Maternal cortisol disproportionately impacts fetal growth in male offspring: Evidence from the Philippines

Objectives: Lower birth weight (BW) reoccurs across generations, but the intermediate mechanisms remain poorly understood. One potential pathway involves cortisol, which may be elevated in women born small and in turn could lead to fetal growth restriction in offspring. To test this possibility, we evaluated whether BW predicts hypothalamic-pituitary-adrenal (HPA) function in the nonpregnant state in a cohort of young Filipino women, and whether differences in HPA function predict offspring BW. Methods: Multiple regression relating maternal BW, adult salivary cortisol profiles and recalled offspring BW (N = 488) among participants of the Cebu Longitudinal Health and Nutrition Survey. Results: Maternal BW related inversely to evening cortisol in adulthood (P < 0.04). Maternal BW and evening cortisol were both stronger predictors of male than of female BW (maternal BW: P < 0.0001 for males; P = 0.07 for females; bedtime cortisol: P = 0.003 for males; P = 0.3 for females). Waking and 30-min postwaking cortisol did not predict offspring BW. Controlling for evening cortisol did not diminish the relationship between maternal and offspring BW in males or females. Conclusions: Being born small predicted higher evening cortisol in adulthood among these young mothers. Lower maternal BW and elevated evening cortisol independently predicted giving birth to lower BW offspring, with effects greatest and only significant among males. We speculate that sex differences in sensitivity to maternal stress hormones could help explain the stronger relationships between BW and cardiovascular disease (CVD) risk factors reported among the males in this and other populations.