Association between Thiopurines Use and Pregnancy Outcomes in Female Patients with Inflammatory Bowel Disease: A Meta-Analysis

Background: Conflicting data exist regarding the influence of thiopurines exposure on adverse pregnancy outcomes in female patients with inflammatory bowel disease (IBD). Objective: The aim of this study was to provide an up-to-date and comprehensive assessment of the safety of thiopurines in pregnant IBD women. Methods: All relevant articles reporting pregnancy outcomes in women with IBD received thiopurines during pregnancy were identified from the databases (PubMed, Embase, Cochrane Library, and ClinicalTrials.gov) with the publication data up to April 2020. Data of included studies were extracted to calculate the relative risk (RR) of multiple pregnancy outcomes: congenital malformations, low birth weight (LBW), preterm birth, small for gestational age (SGA), and spontaneous abortion. The meta-analysis was performed using the random-effects model. Results: Eight studies matched with the inclusion criteria and a total of 1201 pregnant IBD women who used thiopurines and 4189 controls comprised of women with IBD received drugs other than thiopurines during pregnancy were included. Statistical analysis results demonstrated that the risk of preterm birth was significantly increased in the thiopurine-exposed group when compared to IBD controls (RR, 1.34; 95% CI, 1.00-1.79; p=0.049; I² =41%), while no statistically significant difference was observed in the incidence of other adverse pregnancy outcomes. Conclusion: Thiopurines used in women with IBD during pregnancy is not associated with congenital malformations, LBW, SGA, or spontaneous abortion, but appears to have an association with an increased risk of preterm birth.