Consistent findings across many studies demonstrate that maternal stress during pregnancy can have long-lasting effects on children's physical and neuropsychological development in a manner consistent with a programming mechanism. The biological mechanisms accounting for these associations remain uncertain, however. Particularly missing is human research that a) translates the sizable animal literature showing sex- dependent effects of prenatal stress and b) considers mechanisms underlying recent human findings linking prenatal maternal stress to sexually-dimorphic physical outcomes (anogenital distance) and neurodevelopmental disorders with significant sex differences (learning difficulties, autism). We propose a prospective longitudinal study starting in the first trimester to test the hypothesis that prenatal maternal stress may alter sex-dependent development in infancy by acting on fetal adrenal androgen pathways. We will do this by recruiting a cohort of 240 pregnant women, following them from the first trimester and regularly collecting behavioral and biological data until the child is 15 months of age using procedures for recruitment and retention successfully applied in prior cohort studies. The research design includes several important innovations in this growing field of study, including a) detailed data on stress hormones alongside sex steroid hormones sampled from multiple sources, b) intensive interrogation of placental structure and function using the protocols developed from the work with the National Children's Study (NCS); c) multiple assessments of infant physical and neuropsychological outcomes for which early emerging sex differences have been reliably documented.
The specific aims of the project are to: 1) investigate maternal psychological stress and the stress hormone cortisol in relation to biomarkers of fetal and placental hormone activity, in each trimester of pregnancy; 2) identify evidence of prenatal stress-related alteratios in stress and sex steroid hormone pathways from the placenta and cord blood at birth using our established NCS protocols; 3) integrate maternal and placental biomarkers in predicting sex-dependent physical, neurocognitive, and social behavior measures at birth, 9 and 15 months. This line of research will complement and extend existing work by clarifying the biological mechanisms by which maternal stress is communicated to the fetus and improving our understanding of the etiology of sex differences in health and disease.
This project explores the hypothesis that exposure to prenatal maternal stress programs sex-dependent development by altering fetal adrenal androgen production. To test this hypothesis; in a new pregnancy cohort; we will examine the relationship between maternal stress during pregnancy and infant anthropometric and neurodevelopmental measures at multiple time points; looking for evidence of stress-related changes in the sex steroid biosynthesis pathway across multiple tissues (maternal serum; placental tissue; and cord blood). This study has important clinical and public health ramifications in that it may illuminate the mechanisms by which maternal stress is transmitted to the fetus and contribute to our understanding of early origins of sex differences in health and development.
