Placental Function and Fetal Nutrition

Nestle" Nutrition Workshop Series Volume 39

PLACENTAL FUNCTION AND FETAL NUTRITION

EDITED BY FREDERICK C BATTAGLIA

NESTLE NUTRITION SERVICES

Liooincott - Raven

PLACENTAL FUNCTION AND FETAL NUTRITION The 39th Nestle Nutrition Workshop, Placental Function and Fetal Nutrition, was held in Ashdown Park, Sussex, England, in the spring of 1996.

Behind: M. Kohler, D. Briggs, A. Staudach, T. Schwenzer, E. Friedrich, K. Nicolaides, P. Finne, P. Soothill, M. Maganaris, N. Lashneva (+ in front), C. Costalos, K. Page (+ in front), N.M. Shilina, A. Fournie, J. Dobbing, P. Aggett, J. Girard, J. Milliez, D. Candy, M. Mikati, U. Preysch, S.K. Nassar, C. Sibley, H. Schneider, T. Chard, K. Godfrey, A. Jensen, A.A. Pourvaghar, G. Csakany, M.S.W. Lum, A.A. Yahava, G.S.H. Yeo, A. Varvarigou, R. Claydon. 1st Row: S. Devane, Qi Pei Liu, Y. Ma, A. Shen, G. Dimaano, Z. Wang, S. Liu, P. Lumbiganon, M. El-Essa, J. Gadzinowski, L. Grahnquist, H.Z. Abidin, S. Nalliah, P. Steenhout, B. Hadibroto, Z.T. Tjaniago, K. Taher, L. Cedard, C. Williams, P. Duc-Goiran, A. Marini, G. Meschia, N. Mumjiev, S. Achanna, S. Sethavanich. Seated: E. Herrera, H. Valensise, E.S. Ogata, M.J. Soares, R.V. Anthony, D.M. Campbell, M.T. Clandinin, J.A. Owens, F. Haschke, R.D.H. Boyd, F.C. Battaglia, A.M. Marconi, F. Talamantes, M.J. Rennie, G. Pardi, R. Huch. Nestle Nutrition Workshop Series Volume 39

PLACENTAL FUNCTION AND FETAL NUTRITION

Editor

Frederick C. Battaglia University of Colorado Health Sciences Center Department of Pediatrics Denver, Colorado, U.S.A.

NESTLE NUTRITION SERVICES

Nestle

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Library of Congress Cataloging-in-Publication Data Placental function and fetal nutrition / editor, Frederick C. Battaglia; Nestle Nutrition Services. p. cm.—(Nestle Nutrition workshop series ; v. 39) "39th Nestle Nutrition Workshop which was held at Ashdown Park Hotel in East Sussex, England in the spring of 1996"—Pref. Includes bibliographical references and index. ISBN 0-7817-1406-0 1. Fetus—Nutrition—Congresses. 2. Placenta—Physiology—Congresses. 3. Maternal-fetal exchange—Congresses. I. Battaglia, Frederick C, 1932- . II. Nestle Nutrition Services. III. Nestle Nutrition Workshop (39th : 1996 : East Sussex, England) IV. Series. [DNLM: 1. Placenta—physiology—congresses. 2. Fetus—embryology—congresses. 3. Nutrition—in pregnancy—congresses. 4. Fetal Transport—physiology—congresses. Wl NE228 v.39 1997 / WQ 212 P698 1997] RG615.P53 1997 612.6'3—dc21 DNLM/DLC for Library of Congress

Care has been taken to confirm the accuracy of the information presented and to describe generally accepted practices. However, the authors, editors, and publisher are not responsible for errors or omissions or for any consequences from application of the information in this book and make no warranty, express or implied, with respect to the contents of the publication. The authors, editors, and publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accordance 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 or infrequently employed drug. Some drugs and medical devices presented in this publication have Food and Drug Administration (FDA) clearance for limited use in restricted research settings. It is the responsibility of the health care provider to ascertain the FDA status of each drug or device planned for use in their clinical practice. Preface

