Antibiotic treatment of bacterial vaginosis to prevent preterm delivery: Systematic review and individual participant data meta‐analysis
Background Bacterial vaginosis (BV) increases preterm delivery (PTD) risk, but treatment trials showed mixed results in preventing PTD. Objectives Determine, using individual participant data (IPD), whether BV treatment during pregnancy reduced PTD or prolonged time‐to‐delivery. Data Sources Cochran...
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Published in | Paediatric and perinatal epidemiology Vol. 37; no. 3; pp. 239 - 251 |
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Main Authors | , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
England
Wiley Subscription Services, Inc
01.03.2023
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Subjects | |
Online Access | Get full text |
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Summary: | Background
Bacterial vaginosis (BV) increases preterm delivery (PTD) risk, but treatment trials showed mixed results in preventing PTD.
Objectives
Determine, using individual participant data (IPD), whether BV treatment during pregnancy reduced PTD or prolonged time‐to‐delivery.
Data Sources
Cochrane Systematic Review (2013), MEDLINE, EMBASE, journal searches, and searches (January 2013–September 2022) (“bacterial vaginosis AND pregnancy”) of (i) clinicaltrials.gov; (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 Extraction
Studies 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 I2. 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.
Results
There 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), I2 = 62%, and 0.59 (95% CI 0.42, 0.82), I2 = 0 before; and 0.95 (95% CI 0.81, 1.11), I2 = 59%, and 0.90 (95% CI: 0.72, 1.12), I2 = 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.
Conclusions
Clindamycin, 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. |
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Bibliography: | In addition, on behalf of the Protocol registered on PROSPERO CRD42015020304, May 6, 2015 Eunice Kennedy Shriver Tweetable Abstract NICHD Maternal‐Fetal Medicine Units Network In a meta‐analysis of bacterial vaginosis treatment in pregnancy and preterm delivery (PTD), we used individual participant data (IPD), imputing nonresponding studies. With only IPD clindamycin showed benefit to reduce PTD. Incorporating imputed studies we found no benefit of treatment, cumulatively or in any subgroup. A commentary based on this artlcle appears on pages 252‐253 Dr. Larsen and Mr. Weiner had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Klebanoff, Weiner, Schuit and Larsen involved in concept and design. Klebanoff, Schuit, Lamont, Larsson, Odendaal, Ugwumadu, Kiss, Petricevic, Andrews, Hoffman, Shennan, Seed, Goldenberg, Emel, Bhandaru, Weiner and Larsen involved in the acquisition, analysis or interpretation of the data. Klebanoff and Larsen involved in drafting the manuscript. Schuit, Lamont, Larsson, Odendaal, Ugwumadu, Kiss, Petricevic, Andrews, Hoffman, Shennan, Seed, Goldenberg, Emel, Bhandaru and Weiner involved in the critical revision of the manuscript for important intellectual content; Larsen, Weiner and Bhandaru involved in statistical analysis. AUTHOR CONTRIBUTIONS |
ISSN: | 0269-5022 1365-3016 1365-3016 |
DOI: | 10.1111/ppe.12947 |