Are Macrolide Antibiotics Safe During the First Trimester?

摘要

Malformations occurred more frequently among children whose mothers received a macrolide antibiotic such as erythromycin during early pregnancy. Antibiotics are often administered during pregnancy, and disentangling their effects from those of infection on the fetus is difficult. To clarify the effects of macrolide antibiotics administered during gestational weeks 4 to 13 (when organogenesis occurs), investigators queried a large U.K. database including 100,000 pregnancies between 1990 and 2016. Women who received macrolides (erythromycin, azithromycin, or clarithromycin) were compared with those who received a penicillin antibiotic. Among children whose mothers received first-trimester macrolides, incidence of major malformations was higher than among those whose mothers who received a penicillin antibiotic (28 vs. 18 per 1000 person-years; adjusted risk ratio, 1.5). Specifically, risk was increased for cardiovascular malformations (aRR, 1.6) and nervous system malformations (aRR, 2.3) although the latter were rare and the risk estimate was not statistically significant. Risk for genital malformations was significantly increased among children born to women exposed to macrolides during the second and third trimesters. Excess risks were robust to adjustment for potential confounders and comparison with women who received macrolides prior to pregnancy.