Early Pregnancy Plasma Per- and Polyfluoroalkyl Substances (PFAS) and Maternal Midlife Adiposity.

ABSTRACT

CONTEXT Evidence suggests that exposure to per- and polyfluoroalkyl substances (PFAS) increases the risk of developing cardiometabolic disease risk factors. Limited research has evaluated associations between PFAS, assessed during pregnancy, a sensitive window for maternal endocrine effects, and long-term maternal adiposity. OBJECTIVE: Estimate associations of early pregnancy measures of individual PFAS, and PFAS mixtures, with maternal adiposity in midlife. METHODS: We studied 547 Project Viva participants with measures of early pregnancy (mean gestation 10.0 weeks; mean age 32.5 years) plasma concentrations of 6 PFAS and midlife adiposity outcomes (mean follow-up 17.7 years; mean age 50.7 years), including weight, waist circumference (WC), trunk fat mass (TFM), and total body fat mass (TBFM). We used linear regression and Bayesian Kernel Machine Regression (BKMR). RESULTS: Linear regression estimated higher midlife weight per doubling of perfluorooctane sulfonate (PFOS) (3.8 kg [95% CI 1.6, 5.9]) and 2-(N-ethyl-perfluorooctane sulfonamido) acetate (2.3 kg [95% CI 0.9, 3.7]). BKMR analyses of single PFAS plasma concentrations (comparing the 25th percentile concentration to the 75th percentile) showed a positive association between PFOS and midlife adiposity (weight 7.7 kg [95% CI 4.0, 11.5]; TFM 1.2 kg [95% CI 0.0, 2.3]; TBFM 3.0 kg [95% CI 0.8, 5.2]), but inverse associations with perfluorononanoate (weight -6.0 kg [95% CI -8.5, -3.5]; WC -1.8 cm [95% CI -3.2, -0.3]; TFM -0.8 kg [95% CI -1.5, -0.1]; TBFM -1.4 kg [95% CI -2.7, -0.3]) and perfluorohexane sulfonate (TFM -0.8 kg [95% CI -1.5, -0.1]; TBFM -1.4 kg [95% CI -2.6, -0.2]). No associations were observed with the overall PFAS mixture. CONCLUSION: Select PFAS, assessed in pregnancy, may differentially affect maternal midlife adiposity, influencing later-life maternal cardiometabolic health.