Associations of Allopregnanolone and Related Steroid Hormones with Prenatal Psychosocial Distress in the Healthy Start Cohort

Psychosocial distress is associated with adverse perinatal outcomes, yet its biological correlates remain incompletely understood. We evaluated associations of prenatal psychosocial distress with allopregnanolone (ALLO) and related steroids, and assessed race/ethnicity as a potential effect modifier, using data from 237 participants from the Healthy Start Study. We selected participants based on high distress (Edinburgh Perinatal Depression Scale [EPDS] >=13 or EPDS-3A >=7; n = 57) or low distress (EPDS <4 and EPDS-3A <2; n = 180). We quantified ALLO, progesterone, pregnanolone, cortisol, and cortisone in maternal serum using HPLC-MS/MS at two timepoints in pregnancy for each participant, (median ~17 and ~27 weeks gestation; range: 10-34 weeks). We modeled the relationship between high vs. low prenatal distress with repeated measures of the steroid hormones using linear mixed-effects models. We found that ALLO was 20.6% lower (95% CI: -30.9%, -8.7%) in high-distress individuals after adjusting for maternal age, fetal sex, smoking and gestational age at blood draw, with no evidence of effect modification by race/ethnicity. However, this association attenuated after additional adjustment for sociodemographic characteristics. Several ALLO-related ratios were lower with high distress, but only ALLO-to-progesterone remained significant across models. These findings suggest that associations between psychosocial distress and circulating ALLO concentrations during pregnancy are influenced by social and structural factors, with the exception of the ALLO-to-progesterone ratio, which may capture aspects of neurosteroid metabolism more closely linked to prenatal psychosocial distress.