.1 0.3 0.5 0.6 1.0 80 80 150 200 300 0.4 0.7 0.9 1.2 1.8 25 30 30 30 35 Age Iron, mg/day Iodine 10–18 years (11–14 years) Age Thiamine 10–18 years 1.1 1.3/1.0 16 1.3/1.2 330 2.4 40 Table 10.

292 Pediatric Nutrition in Practice Koletzko B. (ed): Pediatric Nutrition in Practice. Basel, Karger, 2008, pp 293–295

4 Annex

4.4 Feeding My Baby – Advice for Families Berthold Koletzko ؒ Katharina Dokoupil

The advice given herein has been compiled for Practical Recommendations for families in an affluent country setting in Europe. Breastfeeding Modification may be necessary for other settings. Whether breastfeeding or infant formula – The baby should be attached to the breast within feeding of the baby not only provides nutrition, it the first hour after birth whenever possible. Par- also comprises tender loving care, attention and ticularly during the first days after birth the closeness. mother should ask for help, support, and practical advice how to position the baby. The child should be turned towards the mother with its Breastfeeding whole body and take not only the nipple but a larger portion of the breast into its mouth. Breast- • Breastfeeding is the natural way of feeding for feeding can also be performed after a cesarean healthy infants section. • Breast milk is easy to digest, always available, To promote the formation of breast milk, the comes at the right feeding temperature, and baby should suckle on both breasts during the carries little infectious risk first days. A larger amount of milk will be pro- • Numerous anti-infective components in breast duced a few days after birth. Temporary supple- milk reduce the infant’s risk of infectious dis- mentary feeding with water or other liquids eases, particularly with respect to diarrhea should only be offered if it is deemed necessary • Breastfeeding encourages close body contact by the pediatrician or the pediatric nurse. between mother and infant The baby should be breastfed whenever it • For most babies full or exclusive breastfeeding wishes to suckle, also at night. In the first weeks offers adequate nutrition during the first 4–6 most infants take 8–12 meals in 24 h. months of life. But even a shorter period of full Breastfeeding promotes the gradual loss of the 4 or exclusive breastfeeding with additional mother’s body weight and the extra body fat supplemental feeding is worthwhile – any stores that were deposited during pregnancy. The breastfeeding is strongly encouraged amount of fat loss increases with the duration of • The introduction of complementary feeds full breastfeeding. Additional active weight re- should not discourage continuation of breast- duction during breastfeeding with use of restric- feeding, rather the infant should continue to tive diets is not recommended because it may be breastfed after the introduction of comple- have undesirable effects on milk composition. mentary feeds. Mother and child decide how Breastfeeding women should consume a var- long to continue breastfeeding ied diet and plenty of liquids. A good supply of Vitamin D, fluor Vit. K Bread + milk Snack Cereal fruit Breast milk pap Snack

or infant formula Bread (follow on formula) Milk cereal pap + milk

Vegetable potatoe meat pap

123456789101112 Age, months

Fig. 1. Feeding concept in the first year of life.

iodine (iodized salt, supplements with 100–150 In infants who are not fully breastfed and who ␮ g/day) and long-chain n-3 fatty acids (200 mg have parents or siblings suffering from allergic DHA/day, provided by 1–2 weekly meals of sea diseases, the pediatrician should be consulted re- fish including fatty fish) is recommended. Breast- garding the use of hydrolyzed infant formula feeding women should refrain from smoking and during the first 6 months of life. consumption of significant amounts of alcoholic Manufacturers’ recommendations should be drinks. Only very few mothers of babies with followed carefully with respect to the preparation proven food intolerances are advised to exclude of bottles. Both too low and too high concentra- allergenic foods from their own diets upon indi- tions of formula milks are detrimental. Milk bot- vidual advice from their pediatrician or dietitian, tles must always be freshly prepared and fed but the use of food exclusion for the prevention of within approximately 2 h. Leftovers should be allergies in infants is not recommended. discarded to prevent the occurrence of bacterial infections. Frozen and then defrosted breast milk must be handled in the same way. It is important Infant Formula to keep bottles and nipples clean and dry. Pow- ered formulas have to be prepared with fresh and If breastfeeding is discontinued before 1 year of clean drinking water. The use of water filters is age, an iron-fortified, commercial infant formula not recommended. If water contains high levels should be used. In the first months of life only of nitrate ( 1 50 mg/l; especially in domestic wells) infant formula should be used, which can be con- or water pipes made of lead are used (in some old tinued throughout the first year of life. Follow-up buildings) bottled water suitable for preparing formulas are only appropriate after complemen- infant formula should be used. The suitability of tary feeds have been introduced into the infant’s water from domestic wells should be assessed in diet. each case.

