Use of macrolides during pregnancy and the risk of birth defects: a population-based study

Pharmacoepidemiol Drug Saf. 2015 Dec;24(12):1241-8. doi: 10.1002/pds.3900. Epub 2015 Oct 29.


Purpose: Macrolides have been linked to the occurrence of congenital heart defects, but findings are inconsistent. We therefore aimed to estimate the risk of major congenital malformations (MCMs) after fetal exposure to macrolides, focusing on cardiac malformations.

Methods: From the Quebec Pregnancy Cohort (1998-2008), women exposed to a macrolide or penicillin in the first trimester and unexposed women were studied. There were 135 859 pregnancies included; 914 were exposed to azithromycin, 734 to erythromycin, 686 to clarithromycin, and 9106 to penicillin during the first trimester. Cases of MCMs were identified within the first year of life.

Results: After adjusting for potential confounders, azithromycin (RR = 1.19, 95%CI: 0.98, 1.44; 120 exposed cases), erythromycin (RR = 0.96, 95%CI: 0.74, 1.24; 66 exposed cases) and clarithromycin use (RR = 1.12, 95%CI: 0.99, 1.42; 79 exposed cases) during the first trimester of pregnancy were not statistically significantly associated with the risk of MCMs; no associations were observed for cardiac malformations.

Conclusions: First trimester exposure to any of the macrolides was not associated with an increased risk of overall MCMs or cardiac malformations specifically.

Keywords: Quebec Pregnancy Cohort; azithromycin; cardiac malformations; erythromycin; macrolides; major malformations; pharmacoepidemiology; pregnancy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Bacterial Agents / adverse effects*
  • Azithromycin / adverse effects
  • Clarithromycin / adverse effects
  • Cohort Studies
  • Erythromycin / adverse effects
  • Female
  • Heart Defects, Congenital / chemically induced
  • Heart Defects, Congenital / epidemiology*
  • Humans
  • Infant, Newborn
  • Macrolides / adverse effects*
  • Penicillins / adverse effects
  • Pregnancy
  • Pregnancy Trimester, First
  • Prenatal Exposure Delayed Effects / epidemiology*
  • Prenatal Exposure Delayed Effects / etiology
  • Quebec / epidemiology
  • Registries
  • Risk Factors


  • Anti-Bacterial Agents
  • Macrolides
  • Penicillins
  • Erythromycin
  • Azithromycin
  • Clarithromycin