Is metronidazole (antibiotic) safe to use during pregnancy?

Metronidazole Use During Pregnancy

Metronidazole is contraindicated during the first trimester of pregnancy, but can be safely used after the first trimester if clinically indicated. 1, 2

Safety Profile by Trimester

First Trimester

• Metronidazole is explicitly contraindicated during the first trimester of pregnancy according to FDA labeling and CDC guidelines 1, 3
• For bacterial vaginosis treatment during first trimester, clindamycin vaginal cream 2% is the preferred alternative treatment 4, 2
• For trichomoniasis, treatment should be delayed until after the first trimester whenever possible 2

Second and Third Trimesters

• Metronidazole can be safely used after the first trimester for appropriate indications 2, 4
• For trichomoniasis after first trimester, metronidazole 2g orally in a single dose is recommended 3, 2
• For bacterial vaginosis during second and third trimesters, oral metronidazole 250 mg three times daily for 7 days is a recommended option 4

Evidence on Safety

• The FDA classifies metronidazole as pregnancy category B, indicating no evidence of harm to the fetus in animal studies 1
• Prospective controlled cohort studies have confirmed that metronidazole does not represent a major teratogenic risk in humans when used in recommended doses 5
• A study of 597 pregnant women treated with metronidazole for trichomoniasis found no increased incidence of low birth weight, stillbirths, or congenital abnormalities compared to untreated women 6

Considerations for Use

• When treating pregnant women with metronidazole after the first trimester, lower doses are recommended to minimize fetal exposure 2
• Metronidazole crosses the placental barrier and enters fetal circulation rapidly 1
• Historical concerns about metronidazole stemmed from animal studies using extremely high doses that suggested possible mutagenicity, though this has not been demonstrated in humans 2

Important Cautions

• Some research suggests that metronidazole used alone during the second trimester may be associated with a higher rate of preterm delivery in high-risk populations 7
• A more recent study found metronidazole may be associated with increased risk of spontaneous abortion, though this should be interpreted cautiously due to potential confounding by the severity of genitourinary infection 8
• For high-risk pregnant women with bacterial vaginosis, treatment in the second trimester may help reduce risk of preterm delivery when used appropriately 2, 4

Treatment Failures

• If treatment failure occurs with standard regimens for trichomoniasis, retreatment with metronidazole 500 mg twice daily for 7 days is recommended (after first trimester) 3
• For repeated treatment failures, consultation with an infectious disease specialist is advised 3

Follow-Up Recommendations

• Follow-up visits are generally unnecessary if symptoms resolve 4
• For high-risk pregnant women, a follow-up evaluation one month after treatment completion may be considered 4

Remember that while metronidazole is contraindicated in the first trimester, the benefits of treatment after this period typically outweigh the risks when clinically indicated for conditions like bacterial vaginosis or trichomoniasis.