- First-trimester macrolide prescriptions are associated with increased risk for any major malformations (especially cardiovascular) in children.
- Risk for genital malformations (hypospadias) persists after first trimester.
Why this matters
- Prescribe macrolide alternatives whenever possible in pregnant women and use macrolides with caution.
- Of 104,605 children, 8.3% (8632) were born to mothers prescribed 1 macrolide prescription and 91.7% (95,973) to mothers prescribed 1 penicillin prescription during pregnancy.
- Negative controls:
- 82,314 children: mothers prescribed preconception macrolides (11,874) or penicillins (70,440).
- 53,735 study cohort siblings with prenatal macrolide (4512) or penicillin (49,223) exposure.
- Major malformations prevalence per 1000 live births:
- First-trimester macrolides: 27.65.
- Second/third-trimester macrolides: 19.5.
- First-trimester penicillin: 17.65.
- Second/third-trimester penicillin: 17.27.
- With first-trimester macrolides, adjusted risk ratios (aRRs; 95% CIs):
- Any malformation: 1.55 (1.19-2.03);
- Cardiovascular malformation: 1.62 (1.05-2.51).
- With macrolides in any trimester:
- Genital malformations: aRR, 1.58 (95% CI, 1.14-2.19).
- With erythromycin in first trimester:
- Any malformation: aRR, 1.50 (95% CI, 1.13-1.99).
- Retrospective, population-based cohort analysis evaluating association between macrolide antibiotics during pregnancy and risk for major malformations, neurodevelopmental disorders in their children.
- Funding: National Institute for Health Research.
- Bias toward the null, effect dilution.
- Inability to capture antibiotic dispensing/use.
- Outcomes misclassifications, birth bias.