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

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Abstract

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.

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Acknowledgements

The present study was part of a thesis research conducted by Iran University of Medical Sciences (IUMS), Tehran, Iran. Authors would like to thank Dr. Nazemzadeh for improving the use of English in the manuscript and Ms. Roya Vesal Azad as a librarian for her assistance in systematic searching of the databases.

Funding

The authors received no specific funding for this work.

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Authors and Affiliations

  1. Department of Gynecology and Obstetrics, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

    Ara Omranipoor & Maryam Kashanian

  2. Department of Epidemiology, School of Public Health, Iran University of Medical Sciences, P.O. Box: 22431993, Tehran, Iran

    Mohsen Dehghani

  3. Department of Epidemiology, Faculty of Health, Mashhad University of Medical Sciences, Mashhad, Iran

    Masoumeh Sadeghi

  4. Endocrinology Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran

    Hamid Reza Baradaran

  5. Ageing Clinical and Experimental Research Team, Institute of Applied Health Sciences, University of Aberdeen, Aberdeen, Scotland, UK

    Hamid Reza Baradaran

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  1. Ara Omranipoor
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Contributions

HRB and AO conceived the idea and designed the study. AO and MD collected data and reviewed the literature. MS and MD extracted data and appraised the studies. HRB and MD participated in data analysis, interpreted the results, and drafted the manuscript. AO and MK conceived the study aims and design and provided the data and measures. MS reanalyzed the data. MK, AO, HRB, and MS made substantial contribution to data interpretation, critical revision of the manuscript for important intellectual content, and final approval of the version to be submitted. All authors reviewed, discussed, provided critical comments, approved the final manuscript, and accepted responsibility for publication. The corresponding author had full access to all the data in the study.

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Correspondence to Mohsen Dehghani.

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Omranipoor, A., Kashanian, M., Dehghani, M. et al. Association of antibiotics therapy during pregnancy with spontaneous miscarriage: a systematic review and meta-analysis. Arch Gynecol Obstet 302, 5–22 (2020). https://doi.org/10.1007/s00404-020-05569-4

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