Do measures of general versus pregnancy-related anxiety have distinct maternal-fetal-placental biology?

Anxiety during pregnancy is a clinical and public health concern that has been linked to adverse maternal and perinatal outcomes and, via developmental programming, altered fetal biology and behavior with lasting effects on health and development. Two anxiety phenotypes, pregnancy-related anxiety (PrA) and general prenatal anxiety (GenA), have been identified as showing distinct phenotypic patterns and differential associations with child health outcomes. This study tests the novel corollary hypothesis that these phenotypes can be differentiated according to maternal-fetal-placental biological pathways. Prenatal anxiety, stress physiology (diurnal cortisol and corticotropin releasing hormone), sex steroid, and placental biomarker data were collected from N = 317 participants in a prospective longitudinal pregnancy cohort study. We found clear evidence for phenotypic distinctions between pregnancy-related and general anxiety but modest to weak evidence for differential associations with maternal-fetal-placenta biology; generally stronger associations were obtained between maternal-fetal-placenta biology and pregnancy-related compared to general anxiety. Specifically, PrA - and not GenA - was associated with overall cortisol concentration (β = -0.20, SE = 0.06, p < .001) and a flatter diurnal slope (β = 0.02, SE = 0.01, p < .001). Similarly, only PrA was significantly associated with lower estrone (β = -0.01, SE = 0.006, p < .05), estradiol (β = -0.009, SE = 0.004, p < .05), and total testosterone (β = -0.02, SE = 0.009, p < .05) levels. The stronger associations between PrA and maternal-fetal-placenta biology may reflect its comparatively greater experiential and clinical relevance, which may have implications for prenatal intervention.