Association of Quinolone Exposure in the First‐Trimester of Pregnancy and the Risk of Major Congenital Malformations: A Health Administrative Database Study in Japan

Purpose To evaluate the risk of major congenital malformations (MCMs) associated with quinolone exposure during the first trimester of pregnancy using a large administrative database in Japan. Methods A large claims database was used from January 2005 to November 2019. The dates of pregnancy onset and delivery were estimated using the developed algorithm. MCMs were defined according to the International Classification of Diseases, 10th revision codes. The risk of MCM associated with first‐trimester quinolone prescriptions was evaluated in women with infectious diseases diagnosed during the first trimester of pregnancy. We evaluated the overall risk of MCMs in infants, and odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by comparing women with first‐trimester prescriptions of quinolones with those without antibiotic prescriptions, adjusting for covariates with propensity score overlap weights. Results The prevalence of first‐trimester infectious diseases was 51.6% (47 121/91390). Among 47 121 women diagnosed with infectious diseases, 1 320 were prescribed quinolones during their first trimester of pregnancy. The overall prevalence of MCMs was 6.0% (2282/37766) in women unexposed to antibiotics and 5.9% (78/1320) in those exposed to quinolones. The first‐trimester prescription of quinolone was not significantly associated with the overall MCM prevalence when overlap‐weighted ORs (wOR) were calculated using propensity score overlap weights for covariates (wOR 0.904, 95% CIs 0.684–1.196). Conclusions Prescription of quinolones in the first‐trimester of pregnancy was not associated with an increased risk of MCMs in infants. Our findings may support clinical decision‐making when considering quinolone use during the first‐trimester of pregnancy.