Children With Idiopathic Short Stature Are Poor Eaters and Have Decreased Body Mass Index Stefan A. Wudy*; Sandra Hagemann, MD*; Astrid Dempfle, PhD‡; Gundula Ringler, MSC‡; Werner F. Blum*§; Lars D. Berthold, MD࿣; Gerhard Alzen࿣; Ludwig Gortner¶; and Johannes Hebebrand# ABSTRACT. Objective. In children with idiopathic s.org/cgi/doi/10.1542/peds.2004-1684; eating behavior, short stature (ISS), studies investigating body mass index short stature, body mass index, leptin, ghrelin. (BMI) or parameters of satiety regulation are scarce, and studies analyzing eating behavior are lacking. Methods. We recruited 214 children (123 index cases ABBREVIATIONS. CDGP, constitutional delay of growth and and 91 siblings) with ISS from 123 families. Affected puberty; FSS, familial short stature; ISS, idiopathic short stature; IGF-I, insulin-like growth factor I; IGFBP-3, insulin-like growth children had to have a body height <5th percentile, or, in factor–binding protein 3; CEBQ, Child Eating Behavior Question- the case of siblings, the body height of 1 child had to be naire; SDS, standard deviation score; LFFQ, Leeds Food Fre- <5th percentile and the other <15th percentile. Medical quency Questionnaire. histories were recorded by using structured and stan- dardized interviews. Eating behavior was assessed by using the Child Eating Behavior Questionnaire. Percent hort stature is the most common cause for re- energy intake as fat was assessed by using the Leeds ferrals to pediatric endocrinologists. Many of Food Frequency Questionnaire. Endocrine markers of these patients have no identifiable medical ab- body weight regulation (leptin, ghrelin) were determined S normality and are classified with diagnoses such as in serum. constitutional delay of growth and puberty (CDGP), Results. Compared with population norms, BMI was -؊ familial short stature (FSS), or idiopathic short stat significantly lower (mean: 0.33 standard deviation ure (ISS). For most of these patients, the etiology of score). Furthermore, there was decreased food respon- siveness (mean Child Eating Behavior Questionnaire their short stature is currently unknown, although it score: 1.9; population mean: 2.4), reduced enjoyment of is believed that genetic variations are the underlying food (3.2 vs 3.9), emotional undereating (2.6 vs 3.0), lower cause.1,2 In young children, CDGP is typically de- desire to drink (2.0 vs 2.8), and increased fussiness over fined by short stature (height below the third age- food (3.2 vs 2.9). When the sample was subdivided into and gender-specific percentile), bone-age retardation the 2 groups of “good” and “poor” eaters according to the of at least 1 year, and a positive family history of mothers’ assessment of the current eating behavior, re- delayed growth and pubertal development; how- duction in BMI as well as the behavioral characteristics ever, in a strict sense, the diagnosis cannot be made already delineated in the total sample were found to be before the time of puberty, when a delay in sexual even more consistent in the subgroup of poor eaters. In maturation becomes evident. Patients with FSS re- the total sample of our children, as well as in both sub- groups, serum leptin (adjusted for gender, BMI, and Tan- veal a family history of short stature, whereas osse- ner stage) was found to be moderately raised but did not ous development and sexual maturation are appro- differ between poor and good eaters. Total serum ghrelin priate for chronological age. In case both bone age was not different between poor and good eaters. and parental height are within the normal range Conclusions. Our clinical, behavioral, and endocrino- (although often at the lower end), a diagnosis of ISS logic findings in patients with ISS point to an altered in its narrow meaning can be made. In clinical terms, eating behavior that possibly contributes to their short however, these individual diagnostic categories of- stature. Pediatrics 2005;116:e52–e57. URL: www.pediatric- ten can not clearly be distinguished, resulting in combined diagnoses. We therefore chose to summa- rize all these subtypes under the general term and From the Departments of *General Pediatrics and Neonatology and ࿣Pedi- broader definition of ISS. atric Radiology, Center of Child and Adolescent Medicine, Justus Liebig In a previous study from our hospital conducted University, Giessen, Germany; ‡Institute of Medical Biometry and Epide- ϭ miology, Philipps University, Marburg, Germany; §Eli Lilly and Company, between 2000 and 2002 (n 220), 70% of patients Bad Homburg, Germany; ¶Department of General Pediatrics and Neona- with short stature were classified as ISS (wider tology, University of the Saarland, Homburg, Germany; and #Department meaning, see above), with 25% having CDGP, 7% of Child and Adolescent Psychiatry, Rheinische Kliniken Essen, Universita¨t having FSS, 30% having a combination of CDGP and Duisburg-Essen, Essen, Germany. Accepted for publication Dec 29, 2004. FSS, and 