294 Pediatric Nutrition in Practice Infant formulas based on soy protein and oth- ly intervals, additional meals consisting of cere- er so-called ‘special formulas’ are only indicated als with milk and a fruit-grain pap may be intro- in very few special situations and should only be duced ( fig. 1). From the age of about 10 months used upon the recommendation of a pediatrician. bread (initially soft) may be offered. Gluten-con- Self-prepared bottle feeds from cow’s milk, the taining cereals (wheat, rye, barley, for example in milk of other animals (goat mare, sheep’s milk) porridge, bread, biscuits and rusks) should ini- and other sources (such as almond milk) pose se- tially be given only in small quantities, and pref- rious risks and should not be used. erably while the infant is still being breastfed, to reduce the risk of developing of intolerance (celiac disease). No benefits of a generally low-aller- Feeding Solid Foods (Complementary Foods, gen diet in infancy have been documented, and Beikost) hence the exclusion or delayed introduction of complementary food products considered aller- From about the end of the first half of infancy, genic is not recommended. breast milk and infant formula on their own cannot adequately meet the nutrient requirement of a healthy baby. For their optimal development in- Beverages fants require additional nutrients, such as the trace elements iron and zinc. The introduction of When 3 meals per day of complementary feeding solid foods over time should gradually get the are given, children should be offered water. Prior child used to an increasing variety of foods and, to reaching 3 solid food meals per day, no liquid around the age of about 1 year, to family foods. in additional to breast milk or infant formula is The first complementary foods should not be giv- needed, except for situations with fever, vomit- en later than the age of 26 weeks but not before ing or diarrhea. Regular cow’s milk should be of- the age of 17 weeks. As the first solid food, a mix- fered as a drink only after the first year of life to ture of pulpy vegetables, potatoes and meat can avoid adverse effects, for example on iron ab- be recommended which provides iron and zinc sorption. with high bioavailability (fig. 1). In about month-

Feeding My Baby – Advice for Families 295 Koletzko B. (ed): Pediatric Nutrition in Practice. Basel, Karger, 2008, pp 296–297

