Antibiotic treatment of bacterial vaginosis to prevent preterm delivery: Systematic review and individual participant data meta-analysis

BackgroundBacterial vaginosis (BV) increases preterm delivery (PTD) risk, but treatment trials showed mixed results in preventing PTD. ObjectivesDetermine, using individual participant data (IPD), whether BV treatment during pregnancy reduced PTD or prolonged time-to-delivery. Data SourcesCochrane Systematic Review (2013), MEDLINE, EMBASE, journal searches, and searches (January 2013-September 2022) (bacterial vaginosis AND pregnancy) of (i) ; (ii) Cochrane Central Register of Controlled Trials; (iii) World Health Organization International Clinical Trials Registry Platform Portal; and (iv) Web of Science (bacterial vaginosis). Study Selection and Data ExtractionStudies randomising asymptomatic pregnant individuals with BV to antibiotics or control, measuring delivery gestation. Extraction was from original data files. Bias risk was assessed using the Cochrane tool. Analysis used one-step logistic and Cox random effect models, adjusting gestation at randomisation and PTD history; heterogeneity by I-2. Subgroup analysis tested interactions with treatment. In sensitivity analyses, studies not providing IPD were incorporated by multiple random-donor hot-deck imputation, using IPD studies as donors. ResultsThere were 121 references (96 studies) with 23 eligible trials (11,979 participants); 13 studies (6915 participants) provided IPD; 12 (6115) were incorporated. Results from 9 (4887 participants) not providing IPD were imputed. Odds ratios for PTD for metronidazole and clindamycin versus placebo were 1.00 (95% CI 0.84, 1.17), I-2 = 62%, and 0.59 (95% CI 0.42, 0.82), I-2 = 0 before; and 0.95 (95% CI 0.81, 1.11), I-2 = 59%, and 0.90 (95% CI: 0.72, 1.12), I-2 = 0, after imputation. Time-to-delivery did not differ from null with either treatment. Including imputed IPD, there was no evidence that either drug was more effective when administered earlier, or among those with a PTD history. ConclusionsClindamycin, but not metronidazole, was beneficial in studies providing IPD, but after imputing data from missing IPD studies, treatment of BV during pregnancy did not reduce PTD, nor prolong pregnancy, in any subgroup or when started earlier in gestation.

Automated summary

Using individual participant data (IPD), this study investigated whether treatment of bacterial vaginosis (BV) during pregnancy reduced the risk of preterm delivery (PTD). The results showed that clindamycin treatment was beneficial in studies providing IPD, but when data from studies without IPD were imputed, neither metronidazole nor clindamycin treatment reduced the risk of PTD or prolonged pregnancy. The timing of treatment and history of PTD did not affect treatment efficacy.