This book is the result of the 39th Nestle Nutrition Workshop which was held at Ashdown Park Hotel in East Sussex, United Kingdom, in the spring of 1996. Interna- tional experts in placental function and fetal nutrition were invited to discuss their work. The experts included basic scientists and clinical scientists. Ashdown Park provided a magnificent setting for a conference, one which encouraged informal discussion apart from the formal program. The topic of placental function and fetal nutrition is an extremely important and timely one. The development and growth of a child is determined to a great extent by its in utero development. Fetal growth restriction, or intrauterine growth retardation, is a striking example of clinical pathology associated with placental dysfunction and fetal malnutrition. It is now clear that such effects can have long-term implications. The timeliness of this Workshop comes from the availability of new imaging and research techniques, which permit studies in human pregnancy as well as in basic research. The conference had five sessions, in each of which a mixture of basic and clinical research topics was presented. This format led to lively exchange and discussion among basic scientists and clinicians. It was quickly apparent that a great deal of progress had been made towards understanding placental transport and metabolism and that some of the concepts which have emerged from basic research are now addressable in human pregnancies. While many questions remain unanswered, it was clear that a far more precise description of normal fetal growth and metabolism is emerging, with the possibility of exploring how specific maternal diseases affect fetal and placental nutrition. Within the lively discussion that followed all presentations, there were suggestions with potential therapeutic application to human pregnancies.

FREDERICK C. BATTAGLIA, M.D. Division of Perinatal Medicine Department of Pediatrics University of Colorado School of Medicine Denver, Colorado, U.S.A.

Foreword

The placenta plays a central role in the nutrition of the fetus. It provides nutrients and removes waste products. Placental size and structure, developmental and patho- logical processes, as well as metabolic interactions with the fetus, cooperate with placental transport and metabolic mechanisms to affect placental-fetal nutrient exchange both quantitatively and qualitatively. It is generally accepted that small placental size is the major determinant of intrauterine growth retardation (IUGR) in infants. Even though placental glucose transfer appears to be unchanged in IUGR it remains unclear whether the efficiency of placental amino acids transport is altered. Lipid transport, placental hormone production, polypeptide growth factors, and sig- nals originating from the fetus can also limit fetal growth. The 39th Nestle Nutrition Workshop, held in Ashdown Park, Sussex, United Kingdom and chaired by Professor F. Battaglia, allowed an interactive discussion between basic and clinically applied research in this field. It provided an opportunity not only to digest the progress made in our understanding of placental function and fetal nutrition, but also to outline the important questions for the future; among them, the prevention of IUGR and the nutritional requirements of the newborn with IUGR.

PROFESSOR F. HASCHKE, M.D. Vice-President Nestec Ltd. Vevey, Switzerland

Contents

Techniques for the Study of Placental Transport—Transfer of Chloride as an Example 1 R.D.H. Boyd, I.M. Doughty, J. Glazier, S. Greenwood, and C.P. Sibley

Placental Delivery of Amino Acids. Utilization and Production vs. Transport 21 Giacomo Meschia

Molecular Mechanisms of Placental Development 31 Michael J. Soares

Fetal Liver and the Placenta: An Interactive System 47 Frederick C. Battaglia

The Endocrine Function of the Placenta: Interactions Between Trophic Peptides and Hormones 59 Lise Cedard

The Endocrine Function of the Placenta: Human Placental Growth Hormone Variant 75 Frank Talamantes

Development of Hormone Receptors Within the Fetus 85 Russell V. Anthony, M.D. Fanning, and L.C. Richter

Regulation of Gene Expression by Nutrients During the Perinatal Period 103 Jean Girard, S. Hauguel-de Mouzon, F. Chatelain, P. Boileau, S. Thumelin, and J-P Pegorier

Oxygenation In Utero: Placental Determinants and Fetal Requirements 123 Julie A. Owens, K.L. Kind, and J.S. Robinson ix CONTENTS

Placental Transport in Fetal Growth Retardation 143 Edward S. Ogata, R.H. Lane, R.A. Simmons, and G.J. Reid

Fetal Lipid Requirements: Implications in Fetal Growth Retardation 157 Jacqueline Jumpsen, J. Van Aerde, and M. Thomas Clandinin

Maternal Lipid Metabolism and Its Implications for Fetal Growth . . 169 Emilio Herrera and M.A. Munilla

Oxygen Consumption and Protein Metabolism in the Human Fetus 183 Michael J. Rennie

Nutrient Supply in Human Fetal Growth Retardation 191 Anna Maria Marconi

Maternal Vascular Disease and Fetal Growth 199 Carlo Romanini and H. Valensise

Fetal Growth and Long-Term Consequences in Animal Models of Growth Retardation 215 Kathleen Holemans, L. Aerts and F.A. Van Assche