4 Annex

4.5 Increasing Dietary Energy and Nutrient Supply Berthold Koletzko ؒ Katharina Dokoupil

Infants and children with growth faltering often erance. Concentrations of 1 17% (+30% energy need an enhanced intake of energy and nutrients. density) should usually be avoided. Increasing the energy density, i.e. the amount of Disadvantage: Increased formula density in- energy per food portion or per milliliter of a liq- creases renal solute load and may reduce toler- uid food, can increase the total energy intake ance. even when the total amount of food taken remains limited. Such an increase in energy density Addition of Glucose Polymers can be achieved by using one or several elements Glucose polymers (dextrin maltose or glucose of a stepwise approach. polymer mixtures) can be added with stepwise increasing concentrations from 1 up to 4 g/100 Elements of a stepwise approach to increase energy ml, which adds ; 3.9–15.6 kcal/100 ml milk/for- and nutrient supply mula. The concentration should be increased (1) Analysis of needs, diet and feeding situation stepwise according to individual tolerance. (2) Individual, professional counseling on dietary Disadvantage: The supply of essential nutri- choices and on feeding practice ents per kilocalorie is reduced and may not al- (3) Offer meals and snacks more frequently ways be sufficient, particularly for catch-up (4) Preferential choice of energy-dense foods, drinks and snacks growth. (5) Enrichment of formula and home foods with glucose polymers and/or oils Addition of Glucose Polymer – Fat Mixtures to (6) Use of drinkable supplements (sip feeds) Infant Formula (7) Tube feeding (nocturnal/continuous) (8) Parenteral nutrition Preparations of glucose polymers with either vegetable oil (e.g. soybean oil, rapeseed oil) or medium chain triglycerides (MCTs) from coconut oil can be added in stepwise increasing concen- Infants: Options for Increasing Energy Density trations from 1 to 4 g/100 ml, which adds ; 5.1– of Expressed Human Milk or Infant Formula 10.5 kcal/100 ml milk/formula. The concentration should be increased stepwise according to Increased Concentration of Infant Formula individual tolerance. The use of 15% powder instead of 13% increases Usually mixtures with vegetable oils provid- energy density by 15%. The concentration should ing long-chain fats should be used. Mixtures with be increased stepwise according to individual tol- MCTs are only indicated in cases of severe fat mal-assimilation (e.g. marked cholestasis). MCTs Children: Options for Increasing Energy may be quickly hydrolyzed when added to hu- Density of Foods man milk which can limit tolerance. Disadvantage: The supply of essential nutri- Addition of Fats and Oils to Foods ents per kilocalorie is reduced. Use of extra butter, margarine, vegetable oils, cream, fatty cheese, e.g. extra fat, cream and Addition of Oils or of Fat Emulsions cheese with vegetables, starchy foods, milk prod- Vegetable oils can be mixed with milk/formula ucts. Increase concentration stepwise according and provided at ;1 g/kg body weight per day; to individual tolerance. 9 kcal/g. Added oils tend to separate (oil droplets Disadvantage: The supply of essential nutri- on the surface) and, depending on the mode of ents per kilocalorie is reduced and may not al- feed delivery, may only be delivered in part to the ways be sufficient, particularly for catch-up recipient infant. growth. An enteral vegetable oil (long-chain triglyceride) in water emulsion providing 4.5 kcal/ml is Addition of Glucose Polymers to Drinks and available which can be mixed with milk/for- Semisolid Foods mula. Glucose polymers can be added in stepwise in- Disadvantage: The supply of essential nutri- creasing concentrations up to 5–10 g/100 g (19.5– ents per kilocalorie is reduced. 38 kcal/100 g) in pre-school children and up to 10–15 g/100 g (38–58.5 kcal/100 g) in school-age Use of Enteral Infant Feed children to drinks (e.g. milk, tea, juice) and semi- High-energy infant feeds ( ; 1 kcal/ml) with bal- solid foods (e.g. soups, pureed vegetables). In- anced nutrient composition are a good alterna- crease concentration stepwise according to indi- tive particularly for infants who need a high en- vidual tolerance. ergy and nutrient density over prolonged time Disadvantage: The supply of essential nutri- periods. ents per kilocalorie is reduced and may not always be sufficient, particularly for catch-up growth. Children: Preferential Choice of Energy-Dense Foods, Drinks and Snacks Use of Liquid Feeds with High Energy and Nutrient Density • Energy-dense foods, e.g. deep fried foods High-energy liquid feeds (sip feeds, ;1–1.5 kcal/ (French fries), fatty foods ml) with balanced nutrient composition are a • Energy-dense drinks, e.g. milk shakes, high- good alternative, particularly for children who fat milk/chocolate drinks. For many children need a high energy and nutrient density over pro- 4 it is easier to drink extra calories than to take longed time periods. them with more solid foods • Energy-dense snacks, e.g. ice-cream without or with extra whipped cream, chocolate, chocolate mousse or energy-dense puddings (with cream), potato chips (fried in oil), nuts, nuts with raisins

Increasing Dietary Energy and Nutrient Supply 297 Author Index

Bergmann, K.E. 125 Heine, R.G. 184 Salminen, S. 80 Bergmann, R.L. 125 Hermoso, M. 285 Saloojee, H. 162 Bhattacharjee, L. 133 Himes, R. 21 Shulman, R. 21 Bhutta, Z. 155 Hulst, J. 248 Solomons, N.W. 57, 137 Böhles, H. 208 Stallings, V.A. 17 Burdette, H. 17 Katz, R.M. 196 Steltzer, M. 229 Butte, N. 31 Kien, C.L. 42 Kolaček, S. 142 Tang, M. 80 Carricato, M. 219 Koletzko, B. 27, 67, 147, 214, Tolboom, J. 130 Cooper, P. 162 285, 293, 296 Tontisirin, K. 133 Koletzko, S. 106 Turck, D. 90 de Onis, M. 254 Dokoupil, K. 293, 296 Lentze, M.J. 76 Uauy, R. 47

