Metronidazole Safety in Pregnancy
Metronidazole can be safely used during pregnancy, particularly after the first trimester, with multiple studies and meta-analyses showing no consistent association with teratogenic or mutagenic effects in newborns. 1
Trimester-Specific Recommendations
First Trimester
- Avoid oral metronidazole during the first trimester when alternative treatments are available, though this is based on precautionary principles rather than definitive evidence of harm 2, 3
- Topical metronidazole (0.75-1%) is safe throughout all trimesters due to significantly lower systemic absorption compared to oral administration 3
- For bacterial vaginosis in first trimester, clindamycin vaginal cream 2% is the preferred first-line treatment (one full applicator intravaginally at bedtime for 7 days) 3
- For trichomoniasis, delay treatment until after the first trimester 2
Second and Third Trimesters
- Oral metronidazole is safe and recommended for appropriate indications 1
- Metronidazole 250 mg orally three times daily for 7 days is the recommended regimen for bacterial vaginosis in pregnancy 1, 3
- For trichomoniasis after first trimester, metronidazole 2g orally in a single dose is recommended 2
- Alternative regimen: metronidazole 500 mg twice daily for 7 days 1
Clinical Indications During Pregnancy
Bacterial Vaginosis
- All symptomatic pregnant women should be tested and treated 1
- BV is associated with premature rupture of membranes, chorioamnionitis, preterm labor, preterm birth, postpartum endometritis, and post-cesarean wound infection 1, 3
- High-risk pregnant women (those with previous preterm delivery) should be screened and treated at the first prenatal visit to potentially reduce preterm delivery 1
- Follow-up evaluation 1 month after treatment completion should be considered in high-risk women to evaluate treatment effectiveness 1
Inflammatory Bowel Disease
- Metronidazole can be given for pouchitis, perianal Crohn's disease, or intra-abdominal abscesses from fistulizing Crohn's disease 1
Evidence Quality and Safety Profile
Human Studies
- Multiple studies and meta-analyses have not demonstrated a consistent association between metronidazole use during pregnancy and teratogenic or mutagenic effects 1
- A prospective controlled cohort study of 228 women (86.2% with first-trimester exposure) found no difference in major malformation rates compared to controls (1.6% vs 1.4%, P=0.739) 4
- Review of nearly four decades of literature indicates metronidazole is not teratogenic regardless of trimester 5
FDA Classification
- Pregnancy Category B: Reproduction studies in rats at doses up to five times the human dose revealed no evidence of impaired fertility or harm to the fetus 6
- Metronidazole crosses the placental barrier and enters fetal circulation rapidly 6
Important Caveats
Dosing Considerations
- Lower doses are recommended during pregnancy to minimize fetal exposure 1, 2
- The 250 mg three times daily regimen is preferred over the 500 mg twice daily regimen used in non-pregnant women 1
Conflicting Animal Data
- Animal studies using extremely high and prolonged doses suggested possible mutagenicity, but this has not been demonstrated in humans 2
- Recent rat studies at 130 mg/kg showed placental changes and reduced fetal weight, but these doses far exceed human therapeutic doses 7, 8
- These animal findings should not alter clinical practice given the robust human safety data 5, 4
Treatment Benefits vs. Risks
- Untreated bacterial vaginosis and trichomoniasis are associated with preterm birth and low birth weight 5
- Treatment with metronidazole may decrease the incidence of preterm birth and complications from prematurity 5
- The benefits of treating symptomatic infections typically outweigh theoretical risks, especially after the first trimester 1