Size at birth and adrenocortical function in childhood

OBJECTIVE: The mechanisms underlying the association between reduced size at birth and cardiovascular disease and non-insulin-dependent diabetes mellitus in adult life are not known. One possibility is that the intra-uterine environment has permanent effects on the function or activity of the hypothalamo-pituitary-adrenal axis. We tested this by relating size at birth to the urinary excretion of adrenal androgen and glucocorticoid metabolites in a population sample of 9-year-old children. SUBJECTS AND METHODS: One hundred and ninety children (89 boys and 101 girls) of known present height, weight and size at birth collected a 24-hour urine sample. The urinary breakdown products of dehydroepiandrosterone sulphate and of cortisol and cortisone were measured by gas chromatography and their respective breakdown products summed ('adrenal androgen metabolites' and 'glucocorticoid metabolites'). Excretion was expressed in microgram/day. RESULTS: Urinary adrenal androgen metabolite excretion was higher in children who had been light at birth. A 1-kg decrease in birthweight was associated with a 40% (95% CI 9-79%) increase in metabolite excretion. Excretion was positively associated with current weight and age, but the relation with birth weight was independent 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 was higher in children who had been light at birth, but the relation was best described as U-shaped, with the highest average urinary glucocorticoid metabolite excretion being found in children who had been either light or heavy at birth. The U-shaped (quadratic) relation persisted after adjustment for sex and current weight (P for quadratic term 0.006). CONCLUSION: These findings suggests that the intra-uterine environment, as measured by fetal size at birth, has long-lasting effects on the function of the hypothalamo-pituitary-adrenal axis.