Elango, R. 37 Malina, R.M. 62 Valdes-Ramos, R. 13 Marcos, A. 239 Valverde, M.A. 118 Fewtrell, M. 102 Mehta, T. 191 Van Goudoever, H. 248 Fisberg, M. 118 Mena, P. 47 Vitolo, M. 118 Fleischer Michaelsen, K. 1, 85 Moreno, L.A. 114 Fuchs, G.J. 52 Wabitsch, M. 151 Pencharz, P. 37 Were, F.N. 204 Gold, B. 191 Przyrembel, H. 71, 110 Wilschanski, M. 224 Goulet, O. 171 Puntis, J.W.L. 6, 244 Griffiths, A.M. 219 Yamashiro, Y. 122 Guandalini, S. 178 Reddy, V. 98 Guignard, J.-P. 234 Rees, L. 234 Zemel, B. 17 Rings, E. 168 Ziegler, E.E. 200, 271 Subject Index

Acidemia, organic 210 maternal allergen exclusion Basal metabolic rate, estimation Acute renal failure during pregnancy and 31, 32 definition 234 lactation 106, 107 Behavioral therapy, eating disorders dietary intervention protein sources in infant 242 purposes 234 feeding 108 Beverages, recommendations 295 specifications 234, 235 Amino acids Bioelectrical impedance analyzer, Adolescents infant and child requirements body composition evaluation 20 calcium requirements 116 37–40 Biological programming, long-term cystic fibrosis nutrition 225 intensive care unit requirements health 67–70 eating patterns 114, 115 249, 250 Birth weight, long-term health energy requirements 115 parenteral nutrition 149 effects 67, 68 growth and nutritional short bowel syndrome and Body mass index requirements 115 protracted diarrhea of CDC Growth Charts iron requirements 116 infancy enteral feeding boys 278 low income population formulas 174 girls 279 challenges 118–120 Anorexia nervosa Euro-Growth Charts protein requirements 115 alarm signs 240 boys 282 vitamin requirements 116 behavioral therapy 242 girls 283 zinc requirements 116 differential diagnosis 241 maternal measurement 125 AIDS, see Human malnutrition management 241, reference charts in growth 1, 4 immunodeficiency virus 242 World Health Organization Albumin, nutritional assessment nutrient intake patterns 241 Child Growth Standards 22, 25 pathophysiological features 239, boys 266 Allergy 240 girls 267 clinical manifestations of food physical examination 240 Bone marrow transplantation allergy 186, 187 Anthropometry 245 complementary food allergens growth charts, see Growth Bone mineral density 19 104 head circumference 8 Breastfeeding dietary management 188, 189 height 8 allergy avoidance 107 food allergens 184, 185 indices 11 benefits for infant and mother investigation 187, 188 length 8 85, 86, 90 pathophysiology 185, 186 mid-upper arm circumference environmental contaminants prevention 8 87, 88 breastfeeding 107 skinfold thickness 1, 4, 8, 9 hospitalized infants 88 complementary food timing weight 7, 8 human immunodeficiency virus 108 Arachidonic acid 48–50 transmission 86, 87, 162, 5 hydrolyzed infant formula 163, 165 107, 108 hypernatremic dehydration 87 Breastfeeding (continued) stature-for-age Congenital heart disease medication excretion 88 boys 276 growth considerations obesity risk reduction 69 girls 277 caloric intake optimization practical recommendations 293, weight-for-age 230–232 294 boys 274 consultations 232 preterm infants 206, 207 girls 275 enteral nutrition modes short bowel syndrome and Celiac disease 232 protracted diarrhea of associated diseases 180, 181 intervention timing 230 infancy 172, 173 clinical presentation medical management 230 support 88 atypical disease 180 non-cardiac etiology 233 Breast milk overview 179 types in growth delay 229, 230 components 85 typical disease 179 Constipation, prevention 45 cow’s milk comparison 86 diagnosis 181, 182 Contaminants lipids 50 epidemiology 178 breast milk 87, 88 Bulimia nervosa gluten avoidance foods 72 alarm signs 240 complementary foods 104 Coronary heart disease, birth behavioral therapy 242 pathophysiology 178, 179 weight effects 67, 68 differential diagnosis 241 prevention 181, 182 Crohn disease malnutrition management 241, treatment 181 enteral nutrition 242 Child Growth Standards, see World patient selection 220 pathophysiological features 239, Health Organization Child rationale 219 240 Growth Standards therapeutic regimens 220, physical examination 240 Cholestatic liver disease 221 Burn injury, see Intensive care dietary intake 168, 169 growth facilitation 221, 222 macronutrient requirements remission maintenance 221 Calcium 169 Cystic fibrosis adolescent requirements 116 micronutrient requirements 170 epidemiology 224 chronic renal failure Cholesterol, see malnourished child requirements 236, 237 Hypercholesterolemia management 226, 227 pregnancy requirements Chronic kidney disease malnutrition pathogenesis 226 128 definition 234 nutrition vegetarian diet and deficiency dietary intervention adolescents 225 risks 131 calcium 236, 237 assessment 225, 226 Cancer, see Malignant disease energy 235 children 225 Carbohydrate minerals 237 infants 225 assimilation by small intestine phosphate 236, 237 toddlers 225 and colon 43 potassium 236 pathophysiology 224 functional effects 44, 45 protein 235–237 indigestible carbohydrates purposes 234 Dextrin maltose fiber 44 vitamins 237 Diabetes mellitus metabolism 42 Citric acid cycle, defects 212, 213 type 1 oligosaccharides and Complementary foods celiac disease association prebiotics 44 allergy avoidance 104 180, 181 intensive care unit requirements definition 102 dietetic treatment 209 250 energy 103 epidemiology 208 malabsorption testing 26 gluten introduction 104 ketoacidosis management obesity role of intake 152 iron 103, 104 208, 209 CDC Growth Charts recommendations 295 type 2 body mass index-for-age salt and sugar content 104 birth weight effects in later boys 278 taste and food acceptance 104 life 67, 68 girls 279 timing 102, 103, 108 food glycemic index and length-for-age vegan diets 104 risks 44, 45 boys 274 zinc 104 Dialysis, see Chronic renal failure girls 275 Computed tomography, body Diarrhea overview 271, 272 composition evaluation 20 infectious agents 155, 156

