Association between exposure to perfluoroalkyl substances (PFASs) and risk of hyperemesis gravidarum

The fluctuation of endocrine hormones during early pregnancy plays an important role in the pathogenesis of hyperemesis gravidarum (HG). As an endocrine disrupting chemical (EDC), perfluoroalkyl substances (PFASs) exert an impact on pregnancy-related complications by altering hormone balances throughout gestation. Despite this potential impact, the relationship between serum PFAS levels in early pregnancy and the risk of HG has not been previously investigated. A total of 98 HG cases and 495 controls were included in this study from the Xi'an Birth Cohort Study. In total, serum levels of 10 PFASs were measured using High Performance Liquid Chromatography with tandem Mass Spectrometry (HPLC-MS/MS) during early pregnancy. Binary logistic models were applied to evaluate the associations between individual PFAS levels and HG. Weighted quantile sum (WQS) regression models and Bayesian kernel machine regression (BKMR) models were performed to test the overall effect of the PFAS mixture on HG. After adjusting for confounding variables, the highest tertile concentrations of perfluoroundecanoic acid (PFUnDA) (OR: 3.49, 95 %CI: 1.31-9.29), and perfluorododecanoic acid (PFDoA) (OR: 3.13, 95 % CI: 1.40-6.98) were significantly associated with a higher risk of HG, while highest tertile of perfluorohexanoic acid (PFHxA) (OR: 0.34; 95 % CI: 0.16-0.73), and PFOS (OR: 0.35; 95 % CI: 0.13-0.97) were inversely associated with HG. The WQS index showed a positive correlation with HG risk (β = 0.80; 95 % CI: 0.02, 1.57), with notable contributions from PFDoA (0.952), PFUnDA (0.159), and perfluorobutanoic acid (PFBA) (0.146). In addition, the joint effect of the PFAS mixture was positively associated with HG, with PFDoA (posterior inclusion probability (PIP) = 0.78) and PFUnDA (PIP = 0.75) being identified as the primary contributors. Our findings indicate that exposure to PFAS mixture during early pregnancy was associated with an increased risk of HG, with PFDoA and PFUnDA being the major contributors.