Consistent findings across many studies demonstrate that maternal anxiety during pregnancy can have long-lasting effects on children's physical and neuropsychological development in a manner consistent with fetal programming models. The biological mechanisms accounting for these associations remain uncertain, however. In particular, there is little human research that: a) translates the sizable animal literature showin sex-dependent effects of prenatal physiological stress; and b) addresses the mechanisms underlying recent human findings linking prenatal maternal anxiety and life events stress to neurodevelopmental disorders with significant sex differences (learning difficulties, autism) and sexually-dimorphic physical outcomes (anogenital distance). We propose a prospective longitudinal study starting in the first trimester of pregnancy to test the hypothesis that prenata maternal anxiety alters sex-dependent development in infancy by acting on fetal adrenal androgen pathways. We will do this by recruiting a cohort of 290 pregnant women, following them from the first trimester and regularly collecting behavioral and biological data until the chid 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 both HPA axis and sex steroid hormone pathways, b) intensive interrogation of placental structure and function using the protocols developed from the work with the National Children's Study (NCS); c) repeated assessments of sex-dependent infant physical and neuropsychological outcomes.
The specific aims of the project are to: 1) expand models of maternal psychological anxiety and its biological bases to include multiple hormone pathways; 2) identify evidence of prenatal anxiety-related alterations in adrenal and sex steroid hormone pathways from the placenta and cord blood at birth using our validated 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 anxiety 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 anxiety 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 anxiety during pregnancy and infant anthropometric and neurodevelopmental measures at multiple time points, looking for evidence of anxiety-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 anxiety is transmitted to the fetus and contribute to our understanding of early origins of sex differences in health and development.