Drug Abuse 231 Doris M. Campbell

Effects of Maternal Smoking on Placental Structure and Function . . 247 K.R. Page, P. Bush D.R. Abramovich, P.J. Aggett, M.D. Burke, and T.M. Mayhew

Concluding Remarks 251

Subject Index 253 Contributors

Speakers

Russell V. Anthony M.Thomas Clandinin Animal Reproduction and Biotechnology Department of Agricultural, Food & Laboratory Nutritional Science and Department of Physiology Department of Medicine Colorado State University University of Alberta Fort Collins, Colorado 80523-1683, 4-10 Agriculture/Forestry Centre U.S.A. Edmonton, Alberta T6G 2P5, Canada Jean Girard Centre de Recherche sur VEndocrinologie Federick C. Battaglia Moleculaire et le Developpement Department of Pediatrics Centre National de la Recherche University of Colorado Health Scientifique Sciences Center 9 Rue Jules Hetzel 4200 E. Ninth Avenue, B-199 92190 Meudon, France Denver, Colorado 80262, U.S.A. Emilio Herrera Universidad San Pablo-CEU R.D.H. Boyd Urbanizacion Monteprincipe St. George's Hospital Medical School Ctra. Boadilla del Monte, km 5,300 Cranmer Terrace E-28668 Madrid, Spain London SW17 ORE, United Kingdom Anna Maria Marconi Department of Obstetrics & Gynaecology University of Milan-IBMS San Paolo Doris M. Campbell Via Antonio di Rudini 8 Department of Obstetrics & Gynaecology 20144 Milan, Italy University of Aberdeen Aberdeen Maternity Hospital Foresterhill Giacomo Meschia Department of Physiology Aberdeen AB9 2ZD, United Kingdom University of Colorado School of Medicine 4200 E. Ninth Avenue C240 Lise Cedard Denver, Colorado 80262, U.S.A. 1NSERM U 361 Matemite Baudelocque Edward S. Ogata Reprod. et Physiopathologie Obstetricale The Children's Memorial Hospital 123 Bid de Port-Royal 2300 Children's Plaza, #45 75014 Paris, France Chicago, Illinois 60614, U.S.A.

XI Xll CONTRIBUTORS

Julie A. Owens Alfred Staudach Department of Physiology Landeskrankenanstalten University of Adelaide Frauenklinik Adelaide, South Australia, 5005, Australia Mullner Hauptstra&e 48 A-5020 Salzburg, Austria

Michael J. Rennie Department of Anatomy & Physiology Session Chairmen University of Dundee Dundee DD1 4HN, United Kingdom Frederick C. Battaglia / Denver, USA Stuart Campbell / London, United Kingdom Carlo Romanini Tim Chard / London, United Kingdom Department of Obstetrics & Gynaecology Universita di Roma-Tor Vergata Kypros Nicolaides / London, United Piazza dell'Umanesimo 10 Kingdom 1-00144 Roma, Italy Peter Soothill / Brafo/, United Kingdom

Michael J. Soares Invited Attendees Department of Physiology University of Kansas Medical Center Siva Achanna / Malaysia 3901 Rainbow Blvd. Peter J. Aggett / United Kingdom Kansas City, Kansas 66160, U.S.A. Stuart Campbell / United Kingdom David C.A. Candy / United Kingdom Tim Chard / United Kingdom Frank Talamantes Christos Costalos / Greece Department of Biology University of California G.M. Csakany / Hungary Sinsheimer Laboratories Sean Devane / United Kingdom Santa Cruz, California 95064, U.S.A. John Dobbing / United Kingdom P. Duc-Goiran / France Mazen El-Essa / Kuwait F.A. Van Assche Per Finne / Norway Department of Obstetrics and Gynecology Alain Fournie / France Uz Gasthuisberg Ernst Friedrich / Germany Herestraat 49 B-3000 Leuven, Belgium Janusz Gadzinowski / Poland Keith Godfrey / United Kingdom Lena Grahnquist / Sweden Speakers Budi R. Hadibroto / Indonesia (no manuscript provided) Renate Huch / Switzerland Arne Jensen / Germany Abu Taher Khan / Bangladesh Giorgio Pardi Nina V. Lashneva / Russia Department of Obstetrics & Gynaecology University of Milan-IBMS San Paolo Qi Pei Liu I P.R. China Via Antonia di Rudini 8 Shunyun Liu I P.R. China 20144 Milan, Italy Milton Stew Wah Lum / Malaysia CONTRIBUTORS xiu