300 Subject Index management Crohn disease etiology 196, 197 diet selection 158, 159 patient selection 220 evaluation 198 follow-up 159, 160 rationale 219 treatment 198, 199 initial resuscitation and therapeutic regimens 220, 221 Feeding history, nutritional stabilization 158 definition 142 assessment 6, 7 micronutrient delivery Fiber supplementation 159 initiation 145 colon cancer studies 45 oral rehydration solution 52, modes 145 constipation prevention 45 156, 158 routes 144 definition 44 zinc 157, 159 sites 144 Fluids and electrolytes pathogens and clinical formula environment and physical syndromes 157 composition 142, 143 activity effects 55 prevention 156 selection criteria 143, 144 gastrointestinal regulation 53 Docosahexaenoic acid indications 142, 143 ion flux regulation infant and child requirements intensive care 251 intercellular regulation 54 48–50 malignant disease 246, 247 intracellular regulation 53, 54 pregnancy requirements 128 preterm infants 202, 205–207 rehydration principles 55, 56 Doubly labeled water, total energy short bowel syndrome and short bowel syndrome and expenditure prediction 31, 32 protracted diarrhea of protracted diarrhea of Down syndrome, celiac disease infancy 172–176 infancy 175 association 181 Estimated average requirement 28 sodium balance regulation 53 Dual energy X-ray absorptiometry Euro-Growth Charts water balance regulation 53 body composition evaluation body mass index-for-age Folic acid, pregnancy requirements 19 boys 282 127 bone mineral density evaluation girls 283 Follow-on formula 19 curves 1, 2 composition 94, 95 length-for-age overview 91 Eating disorders, see Anorexia boys 280 Food allergy, see Allergy nervosa, Bulimia nervosa girls 281 Food culture, Japanese perspective behavioral therapy 242 overview 271, 272 dietary habit changes and health classification 240, 241 weight-for-age consequences 123, 124 differential diagnosis 241 boys 284 global food infiltration 122, 123 malnutrition management 241, girls 284 intervention 124 242 meal patterns 124 micronutrient deficiencies 139, Fat traditional food benefits 122 140 addition and energy density Food intolerance Energy increase 297 definition 184 complementary foods 103 breast milk lipids 50 lactose 187 parenteral nutrition 148, 149 child intake 50, 51 Food safety requirements fatty acid contaminants 72 adolescents 115 essentiality 48, 49 diseases 73, 74 chronic renal failure 235 trans fatty acids 50 infant formula 74 intensive care 249 types 47 overview 71 pregnancy 126 infant intake 48 recommendations 74 preterm infants 200, 201 intensive care unit requirements residues 72 Energy density 250 toxicology 72, 73 increasing options 297 lipoprotein and cholesterol Formula, see Enteral nutrition, obesity role 152 response in diet 217 Infant formula Energy expenditure, see Physical malabsorption testing 26 Fructooligosaccharides 44, 45 activity, Resting energy obesity role of intake 152 Fructose intolerance, hereditary 212 expenditure, Total energy parenteral nutrition lipids 149, expenditure 150 Galactosemia 212 Enteral nutrition Feeding disorders Gastroesophageal reflux disease 5 complications 145 definition 196 congenital heart disease congenital heart disease 232 epidemiology 196 association 230

