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

By Emma V Preston, Thomas F Webster, Birgit Claus Henn, Michael D McClean, Chris Gennings, Emily Oken, Sheryl L Rifas-Shiman, Elizabeth N Pearce, Antonia M Calafat, Abby F Fleisch, and Sharon K Sagiv
Environ Int
April 21, 2020
DOI: 10.1016/j.envint.2020.105728


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 (T), Free T Index (FTI), and thyroid stimulating hormone (TSH) in maternal plasma samples collected during early pregnancy, and neonatal T 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 FTI, 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 T 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 T or TSH levels. However, in maternal BKMR analyses, ln-PFOS was positively associated with T levels (Δ25 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.

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