Causal Association of Primary Biliary Cholangitis with Adverse Pregnancy and Neonatal Outcomes: A Two-Sample Mendelian Randomization Study.

Background: Primary biliary cholangitis (PBC) is associated with multiple adverse pregnancy events and neonatal outcomes. However, the available observational study evidence results are inconsistent, and causality is unclear. Methods: We used a two-sample Mendelian randomization (MR) analysis to assess the association between PBC and multiple adverse pregnancy events and neonatal outcomes in a European population. Independent SNPs associated with PBC from genome-wide association studies (GWAS) were selected as instrumental variables. The inverse variance weighting (IVW) method was used as the primary analysis method, supplemented by the remaining four MR analysis methods. Heterogeneity and sensitivity analyses of instrumental variables were examined using Cochrane's Q, MR-PRESSO, MR-Egger, and leave-one-out methods. Results: IVW estimates indicated that genetically predicted increased PBC was associated with lower birth weight (OR 0.991, 95% CI 0.983 ~ 0.998, P=0.018), decreased gestational age (OR 0.992, 95% CI 0.987 ~ 0.998, P=0.007), and increased risk of preterm birth (OR 1.043, 95% CI 1.007 ~ 1.081, P=0.019) were associated. For birth weight, the OR estimates obtained by weighted median (OR 0.988, 95% CI 0.980 ~ 0.996, P= 0.006) were consistent with IVW. In addition, no significant causal associations were found between genetically predicted PBC and preeclampsia or eclampsia, miscarriage, placental abruption, gestational diabetes mellitus, and postpartum hemorrhage. Conclusion: Our study reveals that genetically predicted PBC is associated with low birth weight, decreased gestational age, and increased risk of preterm labor in a European population. However, current research does not establish a causal relationship between PBC and adverse pregnancy outcomes.