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

Area of Science:

• Reproductive Health
• Infectious Diseases
• Genetic Epidemiology

Background:

• Miscarriage is a common adverse pregnancy outcome with unclear causes.
• Establishing definitive causal links between specific pathogens and miscarriage is crucial for public health.

Purpose of the Study:

• To investigate the causal relationships between various pathogen infections and miscarriage using a robust analytical approach.
• To identify specific infectious agents that contribute to the risk of miscarriage.

Main Methods:

• Conducted a two-sample bidirectional Mendelian randomization (MR) analysis.
• Utilized genome-wide association studies (GWAS) data for pathogen infections (UK Biobank) and miscarriage (3 European cohorts).
• Employed inverse variance weighted, Bayesian weighted MR, and weighted median methods, with sensitivity analyses for reliability.

Main Results:

• Identified causal associations between miscarriage and infections with human herpesviruses (HHV-1, -3, -4, -6, -7), polyomaviruses (BK, JC, Merkel cell), and Chlamydia trachomatis.
• Merkel cell polyomavirus showed a particularly consistent and accurate association in meta-analysis.
• Confirmed specific pathogen-miscarriage causal links through rigorous MR analysis.

Conclusions:

• Specific viral and bacterial infections are causally linked to miscarriage.
• Findings provide a foundation for targeted prevention and treatment strategies for miscarriage.
• Highlights the importance of investigating infectious agents in adverse pregnancy outcomes.