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.