Is metronidazole (antibiotic) safe for pregnant women?

Metronidazole Safety in Pregnancy

Oral metronidazole tablets are safe to use during the second and third trimesters of pregnancy but should be avoided during the first trimester, while topical metronidazole formulations are safe throughout all trimesters due to minimal systemic absorption. 1, 2

First Trimester Considerations

• The FDA explicitly contraindicates oral metronidazole tablets during the first trimester of pregnancy for trichomoniasis treatment. 3
• The CDC and ACOG recommend avoiding oral metronidazole in the first trimester as a precautionary measure, though this is based on theoretical concerns rather than conclusive evidence of human teratogenicity. 1, 4
• Historical concerns stem from animal studies using extremely high doses (approximately 33 times the human dose), but these findings have not been replicated in human studies. 4, 3
• For bacterial vaginosis in the first trimester, clindamycin vaginal cream 2% is the preferred first-line treatment (one full applicator intravaginally at bedtime for 7 days). 1, 2
• Topical metronidazole (0.75-1%) remains safe throughout the first trimester due to significantly lower systemic absorption compared to oral formulations. 2

Second and Third Trimester Use

• Oral metronidazole becomes safe and is recommended during the second and third trimesters at a dose of 250 mg three times daily for 7 days for bacterial vaginosis. 1, 2
• Alternative regimens include metronidazole 2g orally as a single dose or metronidazole gel 0.75% intravaginally. 1
• The FDA classifies metronidazole as pregnancy category B, indicating no evidence of fetal harm in animal studies at standard doses. 1, 3
• Meta-analyses have shown no association between metronidazole exposure during later trimesters and preterm birth, low birth weight, or congenital anomalies. 5

Special Clinical Situations

Inflammatory Bowel Disease with Perianal Sepsis

• For pregnant women with Crohn's disease requiring antibiotic therapy for perianal sepsis, metronidazole and/or ciprofloxacin are recommended treatment options throughout pregnancy. 5
• In a small case series of women with IBD, neither metronidazole nor ciprofloxacin was associated with poor pregnancy outcomes. 5

Trichomoniasis Management

• For trichomoniasis diagnosed in the first trimester, treatment should be delayed until after the first trimester. 4
• After the first trimester, metronidazole 2g orally in a single dose is the recommended treatment. 4

Evidence Quality and Nuances

• The strongest human evidence contradicts teratogenicity concerns: A prospective controlled cohort study of 228 pregnant 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). 6
• A comprehensive literature review spanning nearly four decades concluded that metronidazole is not teratogenic regardless of trimester. 7
• One 2021 review noted a 70% increased risk of spontaneous abortion, but this should be interpreted cautiously as it may reflect the severity of underlying genitourinary infection rather than the medication itself. 8
• One animal study (2023) in rats showed maternal and fetal hepatotoxicity at 130 mg/kg body weight, but this dose is not comparable to standard human therapeutic doses and conflicts with decades of human safety data. 9

Important Clinical Pitfalls

• Do not confuse clindamycin vaginal cream with clindamycin vaginal ovules - the ovules are not recommended during pregnancy. 1
• Avoid clindamycin vaginal cream in later pregnancy as evidence from three trials shows increased adverse events (prematurity and neonatal infections) after use. 1
• Do not use metronidazole gel intravaginally during the first trimester - existing data do not support topical metronidazole agents during pregnancy for this indication. 1
• If prolonged maternal therapy is required, consider treating both mother and neonate with vitamin K (phytomenadione) due to theoretical risk of neonatal bleeding from vitamin K synthesis inhibition. 2

Rationale for Treatment

• Bacterial vaginosis is associated with serious adverse pregnancy outcomes including premature rupture of membranes, preterm labor, preterm birth, and postpartum endometritis. 1, 2
• Treatment of bacterial vaginosis in high-risk pregnant women may reduce the risk of preterm delivery, making the benefit-risk ratio favorable after the first trimester. 1, 2