Causal Relationship between Multiple Autoimmune Diseases and Pregnancy Loss: A Two-Sample Mendelian Randomization Study

Abstract

Background Although systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) have been clinically confirmed to cause pregnancy loss and effective clinical treatment and nursing programs have been proposed to greatly improve pregnancy outcomes, the relationship between other types of autoimmune diseases (ADs) and pregnancy loss remains unclear due to inconsistent conclusions from existing observational studies. This has hindered the formation of clinical consensus and the implementation of comprehensive management for pregnant women with ADs. To address this gap, we executed a two-sample mendelian randomization(MR) approach intending to assess the potential causal impact of 29 ADs on 7 types of pregnancy loss. Results The two-sample MR investigations with inverse variance weighted(IVW) approach revealed strong causal relationship between broadly defined ADs and stillbirth, spontaneous miscarriage, or termination [Odd ratios (ORs), 1.00846; 95% confidence intervals (CIs), 1.00095–1.01602; p value = 0.027]. Type 1 diabetes (T1D) exhibited a positive link with the number of spontaneous miscarriages [OR, 1.00709; 95%CI, 1.00134–1.01288; p value = 0.016]. Meanwhile, autoimmune hypothyroidism was strongly linked to ever had stillbirth, spontaneous miscarriage, or termination [OR, 1.00413; 95%CI, 1.00043–1.00784; p value = 0.028]. Additionally, crohn's disease (CD), a gastrointestinal immune disease, exhibited a significantly positive correlation with spontaneous abortion [OR, 1.00036; 95%CI, 1.00012–1.00059; p value = 0.003]. Interestingly, we observed that rheumatoid arthritis (RA) indicated a negative connection with spontaneous abortion [OR, 0.99953; 95%CI, 0.99909–0.99997; p value = 0.036]. Conclusion The findings of this study implied a causal association between different ADs and pregnancy loss, thus advancing our comprehension of the ADs-mediated etiology and pathogenesis of pregnancy loss.