ABSTRACT

Spontaneous miscarriage (SM) is a common pregnancy complication. Although clinical factors are associated with SM, establishing causality is challenging. Mendelian randomization (MR) helps evaluate the causal effects of exposure variables. This study systematically reviewed 31 MR studies performed in SM, identifying causal relationships between SM and smoking, obesity, insomnia, rheumatoid arthritis, and immune-related factors. Smoking initiation and insomnia were identified as risk factors for SM. Coffee consumption showed no causal association with SM risk. Inconsistent evidence was reported for alcohol intake, BMI, depression, and RA regarding their causal relationships with SM. Smoking initiation, specific cytokines (eg, IL-12, TNF-β), and immune cells (eg, CD4+ T cells) demonstrated causal associations with the number of SM. Notably, key SNPs like rs13261666 and rs7127595 played significant roles in MR analyses due to their strong genetic associations with risk factors. Future research should further investigate the mechanistic pathways linking these genetic variants to SM, aiming to provide precise guidance for clinical prevention and treatment. Additionally, inconsistencies in MR results may stem from differences in data sources, SNP selection criteria, and statistical methodologies, indicating the importance of improving data consistency and standardizing analytical approaches in future research

‍