Associations of per- and polyfluoroalkyl substances (PFAS) exposure and thyroid hormone concentration during pregnancy in the LIFECODES cohort

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals widely used in consumer products such as firefighting foams and non-stick cookware. Increasing evidence links PFAS exposure to endocrine disruption and metabolic disease. Pregnancy is a particularly vulnerable period, and disruption of maternal thyroid hormones is of concern given their critical role in metabolism and fetal brain development. METHODS: We examined associations between prenatal PFAS exposure and maternal thyroid hormone concentrations among 434 participants in the LIFECODES birth cohort in Boston. Plasma concentrations of nine PFAS congeners were measured in early pregnancy, and thyroid hormones were assessed repeatedly up to four times across all three trimesters. We evaluated individual PFAS-thyroid hormone associations and conducted mixture analyses to estimate combined effects. Analyses were further stratified by fetal sex and gestational timing of thyroid hormone measurement. RESULTS: Both single-pollutant and mixture analyses revealed fetal sex specific and gestational timing specific associations. For example, in women carrying female fetuses, doubling in PFUA was associated with 7.35% reductions in TSH (95% CI: -13.13, -1.18). Associations between PFAS and T3 were most prominent earlier in pregnancy, whereas associations with TSH tended to emerge from mid-pregnancy onwards. We also observed suggestive mixture effects on T3, FT4, and T3/T4 in gestational timing specific manners. CONCLUSION: Prenatal exposure to individual and multiple PFAS congeners was associated with maternal thyroid hormone disruption, with effects varying by fetal sex and gestational age.