Objective: To review the available evidence concerning the relationship between the exposure to metronidazole during pregnancy and the risk of preterm delivery and birth defects. Methods: Studies investigating the association between gestational use of oral metronidazole on human subjects and the risk of preterm birth or/and birth defects were systematically retrieved from MEDLINE and EMBASE databases. We selected studies published in English or French between 1964 and 2012. Where effect estimates were not reported, crude ORs along with 95% confidence intervals were calculated. Results: We selected 17 studies investigating the association between exposure to oral metronidazole and the risk of preterm birth, from which 12 were randomized clinical trials. In addition, we identified 13 studies devoted to the relationship between metronidazole and birth defects, from which 10 were cohort studies, 1 was a case-control study and 2 were meta-analysis. Conclusion: During pregnancy, treating bacterial vaginosis and trichomoniasis with metronidazole is effective and offers no teratogen risk. Benefit of metronidazole in the reduction of preterm birth was demonstrated for the combination of this medication with other antibiotics. Additional information is needed when metronidazole is used in association with other agents.
Keywords: Birth defects, metronidazole, pregnancy, preterm birth, systematic review.