Maternal per- and polyfluoroalkyl substances exposure and the co-occurrence of gestational diabetes mellitus and preeclampsia/eclampsia: a nested case-control study.

OBJECTIVE: Few studies have investigated the relationship between maternal exposure to per- and polyfluoroalkyl substances (PFAS) and the co-occurrence of gestational diabetes mellitus (GDM) and hypertensive disorders of pregnancy, particularly preeclampsia/eclampsia (PE/E). The present study aimed to explore whether PFAS exposure is associated with the co-occurrence of GDM and PE/E. METHODS: This study enrolled 333 pregnant women diagnosed with both GDM and PE/E, and 360 healthy controls. First-trimester plasma concentrations of 18 PFAS were determined by ultra-high performance liquid chromatography-tandem triple quadrupole mass spectrometry (UPLC-MS/MS). The associations of individual and combined maternal PFAS exposure with the odds of co-occurrence were assessed by restricted cubic spline (RCS) analysis, multivariable logistic regression, and Bayesian kernel machine regression (BKMR). RESULTS: The concentrations of perfluoroheptanoic acid (PFHpA), perfluorobutanesulfonic acid (PFBS), and perfluorotridecanoic acid (PFTrDA) differed significantly between the two groups; however, after false discovery rate (FDR) correction, only PFHpA and PFTrDA remained significantly different. RCS analysis showed significant associations of PFHpA and PFBS with the co-occurrence (P overall = 0.026 and 0.014, respectively), without nonlinearity (P non-linear = 0.619 and 0.206, respectively); However, the overall associations were no longer significant after FDR correction. In multivariable logistic regression models, after FDR correction, each log10-unit increment in PFHpA and PFBS was significantly associated with increased odds of the co-occurrence, with adjusted odds ratios (aORs) of 2.439 (95% CI: 1.269-4.689) and 1.688 (95% CI: 1.161-2.453), respectively. For perfluoroheptane sulfonic acid (PFHpS), a positive association was also observed (aOR = 1.712, 95% CI: 1.051-2.788); however, the association was not significant after FDR correction. BKMR analysis revealed a positive association between PFAS mixture exposure and the co-occurrence, with the association strengthening progressively at higher mixture concentrations. Among the individual PFAS, PFHpA, PFBS and PFHpS exhibited positive trends, whereas PFTrDA displayed inverse trends. CONCLUSION: PFHpA, PFBS, and the 10 PFAS mixture were all positively associated with increased odds of co-occurrence of GDM and PE/E.