Prenatal exposure to per- and polyfluoroalkyl substances and maternal and neonatal thyroid function in the Project Viva Cohort: A mixtures approach

Maternal and neonatal thyroid function is critical for growth and neurodevelopment. Exposure to individual per- and polyfluoroalkyl substances (PFAS) can alter circulating thyroid hormone levels, but few studies have investigated effects of combined exposure to multiple PFAS.Estimate associations of exposure to multiple PFAS during early pregnancy with maternal and neonatal thyroid function.The study population consisted of 726 mothers and 465 neonates from Project Viva, a Boston, Massachusetts area longitudinal pre-birth cohort. We measured six PFAS [perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoate (PFNA), perfluorohexane sulfonate (PFHxS), 2-(N-ethyl-perfluorooctane sulfonamido)acetate (EtFOSAA), and 2-(N-methyl-perfluorooctane sulfonamido)acetate (MeFOSAA)] and thyroxine (T₄), Free T₄ Index (FT₄I), and thyroid stimulating hormone (TSH) in maternal plasma samples collected during early pregnancy, and neonatal T₄ in postpartum heel sticks. We estimated individual and joint effects of PFAS exposure with thyroid hormone levels using weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR), and evaluated potential non-linearity and interactions among PFAS using BKMR.Higher concentrations of the PFAS mixture were associated with significantly lower maternal FT₄I, with MeFOSAA, EtFOSAA, PFOA, and PFHxS contributing most to the overall mixture effect in BKMR and WQS regression. In infants, higher concentrations of the PFAS mixture were associated with lower T₄ levels, primarily in males, with PFHxS and MeFOSAA contributing most in WQS, and PFHxS contributing most in BKMR. The PFAS mixture was not associated with maternal T₄ or TSH levels. However, in maternal BKMR analyses, ln-PFOS was positively associated with T₄ levels (Δ25ᵗʰ to 75th percentile: 0.21 µg/dL; 95% credible interval: −0.03, 0.47) and ln-PFHxS was associated with a non-linear effect on TSH levels.These findings support the hypothesis that there may be combined effects of prenatal exposure to multiple PFAS on maternal and neonatal thyroid function, but the direction and magnitude of these effects may vary across individual PFAS.