Abstract
BACKGROUND: Many reproductive-aged North Americans use antibiotics in the weeks preceding conception or during early pregnancy. Antibiotic use may influence risk of spontaneous abortion (SAB) by disrupting the reproductive tract microbiome or treating harmful infections. However, this association has not been extensively studied. OBJECTIVE: To determine the extent to which periconceptional antibiotic use is associated with the risk of SAB. METHODS: We analysed data from an internet-based preconception cohort study of pregnancy planners. Eligible participants self-identified as female, were aged 21-45 years, resided in the USA or Canada, and conceived during 12 months of follow-up (n = 7890). Participants completed an enrolment questionnaire during June 2013-September 2021 and bimonthly follow-up questionnaires for up to 12 months or until a reported pregnancy, whichever came first. Pregnant participants completed questionnaires in early (~8-9 weeks) and late (~32 weeks) gestation. We assessed antibiotic use, including type (penicillins, nitrofurantoin, cephalosporins and macrolides) and indication for use, during the previous 4 weeks on preconception questionnaires. Participants reported pregnancies and SAB on follow-up and pregnancy questionnaires. We used Cox proportional hazards regression models with gestational weeks as the time scale to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between periconceptional antibiotic use and SAB, controlling for potential demographic, medical, and lifestyle confounders. RESULTS: Nineteen percent (n = 1537) of pregnancies ended in SAB. Participants reported periconceptional antibiotic use in 8% of pregnancies ending in SAB and 7% not ending in SAB. Periconceptional antibiotic use was not appreciably associated with SAB (adjusted HR 1.06, 95% CI 0.88, 1.28). We observed no strong associations between antibiotic type, indication for use, or recency of exposure and SAB risk. CONCLUSIONS: Periconceptional antibiotic use was not appreciably associated with SAB in this study. This association is likely complicated by antibiotic type and dosage, timing of conception, and the individual's overall health.