Ciprofloxacin exposure and adverse pregnancy outcomes: A Danish nationwide cohort study.

OBJECTIVE: To examine the association between maternal exposure to ciprofloxacin and the risk of miscarriage and major malformations. DESIGN: A nationwide register-based cohort study. SETTING: Data were obtained from the Medical Birth Registry, the National Hospital Registry, the Danish National Prescription Registry and Statistics Denmark. POPULATION: Data were collected in the period between 1997 and 2016 and included all registered pregnancies that ended in an elective termination, miscarriage, stillbirth or a live birth. Exposure was defined as redeeming one or more prescriptions of ciprofloxacin. METHODS: Miscarriage was defined as a diagnosis given before 22 weeks without any medical intervention. Major malformations were classified according to EUROCAT 1.4. We matched ciprofloxacin-exposed pregnancies to unexposed pregnancies on the propensity score in a ratio 1:4. To estimate the hazard ratio (HR) of miscarriage a Cox proportional hazard regression model was used. A log binomial model was used to estimate the relative risk ratio (RR) of major malformations. MAIN OUTCOME MEASURES: HR of miscarriage and the RR of major malformations. RESULTS: A total of 1 650 649 pregnancies were identified. Of these, 10 250 (2050 ciprofloxacin-exposed) and 6100 (1220 ciprofloxacin-exposed) were included in the miscarriage and major malformation analysis, respectively. The HR of miscarriage was 0.99 (95% confidence interval [CI] 0.84-1.17). For major malformation, the RR was 1.01 (95% CI 0.72-1.40). For the organ-specific major malformations and the sensitivity analyses, no significant increased risks were identified. CONCLUSION: We demonstrated no association between miscarriage and maternal ciprofloxacin exposure within the first 22 weeks of pregnancy, or between major malformations and maternal exposure during the first trimester. TWEETABLE ABSTRACT: No association between maternal ciprofloxacin exposure and adverse pregnancy outcomes.