SIZE AT BIRTH AND ADRENOCORTICAL FUNCTION IN CHILDHOOD

OBJECTIVE The mechanisms underlying the association between reduced si ze at birth and cardiovascular disease and non-insulin-dependent diabe tes mellitus in adult life are not known. One possibility is that the intra-uterine environment has permanent effects on the function or act ivity of the hypothalamopituitary-adrenal axis. We tested this by rela ting size at birth to the urinary excretion of adrenal androgen and gl ucocorticoid metabolites in a population sample of g-year-old children . SUBJECTS AND METHODS One hundred and ninety children (89 boys and 10 1 girls) of known present height, weight and size at birth collected a 24-hour urine sample. The urinary breakdown products of dehydroepiand rosterone sulphate and of cortisol and cortisone were measured by gas chromatography and their respective breakdown products summed ('adrena l androgen metabolites' and 'glucocorticoid metabolites'). Excretion w as expressed in mu g/day. RESULTS Urinary adrenal androgen metabolite excretion was higher in children who had been light at birth, A 1-kg d ecrease in birthweight was associated with a 40% (95% CI 9-79%) increa se in metabolite excretion, Excretion was positively associated with c urrent weight and age, but the relation with birth weight was independ ent of weight, age or sex. Urinary glucocorticoid metabolite excretion was positively associated with current weight, but not independently with age. The urinary excretion of total glucocorticoid metabolites wa s higher in children who had been light at birth, but the relation was best described as U-shaped, with the highest average urinary glucocor ticoid metabolite excretion being found in children who had been eithe r light or heavy at birth. The U-shaped (quadratic) relation persisted after adjustment for sex and current weight (P for quadratic term 0.0 06). CONCLUSION These findings suggests that the intrauterine environm ent, as measured by fetal size at birth, has tong-lasting effects on t he function of the hypothalamo-pituitary-adrenal axis.