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Abstract
Background Literature surrounding the association between antidepressant use during pregnancy and miscarriage is conflicting. We aimed to conduct a systematic review and meta-analysis of studies among pregnant women regarding the association between exposure to antidepressants during pregnancy and the risk of miscarriage, compared with pregnant women not exposed to antidepressants.
Design We conducted a systematic review and meta-analysis of non-randomised studies.
Data sources We searched Medline, Embase and PsychINFO up to 6 August 2023.
Eligibility criteria and outcomes Case-control, cohort and cross-sectional study designs were selected if they compared individuals exposed to any antidepressant class during pregnancy to comparator groups of either no antidepressant use or an alternate antidepressant.
Data extraction and synthesis Effect estimates were extracted from selected studies and pooled using a random-effects meta-analysis. Risk of bias (RoB) was assessed using the Risk of Bias in Non-Randomised Studies of Interventions (ROBINS-I) tool, and heterogeneity assessed using the I2 statistic. Subgroup analyses were used to explore antidepressant classes and the impact of confounding by indication.
Results 1800 records were identified from the search, of which 29 were included in the systematic review and meta-analysis. The total sample included 5 671 135 individuals. Antidepressant users initially appeared to have a higher risk of miscarriage compared with unexposed individuals from the general population (summary effect estimate: 1.24, 95% CI 1.18 to 1.31, I2=69.2%; number of studies (n)=29). However, the summary estimate decreased when comparing against unexposed individuals with maternal depression (1.16, 1.04 to 1.31; I2=58.6%; n=6), suggesting confounding by indication may be driving the association. 22 studies suffered from serious RoB, and only two of the 29 studies were deemed at moderate RoB.
Conclusions After accounting for maternal depression, there is little evidence of any association between antidepressant use during pregnancy and miscarriage. Instead, the results indicate the biasing impact of confounding by indication.
- Depression & mood disorders
- EPIDEMIOLOGY
- Maternal medicine
Data availability statement
Data are available upon reasonable request. Please contact the first author (SS) if you would like to see any data not included in the article or supplementary material.
This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.
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Data availability statement
Data are available upon reasonable request. Please contact the first author (SS) if you would like to see any data not included in the article or supplementary material.
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Footnotes
SS and FM are joint first authors.
Contributors All authors helped with interpretation of results. SS did the full-text screening, data extraction, risk of bias assessment, statistical analysis and wrote the report. SS was responsible for the overall content as the guarantor. FM did the title and abstract screening, full-text screening, the second review of data extraction and risk of bias assessment, statistical analysis and had input on the report writing. HF did the title and abstract screening, full-text screening, and had input on all other elements of the paper. DR suggested the research question, provided supervision and comment on the manuscript.
Funding SS is supported by an NIHR predoctoral fellowship (NIHR301109). FM is supported by the Wellcome Trust (WT 218495/Z/19/Z). HF and DR acknowledge support from the NIH (1R01NS107607). This research was also supported by the NIHR Biomedical Research Centre at the University of Bristol and the University Hospitals Bristol and Weston NHS Foundation Trust.
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review Not commissioned; externally peer reviewed.
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