Unveiling the truth: Pathogen infections linked to miscarriage: A STROBE-Compliant Mendelian randomization study

Miscarriage represents a prevalent yet insufficiently studied adverse pregnancy outcome. The definitive causal links between various pathogens and miscarriage remain to be established. To investigate the causal connections between pathogen infections and miscarriage, we utilized a two-sample bidirectional Mendelian randomization (MR) analysis. We sourced genome-wide association studies data on pathogen infections from the UK Biobank, which included serological markers for infectious diseases and comprehensive whole-genome genetic information from approximately 10,000 individuals. Additionally, genome-wide association studies data on miscarriages were collected from 3 distinct European populations for our analysis. The MR analysis was primarily conducted using the inverse variance weighted method, complemented by Bayesian weighted MR and the weighted median method for robustness. To ensure the reliability of our findings, we performed heterogeneity and pleiotropy tests, leave-one-out sensitivity analyses, and a meta-analysis. Our extensive research has identified a causal association between miscarriage and infections by several human herpesviruses (HHV-1, HHV-3, HHV-4, HHV-6, and HHV-7), polyomaviruses (BK, JC, and Merkel cell polyomaviruses), and Chlamydia trachomatis (inverse variance weighted, P < .05). Notably, a meta-analysis of the integrated data highlighted the particularly high accuracy and consistency of the association with Merkel cell polyomavirus. Our MR analysis has clarified the causal relationships between specific pathogen infections and miscarriage, providing a critical foundation for the prevention and treatment of this adverse pregnancy outcome.