A prospective study of per- and polyfluoroalkyl substances (PFAS), stress, and birth size in a cohort of U.S. Black women

Per- and polyfluoroalkyl substances (PFAS) and psychosocial stress can dysregulate hormonal processes underlying fetal growth. Less is known about the effect of co-exposure to PFAS and stress on birth size. We investigated associations of a preconception mixture of PFAS with birth size and assessed effect modification by perceived stress. We used prospective data from 321 participants from the Study of Environment, Lifestyle, and Fibroids, a cohort of 23-35-year-old women from Detroit, MI who identified as Black/African American. We quantified plasma concentrations of six PFAS in baseline blood samples using online solid-phase extraction-liquid chromatography-isotope dilution tandem mass spectrometry. We assessed experience of perceived stress at baseline using the Perceived Stress Scale-4. Participants reported intervening pregnancies at follow-up visits (at ~ 20, 40, and 60 months). We calculated sex-standardized birthweight-for-gestational-age (BW-for-GA) z-scores from reported birthweight and gestational age at delivery. We employed Bayesian Kernel Machine Regression to estimate associations (βs, with 95% credible intervals [CrI]) of the PFAS mixture with BW-for-GA z-scores and assess effect modification by stress scores, adjusting for confounders. The 90th percentile of the mixture (vs. 50th percentile) was weakly associated with higher BW-for-GA z-scores (β = 0.37, 95% CrI=-0.20, 0.95), driven by perfluorohexanesulfonic acid (PFHxS) and stress scores. PFHxS was weakly associated with higher BW-for-GA z-scores, and this association was stronger at higher levels of perceived stress. A mixture of PFAS and stress scores was weakly associated with higher BW-for-GA z-scores in a cohort of Black women, with evidence of a PFHxS-stress score interaction.