Associations of Per- and Polyfluoroalkyl Substances With Maternal Early Second Trimester Metabolic Biomarkers

Objectives: Pregnant women are exposed to persistent metabolic disruptors called per- and polyfluoroalkyl substances (PFAS) via drinking water, food products from animals, and household items. PFAS have been linked to poor fetal health and pregnancy outcomes, but the underlying mechanisms are unclear. Because pregnant women are jointly exposed to several highly correlated PFAS, we evaluated associations of a PFAS mixture with maternal metabolic biomarkers critical for maternal adaptations in pregnancy. Methods: Pregnant Illinois women (n=452) provided fasted blood samples at 17 weeks gestation, from which we measured plasma glucose, insulin, C-peptide, insulin-like growth factor 1, adiponectin, leptin, triglycerides, free fatty acids, total cholesterol, and high-density lipoprotein (HDL) cholesterol. We calculated homeostatic model assessment for insulin resistance (HOMA-IR), low-density lipoprotein cholesterol, and very low-density lipoprotein. We also quantified serum PFAS, including perfluorodecanoic acid (PFDeA) and perfluoroundecanoic acid (PFUdA). We evaluated the covariate-adjusted joint association of ln-transformed PFAS as a mixture with each ln-transformed metabolic biomarker using quantile-based g-computation that can evaluate cumulative associations and identify the most important contributors to the PFAS mixture. Results: In a sample of metabolically healthy women with PFAS levels similar to a representative sample of U.S. women, exposure to the PFAS mixture was associated with lower insulin, HOMA-IR, and leptin, but higher HDL cholesterol in early second trimester. Specifically, each 10% increase in the PFAS mixture was associated with 12.8% lower insulin (95% confidence interval (CI): -20.3, -4.5) and 13.3% lower HOMA-IR (95%CI: -20.9, -4.9), with PFDeA driving the mixture association. Additionally, each 10% increase in the PFAS mixture was associated with lower leptin (β: -3.9; 95%CI: -7.2, -0.6) and higher HDL cholesterol (β: 2.8; 95%CI: 1.8, 3.9), with PFUdA contributing most to each mixture association. Conclusions: Given the role of insulin, leptin, and HDL in maternal adaptation in early pregnancy to support fetal growth, further investigation is needed to identify potential consequences of our findings for maternal and child health outcomes. Funding Sources: NIEHS, EPA, NICHD, NIHOD, USDA NIFA, NIDDK.