BACKGROUND: Exposure to perfluoroalkyl substances (PFASs) may increase risk for metabolic diseases; however, epidemiologic evidence is lacking at the present time. Pregnancy is a period of enhanced tissue plasticity for the fetus and the mother and may be a critical window of PFAS exposure susceptibility. OBJECTIVE: We evaluated the associations between PFAS exposures and metabolic outcomes in pregnant women. METHODS: We analyzed 1,240 pregnant women from the Spanish INMA [Environment and Childhood Project (INfancia y Medio Ambiente)] birth cohort study (recruitment period: 2003-2008) with measured first pregnancy trimester plasma concentrations of four PFASs (in nanograms/milliliter). We used logistic regression models to estimate associations of PFASs (log10-transformed and categorized into quartiles) with impaired glucose tolerance (IGT) and gestational diabetes mellitus (GDM), and we used linear regression models to estimate associations with first-trimester serum levels of triglycerides, total cholesterol, and C-reactive protein (CRP). RESULTS: Perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonate (PFHxS) were positively associated with IGT (137 cases) [OR per log10-unit increase=1.99 (95% CI: 1.06, 3.78) and OR=1.65 ( 95% CI: 0.99, 2.76), respectively]. PFOS and PFHxS associations with GDM (53 cases) were in a similar direction, but less precise. PFOS and perfluorononanoate (PFNA) were negatively associated with triglyceride levels [percent median change per log10-unit increase=-5.86% (95% CI: -9.91%, -1.63%) and percent median change per log10-unit increase=-4.75% (95% CI: -8.16%, -0.61%, respectively], whereas perfluorooctanoate (PFOA) was positively associated with total cholesterol [percent median change per log10-unit increase=1.26% (95% CI: 0.01%, 2.54%)]. PFASs were not associated with CRP in the subset of the population with available data (n=640). CONCLUSIONS: Although further confirmation is required, the findings from this study suggest that PFAS exposures during pregnancy may influence lipid metabolism and glucose tolerance and thus may impact the health of the mother and her child. https://doi.org/10.1289/EHP1062.

This study was funded in part by grants from the European Union (FP7-ENV-2011 cod 282957 and HEALTH.2010.2.4.5-1), the Instituto de Salud Carlos III, the Spanish Ministry of Health (Red INMA G03/176; CB06/02/0041; FIS-PI12/01890, FIS-PI041436, FIS- PI081151, FIS-PI06/0867, FIS-PS09/00090; FIS-FEDER: 03/1615, 04/1509, 04/1112, 04/1931, 05/1079, 05/1052, 06/1213, 07/0314, 09/02647, 11/01007, 11/02591, 11/02038, 13/1944, 13/2032, 14/00891, and 14/01687; Miguel Servet-FEDER CP11/0178, MS13/00054, and CPII16/00051; and PFIS-FI14/00099), Generalitat Valenciana (FISABIO: UGP 15-230, UGP-15-244, and UGP-15-249), the Department of Health of the Basque Government (2005111093 and 2009111069), the Provincial Government of Gipuzkoa (DFG06/004 and DFG08/001), the Generalitat de Catalunya-CIRIT (1999SGR 00241), and the National Institutes of Health/National Institute of Environmental Health Sciences (grant number ES021477). This study has been reviewed and approved by the accredited committees of the following institutions: The Municipal Institute of Sanitary Assistance of Barcelona, La Fe University Hospital of Valencia, and The Donostia Hospital.