Pisake Lumbiganon / Thailand Christine Williams / United Kingdom Yanyan Ma/P.R. China Abd. Aziz Yahava / Malaysia Antonio Marini / Italy Hakimi Zainal Abidin / Malaysia Mohamad Mikati / Lebanon Jacques Milliez / France Nestle Representatives Nikola Mumjiev / Bulgaria S. Nalliah / West Malaysia Denise Briggs / Croydon, United Salah Kamel Nassar / Egypt Kingdom Kypros Nicolaides / United Kingdom Ralph Claydon / Croydon, United K.R. Page / United Kingdom Kingdom A-A Pourvaghar / Iran Gemma Dimaano / Manila, Tom Sanders / United Kingdom Philippines Henning Schneider / Switzerland Bianca-Maria Exl/Munich, Germany Thomas Schwenzer / Germany Ferdinand Haschke / Vevey, Soisaang Sethavanich / Thailand Switzerland Natalia M. Shilina / Russia Manfred Kohler / Munich, Germany Colin Sibley / United Kingdom Michalis Maganaris / Athens, Greece Peter Soothill / United Kingdom Ulrich Preysch / Vevey, Switzerland G.S.H. Yeo / Singapore Anna Shen / Beijing, P.R. China Z.T. Tjaniago / Indonesia Philippe Steenhout / Vevey, Herbert Valensise / Italy Switzerland Anastasia Varvarigou-Frima / Greece Pat Wright / Croydon, United Zhi-qiong Wang / P.R. China Kingdom

Nestle Nutrition Workshop Series

Volume 39: Placental Function and Fetal Nutrition Frederick C. Battaglia, Editor; 288 pp., 1997. Volume 38: Diarrheal Disease Michael Gracey and John A. Walker-Smith, Editors; 368 pp., 1997. Volume 37: Feeding from Toddlers to Adolescence Angel Ballabriga, Editor; 320 pp., 1996. Volume 36: Long-Term Consequences of Early Feeding John Boulton, Zvi Laron, and Jean Rey, Editors; 256 pp., 1996. Volume 35: Diabetes Richard M. Cowett, Editor; 320 pp., 1995. Volume 34: Intestinal Immunology and Food Allergy Alain L. de Week and Hugh A. Sampson, Editors; 320 pp., 1995. Volume 33: Protein Metabolism During Infancy Niels C. R. Raiha, Editor; 264 p., 1994. Volume 32: Nutrition of the Low Birthweight Infant Bernard L. Salle and Paul R. Swyer, Editors; 240 pp., 1993. Volume 31: Birth Risks J. David Baum, Editor; 256 pp., 1993. Volume 30: Nutritional Anemias Samuel J. Fomon and Stanley Zlotkin, Editors; 232 pp., 1992. Volume 29: Nutrition of the Elderly Hamish N. Munro and Giinter Schlierf, Editors; 248 pp., 1992. Volume 28: Polyunsaturated Fatty Acids in Human Nutrition Umberto Bracco and Richard J. Deckelbaum, Editors; 256 pp., 1992. Volume 27: For a Better Nutrition in the 21st Century Peter Leathwood, Marc Horisberger, and W. Philip T. James, Editors; 272 pp., 1993. Volume 26: Perinatology Erich Saling, Editor, 208 pp., 1992. Volume 25: Sugars in Nutrition Michael Gracey, Norman Kretchmer, and Ettore Ross, Editors; 304 pp., 1991. Volume 24: Inborn Errors of Metabolism Jilrgen Schaub, Frangois Van Hoof, and Henri L. Vis, Editors; 320 pp., 1991. Volume 23: Trace Elements in Nutrition of Children—II Ranjit Kumar Chandra, Editor, 248 pp., 1991. xvi Nestle Nutrition Workshop Series

Volume 22: History of Pediatrics 1850-1950 Buford L. Nichols, Jr., Angel Ballabriga, and Norman Kretchmer, Editors; 320 pp., 1991. Volume 21: Rickets Francis H. Glorieux, Editor; 304 pp., 1991.