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Size at birth and adrenocortical function in childhood
P M Clark1, P C Hindmarsh, A W Shiell
1MRC Environmental Epidemiology Unit, University of Southampton, UK.
Insights
Fetal size at birth impacts adult health. Lower birth weight is linked to higher adrenal androgen metabolite excretion in children, suggesting lasting effects of the intra-uterine environment on the hypothalamo-pituitary-adrenal axis.
Area of Science:
- Endocrinology
- Developmental Biology
- Public Health
Background:
- Reduced size at birth is associated with increased risk of cardiovascular disease and non-insulin-dependent diabetes mellitus in adulthood.
- The intra-uterine environment may permanently alter hypothalamo-pituitary-adrenal (HPA) axis function, mediating this association.
Purpose of the Study:
- To investigate the relationship between size at birth and the function of the HPA axis in childhood.
- To assess urinary excretion of adrenal androgen and glucocorticoid metabolites in relation to birth weight.
Main Methods:
- 190 children (9-year-olds) provided 24-hour urine samples.
- Urinary breakdown products of dehydroepiandrosterone sulfate (adrenal androgen metabolites) and cortisol/cortisone (glucocorticoid metabolites) were measured.
- Gas chromatography was used to quantify metabolite excretion in microgram/day.
Main Results:
- Higher urinary adrenal androgen metabolite excretion was observed in children with lower birth weights (40% increase per 1-kg decrease).
- This association was independent of current weight, age, and sex.
- Glucocorticoid metabolite excretion showed a U-shaped relationship with birth weight, being highest in children who were light or heavy at birth, persisting after adjustments.
Conclusions:
- Fetal size at birth, a proxy for the intra-uterine environment, has enduring effects on HPA axis function.
- These findings provide insights into the developmental origins of adult disease risk.
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.