Association of antibiotics therapy during pregnancy with spontaneous miscarriage: a systematic review and meta-analysis

Purpose: This systematic review and meta-analysis of observational studies were conducted to assess the association between antibiotics use during pregnancy and spontaneous miscarriage. Methods: A systematic search of online databases as well as reference lists of retrieved studies were performed up to September 2018 to identify observational studies that investigated the association between antibiotics use and spontaneous miscarriage. The retrieved studies were assessed for methodological quality. Pooled relative risk (RR) and 95% confidence intervals were calculated using DerSimonian and Laird method. Random-effects meta-analysis was used to account for conceptual heterogeneity. Sensitivity analysis was performed to assess the robustness of pooled estimates using Stata software. Results: Of 1435 retrieved studies, 89 were reviewed in depth and 12 (8 prospective cohort and 4 population-based case–control studies) met the criteria for inclusion in a systematic review with 1,084,792 participants and 7015 cases of spontaneous miscarriage. Finally, 11 studies were included in the meta-analysis (one study was not included in the meta-analysis owing to methodological issues and low-quality score). Overall percentage of miscarriage in women who received antibiotics was 2.6%. After adjusting for important potential confounders, use of macrolides (RR: 1.42; 95% CI 1.04, 1.93), quinolones (RR: 2.48; 95% CI 1.46, 4.20), and tetracyclines (RR: 2.57; 95% CI 1.95, 3.38) during pregnancy were significantly associated with spontaneous miscarriage. In macrolides class, a significant positive association was found between clarithromycin and spontaneous miscarriage (RR: 1.98; 95% CI 1.46, 2.70). Sensitivity analysis demonstrated the consistency of the results, indicating that the meta-analysis model was robust. Conclusion: Findings support a significant positive association between use of macrolides (especially clarithromycin), quinolones, and tetracyclines during pregnancy and spontaneous miscarriage, although it should be interpreted with caution in the context of limitations of the available data. Review registration: International register for systematic reviews; PROSPEROCRD42018093465.