BACKGROUND AND PURPOSE:

• Macrolide antibiotics include erythromycin, clarithromycin, and azithromycin
• Studies have provided conflicting results
• Andersson et al. (BMJ, 2021) assessed the association between the use of macrolide antibiotics in pregnancy and the risk of major birth defects

METHODS:

• Nationwide, register based cohort study (1997 to 2016)
• Participants
  • Pregnancies ending with live birth
• Exposures
  • Macrolide use during first trimester (start of pregnancy through 12 weeks), compared with
    • Penicillin use during pregnancy | Matched 1:1
    • Recent macrolide use (six months to one month before becoming pregnant) | Matched 1:1
    • No antibiotics (from one month before or in the first trimester of pregnancy): Matched 1:4
• Primary outcome
  • Any major birth defect
  • Subgroups of birth defects

RESULTS:

• 1,192,539 live birth pregnancies
  • Macrolide use during pregnancy: 13,019 pregnancies
• Infants born with major birth defects
  • Macrolide use during pregnancy: 35.1 per 1000 pregnancies
  • Penicillin use during pregnancy: 37.0 per 1000 pregnancies
  • RR 0.95 (95% CI, 0.84 to 1.08)
  • Absolute risk difference −1.8 per 1000 pregnancies (95% CI, −6.4 to 2.7)
• Similar to penicillin use, there was no increased risk when comparing macrolide use during pregnancy vs
  • Recent macrolide use but not during pregnancy
    • RR 1.00 (95% CI, 0.88 to 1.14)
    • Absolute risk difference −0.1 per 100 pregnancies (95% CI, −4.8 to 4.7)
  • No antibiotic use
    • RR 1.05 (95% CI, 0.95 to 1.17)
    • Absolute risk difference 1.8 per 1000 pregnancies (95% CI, −1.7 to 5.3)
• Birth defect subgroup analysis
  • No increased risk with macrolide use in pregnancy was identified for specific birth defects
• No differences were found when analyses were performed for the individual macrolides
• Second and third trimester exposures (post hoc analyses)
  • No association with increased risk for major birth defects
  • RR 1.02 (95% CI, 0.93 to 1.12)

CONCLUSION:

• In this Danish cohort, there was no association between macrolide use during pregnancy and increased risk of congenital birth defects 
• The authors conclude

In contrast with a recent cohort study from the UK, we found no significantly increased risk of any of the 12 organ specific subgroups of birth defects, including defects of the heart, and no evidence of significant associations for individual macrolides

Learn More – Primary Sources:

Association between use of macrolides in pregnancy and risk of major birth defects: nationwide, register based cohort study

Related ObG Topics:

Is Macrolide Antibiotic Use During Pregnancy Linked to Increased Risk of Congenital Malformations?

Does Antibiotic Use Increase Risk of Spontaneous Abortion?

Do Common Antibiotics Increase Risk of Congenital Malformations?

Is Antibiotic Exposure in Pregnancy or Childhood Linked with Childhood Obesity?