Potential causal associations between perfluoroalkyl substances exposure and adverse pregnancy outcomes: A bidirectional two-sample mendelian randomization study

Maternal exposure to per- and polyfluoroalkyl substances (PFASs) has been linked to adverse pregnancy outcomes (APOs). Nonetheless, the genetic causality underlying this association remains unknown. This research employed a bidirectional two-sample Mendelian randomization (MR) to investigate the potential causal associations between PFASs exposure and APOs risk. PFASs data were sourced from the GWAS Catalog, and APOs data were retrieved from the FinnGen consortium. Causal estimation primarily employed inverse variance weighting, with Cochran's Q test for instrumental variable heterogeneity, and MR-Egger, MR-PRESSO, and leave-one-out tests for sensitivity analyses. The possibility of reverse causality was investigated through reverse MR. MR evidence revealed a notable correlation between perfluorooctanoic acid (PFOA) and abruptio placentae (OR=1.498, P=0.026), as well as short gestation and low birth weight (OR=1.720, P=0.013). Exposure to perfluorooctanesulfonic acid (PFOS) increased the risk of preeclampsia or eclampsia (OR=1.128, P=0.030) and gestational hypertension (OR=1.076, P=0.049), but decreased the risk of premature rupture of membranes (OR=0.916, P=0.033). The results obtained were consistent across various sensitivity analyses. Reverse MR results was negative. These findings may provide a reference for prevention strategies and intervention measures for PFASs exposure and APOs, and provide a framework for studying the causal effects of environmental pollutant exposure and human diseases.