The growth and development of children with prepubertal and pubertal eating disorders Cross sectional and longitudinal findings and their interpretation Dasha Elizabeth Nicholls Submitted for the degree of Doctor of Medicine Institute of Child Health University College London December 2001 f ProQuest Number: U 165741 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a complete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. uest. ProQuest U 165741 Published by ProQuest LLC(2016). Copyright of the Dissertation is held by the Author. All rights reserved. This work is protected against unauthorized copying under Title 17, United States Code. Microform Edition © ProQuest LLC. ProQuest LLC 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, Ml 48106-1346 Abstract Eating disorders are characterised by grossly disordered or chaotic eating behaviour. Nutritional compromise varies from extreme selectivity to severe malnourishment. During childhood, growth and development can be affected, some studies suggest permanently. Previously patient numbers have been limited, poor reference data used or growth parameters have not been taken into account when drawing conclusions about physical outcome for eating disorders in prepubertal and pubertal children. We studied consecutive cases referred to a specialist eating disorders service for children aged 7 to 16 years. Cross sectional (n=206) and longitudinal (n=126) data included anthropometry, body composition, bone density, and onset or resumption of menses. Findings were compared to normal children through a database designed to calculate age and gender matched scores from reference tables. The findings can be described in four categories. Firstly, in children who were malnourished, stature was significantly lower than age matched norms. Short stature was largely due to reduced spine length, and when adjusted for bone age was no longer evident, suggesting growth delay rather than stunting. Longitudinal data confirmed that ED subjects grew normally when adjusted for developmental stage, and those who had completed growth had a mean height on the 50^ centile. Secondly, principal components analysis for anthropometry showed a specific deficit in fat mass in malnourished subjects, although an equivalent relative loss of lean mass was seen when growth parameters are taken into account. Thirdly, methods for adjusting bone density measurements for bone size were compared. Calculating volumetric bone density allows the impact of malnutrition to be evaluated. Finally, pre and postmenarcheal ED subjects were compared with control girls in terms of onset or resumption of menses. Both groups menstruated at weights normally distributed around 0 BMI SDS, but BMI at menses was age dependent. 2 Acknowledgements There are many people to thank for help with this thesis. Among them are: Mike Preece for taking me on and keeping me going Bryan Lask for facilitating and inspiring Richard Stanhope for convincing me of the importance of this work Tam Fry and the Child Growth Foundation for financial support Tim Cole for his clarity of thought and statistical knowledge David Skuse for enabling me to continue what I started John Douglas for his patience and computing skill Sarah King and Alison Gaunt for their helpfulness in all things clinical and anthropometric Rachel Bryant-Waugh and the ED Team for their expertise and inspiration Isky Gordon and Rose de Bruyn for their radiological skill and support Gill G rim wood for her administrative help My students, Rachel Chater, Maria Lackberg, Sarah Walker, Hannah Mollitor and Marie Soderholm for their help with data collection Jonathon Wells for sharing his ideas Sandy Mather and Nicky Keay for sharing the journey All the children and young people, and their parents, for giving so much of their time and personal information Polly, Deborah and Jane for keeping me sane And my husband Russell for not keeping his promise Contents 1. Growth And Development in Early Onset Eating Disorders: a review of the literature .....................................................................................................................................20 1.1. introduction................................................................................................................20 1.2. Eating disorders in children and adolescents ....................................................... 21 1.2.1. Core concepts .................................................................................................. 21 1.2.2. Specific diagnostic issues in children and young adolescents.................. 31 1.2.3. Summary.............................................................................................................34 1.3. Overview of physical complications in early onset eating disorders ................ 34 1.4. Growth at puberty in normal adolescents .............................................................. 35 1.4.1. Determinants of growth .....................................................................................35 1.4.2. Puberty and its relationship to growth............................................................ 37 1.4.3. Changes in weight during adolescence .........................................................39 1.5. Pubertal delay and growth failure ........................................................................... 40 1.5.1. Bone age .............................................................................................................43 1.5.2. Impact of delayed puberty on adult height .....................................................44 1.6. Critical periods and nutritional programming.........................................................45 1.6.1. Adolescence as a critical period for growth .................................................. 45 1.6.2. Catch up growth.................................................................................................47 1.7. Growth in AN .............................................................................................................. 49 1.7.1. Short stature and A N ........................................................................................49 1.7.2. Growth retardation and catch-up growth ........................................................ 51 1.7.3. Summary............................................................................................................. 54 1.8. Nutritional status and menstruation.........................................................................55 1.8.1. The Frisch hypothesis....................................................................................... 56 1.8.2. Resumption of menses following A N ..............................................................58 1.8.3. Summary............................................................................................................. 59 4 1.9. Bone density ............................................................................................................59 1.9.1. Definitions of osteopenia and osteoporosis.................................................59 1.9.2. How is bone density measured? ....................................................................60 1.9.3. Interpreting bone density measurements in childhood ............................61 1.9.4. Bone accretion in childhood and adolescence ..........................................65 1.9.5. Influences on bone accretion and loss .......................................................... 66 1.10. Bone density in A N ............................................................................................68 1.10.1. Bone density in adult women and adolescents ....................................... 68 1.10.2. Reversibility of bone loss.............................................................................70 1.10.3. Summary................................................................................. 71 1.11. Conclusions........................................................................................................ 72 2. The measurement of body composition in children and adolescents with eating disorders................................................................................................................................... 73 2.1. Measuring body composition - why?...................................................................73 2.1.1. Level 1 : Estimates of body size .....................................................................75 2.1.2. Level 2: A ‘gold standard’ for body composition........................................ 76 2.1.3. Level 3: Defining abnormality ........................................................................ 77 2.2. Measuring body composition - how?...................................................................78 2.2.1. Anthropometry .................................................................................................78 2.2.1.1. Weight for height ........................................................................... 78 2.2.1.2. Body mass index (BMI)......................................................................82 2.2.1.3. Fat mass index (FMI) and fat free mass index (FFMI) ........................84 2.2.1.4. Skinfold thickness.....................................................................................