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Opposing Influences of Prenatal and Postnatal Weight Gain on Adrenarche in Normal Boys and Girls

Department of Paediatrics (K.K.O., C.J.P., D.B.D.), University of Cambridge, Cambridge CB2 2QQ, United Kingdom; Hormonal Laboratory (N.P.), Hospital Materno-Infantil Vall d’Hebron, E-08035 Barcelona, Spain; Unit of Paediatric and Perinatal Epidemiology (R.J., A.R.N., ALSPAC Study Team), University of Bristol, Bristol BS8 1TQ, United Kingdom; Department of Chemical Pathology (J.W.H.), University College London Hospitals, London W1T 4JF, United Kingdom; Department of Paediatrics (F.d.Z.), University of Leuven, B-3000 Leuven, Belgium; and Endocrine Unit (L.I.), Hospital Sant Joan de Déu, University of Barcelona, E-08950 Barcelona, Spain

Address all correspondence and requests for reprints to: Professor David B. Dunger, Department of Pediatrics, University of Cambridge, Addenbrooke’s Hospital, Level 8, Box 116, Cambridge CB2 2QQ, United Kingdom. E-mail: dbd25{at}cam.ac.uk.

Associations between low birth weight and higher adrenal androgen secretion before puberty have yet only been reported in case-control studies in girls. We examined the influence of birth weight and early postnatal weight gain on overnight-fasting adrenal androgen and cortisol levels in 770 children from a large normal United Kingdom birth cohort at age 8 yr. In univariate analyses, adrenal androgen levels were inversely related to birth weight SD score in each sex [dehydroepiandrosterone sulfate in boys: regression coefficient (B) = –2.5 µg/dl/SD; 95% confidence interval (CI), –4.7 to –0.2; in girls: B = –3.8 µg/dl/SD; 95% CI, –6.2 to –1.4; androstenedione in boys: B = –0.15 nmol/liter/SD, 95% CI, –0.25 to –0.6; in girls: B = –0.13 nmol/liter/SD; 95% CI, –0.24 to –0.02). In multivariate analyses, both lower birth weight and larger current body weight predicted higher adrenal androgen levels (P < 0.005 for all comparisons). Allowing for current weight, children who showed rapid postnatal weight gain between 0 and 3 yr had higher dehydroepiandrosterone sulfate (P = 0.002) and androstenedione (P = 0.004) levels at 8 yr. In contrast, cortisol levels were unrelated to birth weight or current body size. In summary, the relationship between lower birth weight and higher childhood adrenal androgen levels was continuous throughout the range of normal birth weights, and was similar in boys and girls. Adrenal androgen levels were highest in small infants who gained weight rapidly during early childhood. We suggest that higher adrenal androgen secretion could contribute to links between early growth and adult disease risks, possibly by enhancing insulin resistance and central fat deposition.

This work would not have been undertaken without the financial support of the Medical Research Council, the Wellcome Trust, the United Kingdom Department of Health, the Department of the Environment, the Department for Education and Employment, the National Institutes of Health, and a variety of medical research charities and commercial companies. ALSPAC is part of the World Health Organization-initiated European Longitudinal Study of Parents and Children. K.O. was supported by a Medical Research Council Clinical Training Fellowship. D.D. is supported by the Wellcome Trust and the Juvenile Diabetes Research Foundation. L.I. was supported by a Visiting Fellowship from the European Society for Pediatric Endocrinology. F.d.Z. is a Clinical Research Investigator of the Fund for Scientific Research, Flanders, Belgium.

Abbreviations: ALSPAC, Avon Longitudinal Study of Parents and Children; B, regression coefficient; BMI, body mass index; CI, confidence interval; CV, coefficient of variation; DHEAS, dehydroepiandrosterone sulfate.

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