Metronidazole Safety in Pregnancy
Metronidazole is safe to use after the first trimester of pregnancy (second and third trimesters), but should be avoided during the first trimester when safer alternatives like clindamycin vaginal cream are available. 1, 2
First Trimester: Avoid Oral Metronidazole
The FDA drug label explicitly contraindicates metronidazole tablets during the first trimester of pregnancy for trichomoniasis treatment. 3
The Centers for Disease Control and Prevention (CDC) and American College of Obstetricians and Gynecologists (ACOG) recommend avoiding oral metronidazole in the first trimester due to precautionary concerns, although meta-analyses do not demonstrate teratogenicity in humans. 1, 2
For bacterial vaginosis in the first trimester, clindamycin vaginal cream 2% (one full applicator intravaginally at bedtime for 7 days) is the recommended first-line treatment. 1
Topical metronidazole (0.75-1% gel) is considered safe throughout all trimesters due to significantly lower systemic absorption compared to oral formulations, though intravaginal metronidazole gel is not recommended during the first trimester. 2
Second and Third Trimesters: Safe to Use
The CDC recommends oral metronidazole 250 mg three times daily for 7 days as a treatment option for bacterial vaginosis during the second and third trimesters. 1, 2
Alternative regimens include metronidazole 500 mg twice daily for 7 days or a single 2g oral dose. 2
Meta-analyses show no association between metronidazole exposure during later trimesters and preterm birth, low birth weight, or congenital anomalies. 1
The European Respiratory Society/Thoracic Society of Australia and New Zealand guidelines classify metronidazole as "possibly safe" during pregnancy when no safer alternatives exist, noting that most reports in humans found no association with increased risk of structural defects to the fetus. 4
FDA Classification and Animal Studies
The FDA classifies metronidazole as pregnancy category B, indicating no evidence of harm to the fetus in animal reproduction studies at doses up to five times the human dose, though adequate human studies are lacking. 1, 3
The FDA label notes that metronidazole crosses the placental barrier and enters fetal circulation rapidly, and because it is a carcinogen in rodents, it should be used during pregnancy only if clearly needed. 3
Historical concerns stemmed from animal studies using extremely high and prolonged doses that suggested possible mutagenicity, though this has not been demonstrated in humans. 5
Clinical Indications and Benefits
Bacterial vaginosis is associated with serious adverse pregnancy outcomes 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
All symptomatic pregnant women should be tested and treated for bacterial vaginosis to prevent these complications. 2
For inflammatory bowel disease, metronidazole can be given throughout pregnancy for pouchitis, perianal Crohn's disease, or intra-abdominal abscesses from fistulizing Crohn's disease. 2
Important Clinical Caveats
Lower doses are recommended during pregnancy to minimize fetal exposure. 2
Long-term maternal therapy could theoretically risk neonatal bleeding by inhibiting vitamin K synthesis; if prolonged therapy is used, treat both mother and neonate with phytomenadione (vitamin K). 4, 2
If a single 2g oral dose is used during lactation, stop breastfeeding for 12-24 hours after the dose. 4, 2
One older study (2007) suggested that second-trimester metronidazole used alone was linked with a greater risk of preterm delivery in high-risk populations, though this contradicts more recent meta-analyses and current CDC guidelines that support its safety. 6
A 2023 animal study in rats showed potential maternal and fetal hepatotoxicity and teratogenicity at 130 mg/kg body weight, but this dose is approximately 17 times higher than typical human doses and does not reflect clinical use. 7
Multiple prospective human studies confirm that metronidazole does not represent a major teratogenic risk when used in recommended doses. 8, 9