Subject Index 301 Gastroesophageal reflux disease infant rules of thumb 10 infant feeding guidelines 163– (continued) patterns 10, 11 165 diagnosis 193, 194 nutritional problems 2, 3 micronutrient deficiencies 166 epidemiology 191, 192 organs 1, 3 Hypercholesterolemia pathophysiology 191 regulation 2 diagnosis 216 symptoms 192 World Health Organization dietary treatment 216, 217 treatment 194, 195 Child Growth Standards epidemiology 215, 216 Gastrointestinal tract body mass index-for-age etiology 216 development 76–79 boys 266 lipoprotein metabolism 214, 215 fluid and electrolyte regulation girls 267 Hypoalbuminuria 21, 25 53 head circumference-for-age Gluconeogenesis, defects 212 boys 268 Infant formula Glucose girls 269 allergy avoidance with parenteral nutrition 149 length/height-for-age hydrolyzed infant formula polymer addition and energy boys 260 107, 108 density increase 296, 297 girls 261 composition Glutamine, short bowel syndrome Multicentre Growth follow-on formula 94, 95 and protracted diarrhea of Reference Study 255, 256 liquid or powdered formulas infancy enteral feeding formulas overview 254–256 92, 93 174 weight-for-age long-chain polyunsaturated Gluten, complementary foods boys 258 acids 91, 95 104 girls 259 prebiotics 95, 96 Glycogen storage defect 1 212 weight-for-height recommendations 91 Growth boys 264 thickening agents 91 assessment 272 girls 265 follow-on formula 91 CDC Growth Charts weight-for-length food safety 74 body mass index-for-age boys 262 hypoallergenic formulas 188, boys 278 girls 263 189 girls 279 Gut microbiota marketing length-for-age first 6 months 81 education campaign 100 boys 274 immune development role 82 ethical marketing campaign girls 275 intestinal function 82, 83 100 overview 271, 272 maintenance and modulation 83 International Code of stature-for-age 6 months to 2 years 81 Marketing of Breast-Milk boys 276 sources in neonates 80 Substitutes girls 277 succession 80, 81 article extracts 99 weight-for-age monitoring 99–100 boys 274 Hazard Analysis and Critical origins 98 girls 275 Control Point 71, 74 violations 99 curves 1, 2 Head circumference preparation, storage and Euro-Growth Charts anthropometry 8 handling 91 body mass index-for-age World Health Organization recommendations 294, 295 boys 282 Child Growth Standards soy protein formula indications girls 283 boys 268 96 length-for-age girls 269 Inflammatory bowel disease, see boys 280 Heart disease, see Congenital heart Crohn disease girls 281 disease, Coronary heart disease Intensive care overview 271, 272 Human immunodeficiency virus energy expenditure in trauma weight-for-age breastfeeding transmission risks and burn injury 248 boys 284 and prevention 86, 87, 162, malnutrition prevalence in girls 284 163, 165 pediatric intensive care unit long-term health relationships 3 child feeding guidelines 165, 248 monitoring 3, 4 166 nutritional requirements nutritional assessment highly active antiretroviral amino acids 249, 250 charts 10 therapy in children 166 carbohydrate 250

