Associations between maternal prenatal cortisol and fetal growth are specific to infant sex: Findings from the Wirral Child Health and Development Study

Recent findings highlight that there are prenatal risks for affective disorders that are mediated by glucocorticoid mechanisms, and may be specific to females. There is also evidence of sex differences in prenatal programming mechanisms and developmental psychopathology, whereby effects are in opposite directions in males and females. As birth weight is a risk for affective disorders, we sought to investigate whether maternal prenatal cortisol may have sex-specific effects on fetal growth. The Wirral Child Health and Development Study (WCHADS) cohort (n=1233) included a stratified subsample (n=241) who provided maternal saliva samples, assayed for cortisol, at home over two days at 32 weeks gestation (on waking, 30-minutes post-waking, and during the evening). Measures of infant birth weight (corrected for gestational age) were taken from hospital records. General population estimates of associations between variables were obtained using inverse probability weights. Maternal log of the area under the curve (LogAUC) cortisol predicted infant birth weight in a sex-dependent manner (interaction term p=0.040). There was a positive association between maternal prenatal cortisol in males, and a negative association in females. A sex-interaction in the same direction was evident when using the waking (p=0.010), and 30-minute post waking (p=0.013) cortisol measures, but not the evening measure. There was no interaction between prenatal cortisol and sex to predict gestational age. Our findings add to an emerging body of literature that suggests that there may be sex-specific mechanisms that underpin fetal programming. Further understanding of these mechanisms is important for tailoring intervention and prevention strategies.