Is metronidazole safe during pregnancy?

Metronidazole Safety in Pregnancy

Metronidazole is safe to use during pregnancy after the first trimester, with oral metronidazole 250 mg three times daily for 7 days being the recommended regimen for the second and third trimesters, while topical metronidazole is safe throughout all trimesters due to minimal systemic absorption. 1, 2

First Trimester Considerations

• Oral metronidazole is contraindicated during the first trimester according to FDA labeling and ACOG guidance, despite meta-analyses showing no evidence of teratogenicity in humans 1, 3
• The FDA classifies metronidazole as pregnancy category B, meaning animal studies show no harm but adequate human studies are lacking 1
• For bacterial vaginosis in the first trimester, use clindamycin vaginal cream 2% instead (one full applicator intravaginally at bedtime for 7 days) 1
• Topical metronidazole (0.75-1%) is safe throughout all trimesters, including the first, due to significantly lower systemic absorption compared to oral administration 2, 4

Second and Third Trimester Use

• Oral metronidazole 250 mg three times daily for 7 days is the CDC-recommended regimen for bacterial vaginosis during the second and third trimesters 1
• Alternative regimens include metronidazole 2g orally as a single dose, or metronidazole gel 0.75% intravaginally 1
• Meta-analyses show no association between metronidazole exposure in later trimesters and preterm birth, low birth weight, or congenital anomalies 1
• For inflammatory bowel disease patients requiring treatment for perianal sepsis or pouchitis, metronidazole can be given throughout pregnancy 5

Evidence Quality and Nuances

The evidence base is robust but contains an important caveat:

• Multiple prospective studies and meta-analyses consistently demonstrate no teratogenic risk 6, 7
• One Israeli prospective cohort study of 228 women found no difference in major malformations (1.6% vs 1.4% in controls), though it noted reduced neonatal birth weight 7
• A 2021 review found metronidazole associated with 70% increased risk of spontaneous abortion, but this should be interpreted cautiously as the severity of genitourinary infection itself is a major confounder 8
• Historical studies from 1978 involving 597 pregnant women treated with metronidazole showed no effect on low birth weight, stillbirths, or congenital abnormalities 9

Clinical Pitfalls to Avoid

• Do not use metronidazole gel intravaginally during the first trimester - existing data do not support topical intravaginal use in early pregnancy 1
• Do not confuse clindamycin vaginal cream with clindamycin vaginal ovules, which are not recommended during pregnancy 1
• If using a single 2g oral dose during lactation, stop breastfeeding for 12-24 hours after the dose 2
• Long-term maternal therapy could theoretically risk neonatal bleeding by inhibiting vitamin K synthesis; treat mother and neonate with phytomenadione (vitamin K) if prolonged therapy is used 2

Rationale for Treatment Despite Concerns

Untreated bacterial vaginosis and trichomoniasis carry significant risks including premature rupture of membranes, chorioamnionitis, preterm labor, preterm birth, postpartum endometritis, and post-cesarean wound infection 1, 2

• Treatment of bacterial vaginosis in high-risk pregnant women may reduce the risk of preterm delivery 1, 2
• The benefits of treating these infections typically outweigh theoretical risks, particularly after the first trimester 6, 10

Route-Specific Safety Algorithm

For topical conditions (e.g., rosacea):

• Use topical metronidazole 0.75-1% throughout all trimesters - systemic absorption is minimal 2, 4

For systemic infections requiring oral therapy:

• First trimester: Avoid oral metronidazole; use alternative antibiotics 1, 3
• Second and third trimesters: Oral metronidazole 250 mg three times daily for 7 days is safe and recommended 1

For intravaginal infections:

• First trimester: Use clindamycin vaginal cream 2%, not metronidazole gel 1
• Second and third trimesters: Either metronidazole gel 0.75% or oral metronidazole are acceptable 1