302 Subject Index energy 249 Magnetic resonance imaging, body United States and Canada fat 250 composition evaluation 20 reference values 290 trauma and burn injury 250 Malignant disease WHO/FAO/UNU reference nutritional support bone marrow transplantation 245 values 291, 292 compliance 251, 252 enteral nutrition 246, 247 Nutritional assessment, see follow-up 252, 253 late nutritional complications Malnutrition formulas 251 247 anthropometry 7–9 goals 250 malnutrition body composition evaluation route 251 mechanisms 244, 245 19, 20 timing 251 risk factors 244, 245 dietary intake assessment 15, International Code of Marketing of nutritional support provision 16 Breast-Milk Substitutes 245, 246 dual energy X-ray article extracts 99 parenteral nutrition 246, 247 absorptiometry 17, 19 monitoring 99–100 Malnutrition feeding history 6, 7 origins 98 classifications 11 growth violations 99 definitions 11 charts 10 Inulin 44, 45 intervention guidelines 11, 12 infant rules of thumb 10 Iodine Maple syrup urine disease 210 patterns 10, 11 deficiency consequences 139 Maximal residue levels 72 history 13, 14 pregnancy requirements 127 Medium-chain acyl-CoA intake evaluation 6, 7 Ion channels, regulation 54 dehydrogenase deficiency 211, laboratory tests Iron 212 malabsorption testing 26 adolescent requirements 116 Metabolic programming, long-term overview 21–24 complementary foods 103, 104 health 67–70 serum proteins 21, 25 deficiency Microbiota, see Gut microbiota tests and reference levels consequences 138 Micronutrient deficiency, see also 22–24 risk factors 138 specific micronutrients vitamins and minerals 25, pathogenic organism needs 138, chronic diseases 140 26 139 eating disorders 139, 140 resting energy expenditure pregnancy requirements 128 human immunodeficiency virus estimation 17–19 vegetarian diet and deficiency 166 risks 131 iatrogenic causes 140, 141 Obesity mechanisms and contexts 137, breastfeeding in risk reduction Lactation 138 69 allergen exclusion 106, 107 Milk, see Breast milk, Infant energy expenditure effects 65, recommended dietary formula 66 allowances Minerals, see also specific minerals; etiology calcium 128 see Trace elements carbohydrate intake 152 docosahexaenoic acid 128 Multicentre Growth Reference energy density of diet 152 folic acid 127 Study 255, 256 family factors 153 iodine 127 fast food 153 iron 128 Necrotizing enterocolitis 200 fat intake 152 vitamin A 127 No observed adverse effect levels portion size 152 vitamin B6 128 72, 73 school environment 154 vitamin B12 128 Nutrient intake values growth effects 3 vitamin D 128 Australia and New Zealand treatment 151–153 zinc 128 reference values 285, 286 trends 151 Lactose intolerance 187 definitions 28 OptimiX Leukemia, see Malignant disease German, Austrian and Swiss diet composition 112 Linoleic acid 48, 49 reference values 287 food choices 112, 113 ␣-Linolenic acid 48, 49 limitations in estimation 28–30 meal patterns 112 Lipids, see Fat Nordic reference values 288 principles of child diets and Lipoproteins, metabolism 214, 215 overview 27, 28 eating 110, 111 5 Low birthweight infants, see United Kingdom reference Oral rehydration solution 52, 55, Preterm infants values 289 156, 158

