Associations of PFAS exposure with obstetric and birth outcomes in the Japan Environment and Children’s Study (JECS): Is maternal endometriosis an effect modifier?

Per- and polyfluoroalkyl substances (PFAS) are reportedly associated with adverse obstetric outcomes, including premature labor and gestational diabetes. We aimed to evaluate associations of maternal PFAS exposure with obstetric and birth outcomes in the Japan Environment and Children's Study cohort. This study included 23,596 participants with first-trimester plasma samples analyzed for PFAS concentrations by liquid chromatography-tandem mass spectrometry. Outcome data were transcribed from physicians' questionnaires at birth, and covariates from maternal or prenatal questionnaires. Adjusted odds ratios with 95 % confidence intervals (CIs) were calculated for exposure to individual PFAS and several outcomes using binary logistic regression; B coefficients with 95 % CIs were obtained for gestational weight gain (GWG). The Benjamini-Hochberg method controlled the false discovery rate. A quantile g-computation model assessed associations between PFAS mixtures and outcomes. Significant associations were found between exposure to eight PFAS and 11 outcomes, including placenta previa, cesarean delivery, GWG, post-term birth, and threatened abortion. Although the associations were usually positive, negative associations were observed between certain PFAS congeners and intrauterine growth restriction, non-reassuring fetal status, term premature rupture of membranes, and threatened premature labor. PFAS exposure during pregnancy showed modest positive and negative associations with obstetric and birth outcomes. PFAS mixtures were positively associated with cesarean delivery, neonatal complications, and post-term birth, and negatively with GWG. Associations of PFAS exposure with neonatal complications, threatened premature labor, threatened abortion and cesarean delivery varied between women with and without endometriosis. Despite restrictions on many PFAS, they may still affect obstetric health.