Associations of Per- and Polyfluoroalkyl Substances (PFAS) With Glucose Tolerance During Pregnancy in Project Viva

Abstract Context Per- and polyfluoroalkyl substances (PFAS) exposure may alter glucose homeostasis. Research on PFAS exposure and glucose tolerance during pregnancy is limited. Objective The objective of this work is to estimate associations between first-trimester plasma PFAS concentrations and glucose tolerance assessed in late second pregnancy trimester. Design, Setting, Participants, and Main Outcome Measures Pregnant women (n = 1540) enrolled in Project Viva in 1999 to 2002 provided first-trimester plasma samples analyzed for 8 PFAS. At approximately 28 weeks’ gestation, women completed 1-hour nonfasting, 50-g oral glucose challenge tests (GCTs); if abnormal, women completed subsequent 3-hour oral glucose tolerance tests (OGTTs) to screen for gestational diabetes mellitus (GDM). We assessed both continuous GCT glucose levels and 4 categories of glucose tolerance (normal glycemia [reference], isolated hyperglycemia, impaired glucose tolerance, GDM). We used multinomial logistic regression to estimate associations of PFAS with glucose tolerance categories. We used multivariable linear regression and Bayesian kernel machine regression (BKMR) to assess individual and joint effects of PFAS on continuous GCT glucose levels, respectively. We evaluated effect modification by maternal age and race/ethnicity. Results PFAS were not associated with glucose tolerance categories. In BKMR analyses, we observed a positive association between ln-perfluorooctane sulfonate (PFOS) and glucose levels (Δ25th to 75th percentile: 6.2 mg/dL, 95% CI, 1.1-11.3) and an inverse-U shaped association between 2-(N-perfluorooctane sulfonamide) acetate and glucose levels. Individual linear regression results were similar. We found suggestive evidence that associations varied by age and racial/ethnic group. Conclusion Certain PFAS may alter glucose homeostasis during pregnancy, but may not be associated with overt GDM.