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Published on: August 4, 2021
Exposure to Systemic Antimicrobials During Pregnancy and Risk of Miscarriage: A Population-Based Registry Study
Thomas Boissiere-O'Neill1,2, Marleen M H J van Gelder2, Hilde M Engjom3
1Child Health Research Centre, The Children's Health and Environment Program, The University of Queensland, Brisbane, QLD, Australia.
Objective:
To estimate miscarriage risk following gestational antimicrobial exposure while addressing biases that have affected previous studies.
Design:
Population-based cohort study.
Setting:
Linkage of four nationwide registries: Medical Birth Registry of Norway (MBRN), Norwegian Prescribed Drug Registry (NorPD), Norwegian Patient Registry (NPR) and Norwegian Control and Payment of Health Reimbursements Database (KUHR).
Population Or Sample:
A total of 704 082 pregnancies (2009-2018), with 91 836 (13.0%) exposed to systemic antimicrobials in early pregnancy.
Methods:
Time-stratified Cox regression models with overlap weights were used, considering time-varying exposures and a 14-day lag to prevent reverse causation. Elective terminations were right-censored to address competing risks, with adjustment for common infections and probabilistic bias analysis for confounding by indication.
Main Outcome Measures:
Miscarriage and gestational age at miscarriage, captured from NPR, KUHR and MBRN, using the UiO pregnancy algorithm.
Results:
Nitrofurantoin, pivmecillinam and amoxicillin were not associated with increased miscarriage risk. Metronidazole (HR = 2.00; 95% CI: 1.82-2.21), ciprofloxacin (HR = 1.89; 95% CI: 1.62-2.20), cephalexin (HR = 1.87; 95% CI: 1.57-2.22), fluconazole (HR = 1.61; 95% CI: 1.45-1.78), trimethoprim-sulfas (HR = 1.49; 95% CI: 1.36-1.63) and others showed associations with miscarriage. Probabilistic bias analysis indicated that associations for common antimicrobials may be driven by the underlying infections.
Conclusions:
Nitrofurantoin, pivmecillinam and amoxicillin did not increase miscarriage risk, but other less commonly used antimicrobials may carry higher risks. By addressing key biases, this study provided a more reliable assessment of miscarriage risks associated with antimicrobial use in early pregnancy.
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