Impact of metronidazole therapy on preterm birth in women with bacterial vaginosis flora (Gardnerella vaginalis): a randomised, placebo controlled trial

OBJECTIVE: To ascertain whether metronidazole treatment of women with a heavy growth of Gardnerella vaginalis during mid-pregnancy would reduce the risk of spontaneous preterm birth. DESIGN: A multicentre, randomised, placebo-controlled trial. SETTING: Four metropolitan hospitals. PARTICIPANTS: Eight hundred and seventy-nine singleton women with a heavy growth of G. vaginalis or Gram stain indicative of bacterial vaginosis at 19 weeks of gestation. INTERVENTIONS: Oral metronidazole (400 mg) or placebo twice daily for two days at 24 weeks of gestation, and at 29 weeks if G. vaginalis found in test-of-cure swab four weeks after treatment. MAIN OUTCOME MEASURES: Spontaneous preterm birth less than 37 weeks. RESULTS: Intention-to-treat analysis showed no difference between metronidazole and placebo groups in overall preterm birth (31/429 7.2% vs 32/428 7.5%) or spontaneous preterm birth (20/429 4.7% vs 24/428 5.6%). Among the 480 women with bacterial vaginosis treatment had no effect on spontaneous preterm birth (11/242 4.5% vs 15/238 6.3%). In the subset of 46 women with a previous preterm birth, women in the metronidazole group showed a significant reduction in spontaneous preterm birth (2/22 9.1% vs 10/24 41.7%, OR 0.14, 95% CI 0.01-0.84). A treatment effect was also found in compliant women with a previous preterm birth and bacterial vaginosis (0/14 0% vs 6/17 35.3%, OR 0.0, 95% CI 0.0-0.94). CONCLUSION: Metronidazole treatment of women with a heavy growth of G. vaginalis or bacterial vaginosis did not reduce the preterm birth rate. Among women with a previous preterm birth, treatment reduced the risk of spontaneous preterm birth. Further studies are required to confirm these findings.