8% having ISS in the narrow meaning. The doi:10.1542/peds.2004-1684 large overlap between CDGP and FSS points to a No conflict of interest declared. close relationship between these conditions. It has Address correspondence to Stefan A. Wudy, Center of Child and Adoles- already been hypothesized that CDGP and FSS are cent Medicine, Justus Liebig University, Feulgenstrasse 12, D-35392 Gies- likely to present either a single population with a sen, Germany. E-mail: [email protected] PEDIATRICS (ISSN 0031 4005). Copyright © 2005 by the American Acad- continuum of skeletal age delay and parental stature emy of Pediatrics. or 2 largely overlapping populations.3 Pedigree anal- e52 PEDIATRICS Vol. 116Downloaded No. 1 July from 2005www.aappublications.org/news www.pediatrics.org/cgi/doi/10.1542/peds.2004-1684by guest on September 28, 2021 ysis in patients with CDGP suggested strong familial been a poor eater? (ie, has your child ever eaten or drunk poorly aggregation.4 for at least 4 weeks?)” The options provided for answering this question were “yes,” “no,” “unknown,” or answer denied. Clas- Many pediatric endocrinologists have conceived sification of the children as “poor” or “good” eaters was based on the impression from their daily routine that children their current situation. with CDGP as well as those with FSS or ISS tend to Body height was measured to the nearest 0.1 cm by using an be lean4–6 and are often characterized as poor and Ulm Stadiometer (Busse, Ulm, Germany). A So¨hnle type 7723 fussy eaters by their parents. Most research has con- digital portable scale (capacity of 250 kg, precision of 0.1 kg) was 7 used for measuring body weight. Pubertal development was char- centrated on aspects such as final height or adjuvant acterized according to Tanner stage (pubic hair and breast devel- therapy.8,9 With the exception of a single study of opment in girls, testicular volume and genital development in prepubertal children with ISS,10 in which signifi- boys). Body height and BMI (kg/m2) were compared with the cantly lower body mass index (BMI) values were most current German reference data from Ͼ34 000 children and adolescents.12 Target height was calculated according to Tanner et found, data regarding systematic characterization of al.17 Bone age was assessed independently by 3 pediatric radiol- BMI and eating behavior are lacking. This is surpris- ogists according to the method of Greulich and Pyle18 from radio- ing, because suboptimal nutrition in childhood has graph films of the left hand. Bone-age determination was per- been suggested to contribute to the onset and persis- formed blinded for the patients’ birth date, and the mean of 3 tence of failure to thrive.11 Therefore, it was our aim ratings for each radiograph was used. The interobserver agree- ment was very good as judged from pairwise Bland-Altman bias in the present study to systematically delineate eat- plots,19 in which mean differences between 2 raters were between ing behavior, BMI, and endocrine parameters of 0.5 and 2.3 months and 95% limits of agreement were between 14 body weight regulation. and 24 months. If available, radiograph films from earlier presen- tations at our outpatient clinic were considered as well (1–6 ra- SUBJECTS AND METHODS diograph films were available per child), and the mean and max- imal bone-age retardations at different time points were Study Population calculated. All children who presented between November 2001 and Au- IGF-I, IGFBP-3,20 leptin,21 and total ghrelin (Linco Research Inc, gust 2003 at the endocrine outpatient clinic of the Children’s St Charles, MO) were measured in our endocrinologic laboratory. University Hospital of Giessen (Giessen, Germany) and were di- All other parameters were measured by routine methods in our agnosed as having ISS served as index patients and were prospec- hospital’s laboratory for clinical chemistry. For IGF-I and IGFBP-3, tively enrolled in our study. The term “ISS” is used in this report gender- and age-dependent standard deviation score (SDS) values as the overarching diagnosis, indicating that the etiology of short were calculated,20 and leptin was transformed to SDS values ac- stature in these patients was unknown. It included patients who cording to gender, BMI, and pubertal stage.22 were diagnosed as CDGP, FSS, or a combination of both; however, it excluded patients who were born short for gestational age. Data Analysis Additional index cases were recruited retrospectively from our hospital database and comprised children with ISS who had at- Because our sample comprised both single children and pairs of tended our endocrine outpatient clinic between 1996 and 2001. siblings, not all observations were independent; consequently, The families of the index cases were contacted by phone, and the group means considering all children would give incorrect esti- whole family was invited to participate in the study, which was mates of underlying population means.