Emma V Preston1, Thomas F Webster2, Birgit Claus Henn2, Michael D McClean2, Chris Gennings3, Emily Oken4, Sheryl L Rifas-Shiman5, Elizabeth N Pearce6, Antonia M Calafat7, Abby F Fleisch8, Sharon K Sagiv9. 1. Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA. Electronic address: epreston@hsph.harvard.edu. 2. Department of Environmental Health, Boston University School of Public Health, Boston, MA, USA. 3. Department of Preventive Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 4. Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA; Department of Nutrition, Harvard School of Public Health, Boston, MA, USA. 5. Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA. 6. Section of Endocrinology, Diabetes, and Nutrition, Boston University School of Medicine, Boston, MA, USA. 7. Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA, USA. 8. Center for Outcomes Research and Evaluation, Maine Medical Center Research Institute, Portland, ME, USA. 9. Center for Environmental Research and Children's Health, University of California, Berkeley School of Public Health, Berkeley, CA, USA.
Abstract
BACKGROUND: 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. OBJECTIVES: Estimate associations of exposure to multiple PFAS during early pregnancy with maternal and neonatal thyroid function. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: 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. OBJECTIVES: Estimate associations of exposure to multiple PFAS during early pregnancy with maternal and neonatal thyroid function. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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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