Subject Index 303 Parenteral nutrition riboflavin 128 Reference nutrient intakes, see indications 147 vitamin A 127 Nutrient intake values intensive care 251 vitamin B6 128 Rehydration, principles 55, 56 malignant disease 246, 247 vitamin B12 128 Renal failure, see Acute renal prescription 150 vitamin D 128 failure, Chronic renal failure preterm infants 201, 202 zinc 128 Resting energy expenditure, recommendations by age 147, 148 undernutrition 134 estimation 17–19 requirements weight loss after delivery 125 Riboflavin amino acids 149 Preterm infants deficiency consequences 139 energy 148, 149 early nutrition pregnancy requirements 128 glucose 149 enteral nutrition 202, lipids 149, 150 205–207 Safety, see Food safety water 148 parenteral nutrition 201, 202 Short bowel syndrome Pediatric intensive care unit, see late nutrition 202, 203 diet Intensive care micronutrient requirements breast milk 172, 173 Phenylketonuria 205, 207 enteral formula 172–176 epidemiology 209 milk volume requirements by enteral feeding rationale 172 maternal management 210 birthweight 205 overview 171, 172 treatment 209, 210 protein and energy Skinfold thickness Phosphate, chronic renal failure requirements 200, 201 nutritional assessment 8, 9 requirements 236, 237 Protein reference charts in growth 1, 4 Physical activity, see Total energy adolescent requirements 115 Small intestine bacterial expenditure amino acid requirements 37–40 overgrowth 174 benefits 64, 65 chronic renal failure Sodium fluid and electrolyte effects 55 requirements 235–237 balance regulation 53 measurement 62, 63 malabsorption testing 26 cotransporters 53, 54 obesity effects 65, 66 pregnancy requirements 126 retention 52 physical fitness comparison 62 preterm infant requirements Soy protein formula, indications pregnancy 126, 127 200, 201 96 recommendations 35, 36, 64 quality 39 undernutrition effects 65 requirements Thermal effect of feeding 31, 32 variation with sex and age 63, 64 children and adolescents 38 Toddlers Population reference intake 28 definition 37 cystic fibrosis nutrition 225 Portion size, obesity role 152 expression 38 diet composition 112 Potassium, chronic renal failure infants 38 food choices 112, 113 requirements 236 serum proteins and nutritional meal patterns 112 Prebiotics assessment 21, 25 principles of diets and eating functional effects 44, 45 sources 41 110, 111 infant formula 95, 96 Proton pump inhibitor, Tolerable daily intake 73 Pregnancy gastroesophageal reflux disease Total body electrical conductivity, allergen exclusion 106, 107 diagnosis and management 193, body composition evaluation 20 energy requirements 126 195 Total energy expenditure gestational weight gain 125, 126 Protracted diarrhea of infancy components 31, 32 micronutrient deficiency diet estimation screening 128 breast milk 172, 173 children and adolescents 34, phenylketonuria 210 enteral formula 172–176 35 physical activity 126, 127 enteral feeding rationale 172 doubly labeled water 31, 32 protein requirements 126 overview 171 infants 32–34 recommended dietary Pyruvate dehydrogenase, defects physical activity allowances 212, 213 recommendations 35, 36 calcium 128 Trace elements docosahexaenoic acid 128 Recommended dietary allowance, caveats and precautions 60, 61 folic acid 127 see also specific nutrients intrinsic sources 57, 58 iodine 127 definition 28 laboratory tests for deficiency iron 128 pregnancy, see Pregnancy 25, 26

304 Subject Index supplementation 59, 60 Vitamin B12 head circumference-for-age supplemented sources 58, 59 deficiency consequences 139 boys 268 Trans fatty acids 50 pregnancy requirements 128 girls 269 Trauma, see Intensive care vegetarian diet and deficiency length/height-for-age risks 131 boys 260 Undernutrition Vitamin D girls 261 definition 133 pregnancy requirements 128 Multicentre Growth Reference family and community vegetarian diet and deficiency Study 255, 256 orientation services 135, risks 131 overview 254–256 136 Vitamins, see also specific vitamins weight-for-age infant and young child feeding adolescent requirements 116 boys 258 134, 135 caveats and precautions 60, 61 girls 259 maternal 134 chronic renal failure weight-for-height primary undernutrition 134 requirements 237 boys 264 Upper nutrient level 28 intrinsic sources 57, 58 girls 265 Urea cycle, defects 211 laboratory tests for deficiency weight-for-length 25, 26 boys 262 Vegetarian diet supplementation 59, 60 girls 263 complementary foods 104 supplemented sources 58, 59 nutrient deficiency risks 131, Zinc 132 Water, balance regulation 52, 53 adolescent requirements 116 overview 130, 131 World Health Organization Child complementary foods 104 Vitamin A Growth Standards deficiency consequences 139 deficiency consequences 139 body mass index-for-age diarrhea management 157, 159 pregnancy requirements 127 boys 266 pregnancy requirements 128 Vitamin B6, pregnancy girls 267 vegetarian diet and deficiency requirements 128 risks 131

Subject Index 305