Clarithromycin Use in the First Trimester Is Not Associated With Fetal Abnormalities

Clarithromycin is a macrolide antibiotic that is widely used, including during pregnancy. However, few studies have examined the safety of clarithromycin alone in early pregnancy. In this two-center retrospective cohort study, we evaluated pregnancy outcomes following first-trimester clarithromycin exposure. Information on medication use and obstetric history was obtained retrospectively. Pregnancy outcomes were collected using patient-completed postal questionnaires. We investigated pregnancy outcomes and the incidence of major anomalies in women who took clarithromycin during the first trimester, and compared them with those in women who took β-lactams or control drugs known to be safe during pregnancy. The primary outcome was the incidence of major anomalies, and the secondary outcome was overall pregnancy outcomes. The numbers of major anomalies in the clarithromycin group (n = 347), β-lactam group (n = 1367), and control group (n = 1313) were 8 (2.31%), 26 (1.90%), and 18 (1.37%), respectively. When restricted to patients with live births only, the numbers of major anomalies in these groups (n = 333, n = 1323, and n = 1261, respectively) were 8 (2.40%), 25 (1.89%), and 18 (1.43%), respectively, with no significant differences between groups. The odds ratio for major anomalies in the clarithromycin group relative to the control group was 1.70 (95% confidence interval [CI], 0.73-3.94), while that relative to the β-lactam group was 1.28 (95% CI, 0.57-2.86). Inverse probability weighting to compensate for small sample sizes also yielded no significant differences. Overall, clarithromycin use during the first trimester was not associated with an increased risk of major anomalies relative to β-lactams or control drugs.