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

Mark A. Klebanoff; Ewoud Schuit; Ronald F. Lamont; Per Göran Larsson; Hein J. Odendaal; Austin Ugwumadu; Herbert Kiss; Ljubomir Petricevic; William W. Andrews; Matthew K. Hoffman; Andrew Shennan; Paul T. Seed; Robert L. Goldenberg; Lynda M. Emel; Vinay Bhandaru; Steven Weiner; Michael D. Larsen

doi:10.1111/ppe.12947

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

Mark A. Klebanoff^*, Ewoud Schuit, Ronald F. Lamont, Per Göran Larsson, Hein J. Odendaal, Austin Ugwumadu, Herbert Kiss, Ljubomir Petricevic, William W. Andrews, Matthew K. Hoffman, Andrew Shennan, Paul T. Seed, Robert L. Goldenberg, Lynda M. Emel, Vinay Bhandaru, Steven Weiner, Michael D. Larsen

^*Corresponding author for this work

Women & Children's Health

Research output: Contribution to journal › Review article › peer-review

1 Citation (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	239-251
Number of pages	13
Journal	Paediatric and Perinatal Epidemiology
Volume	37
Issue number	3
DOIs	https://doi.org/10.1111/ppe.12947
Publication status	Published - Mar 2023

Keywords

bacterial vaginosis
clindamycin
individual participant data
meta-analysis
metronidazole
preterm delivery
systematic review

Access to Document

10.1111/ppe.12947

Cite this

Klebanoff, M. A., Schuit, E., Lamont, R. F., Larsson, P. G., Odendaal, H. J., Ugwumadu, A., Kiss, H., Petricevic, L., Andrews, W. W., Hoffman, M. K., Shennan, A., Seed, P. T., Goldenberg, R. L., Emel, L. M., Bhandaru, V., Weiner, S., & Larsen, M. D. (2023). Antibiotic treatment of bacterial vaginosis to prevent preterm delivery: Systematic review and individual participant data meta-analysis. Paediatric and Perinatal Epidemiology, 37(3), 239-251. https://doi.org/10.1111/ppe.12947

@article{cc1a4cbaef3f47adbaa658fe611cac9c,

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

abstract = "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.",

keywords = "bacterial vaginosis, clindamycin, individual participant data, meta-analysis, metronidazole, preterm delivery, systematic review",

author = "Klebanoff, {Mark A.} and Ewoud Schuit and Lamont, {Ronald F.} and Larsson, {Per G{\"o}ran} and Odendaal, {Hein J.} and Austin Ugwumadu and Herbert Kiss and Ljubomir Petricevic and Andrews, {William W.} and Hoffman, {Matthew K.} and Andrew Shennan and Seed, {Paul T.} and Goldenberg, {Robert L.} and Emel, {Lynda M.} and Vinay Bhandaru and Steven Weiner and Larsen, {Michael D.}",

note = "Funding Information: Supported by Grant 5R21HD078877 from the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. P-G Larsson reports receiving financial support as a scientific advisor for Dynamic Code, which developed a molecular test for bacterial vaginosis. Funding Information: Supported by Grant 5R21HD078877 from the National Institutes of Health, National Institute of Child Health and Human Development. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. P‐G Larsson reports receiving financial support as a scientific advisor for Dynamic Code, which developed a molecular test for bacterial vaginosis. Eunice Kennedy Shriver Publisher Copyright: {\textcopyright} 2023 The Authors. Paediatric and Perinatal Epidemiology published by John Wiley & Sons Ltd.",

year = "2023",

month = mar,

doi = "10.1111/ppe.12947",

language = "English",

volume = "37",

pages = "239--251",

journal = "Paediatric and Perinatal Epidemiology",

issn = "0269-5022",

publisher = "Wiley-Blackwell",

number = "3",

}

Klebanoff, MA, Schuit, E, Lamont, RF, Larsson, PG, Odendaal, HJ, Ugwumadu, A, Kiss, H, Petricevic, L, Andrews, WW, Hoffman, MK, Shennan, A , Seed, PT, Goldenberg, RL, Emel, LM, Bhandaru, V, Weiner, S & Larsen, MD 2023, 'Antibiotic treatment of bacterial vaginosis to prevent preterm delivery: Systematic review and individual participant data meta-analysis', Paediatric and Perinatal Epidemiology, vol. 37, no. 3, pp. 239-251. https://doi.org/10.1111/ppe.12947

TY - JOUR

T1 - Antibiotic treatment of bacterial vaginosis to prevent preterm delivery

T2 - Systematic review and individual participant data meta-analysis

AU - Klebanoff, Mark A.

AU - Schuit, Ewoud

AU - Lamont, Ronald F.

AU - Larsson, Per Göran

AU - Odendaal, Hein J.

AU - Ugwumadu, Austin

AU - Kiss, Herbert

AU - Petricevic, Ljubomir

AU - Andrews, William W.

AU - Hoffman, Matthew K.

AU - Shennan, Andrew

AU - Seed, Paul T.

AU - Goldenberg, Robert L.

AU - Emel, Lynda M.

AU - Bhandaru, Vinay

AU - Weiner, Steven

AU - Larsen, Michael D.

N1 - Funding Information: Supported by Grant 5R21HD078877 from the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. P-G Larsson reports receiving financial support as a scientific advisor for Dynamic Code, which developed a molecular test for bacterial vaginosis. Funding Information: Supported by Grant 5R21HD078877 from the National Institutes of Health, National Institute of Child Health and Human Development. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. P‐G Larsson reports receiving financial support as a scientific advisor for Dynamic Code, which developed a molecular test for bacterial vaginosis. Eunice Kennedy Shriver Publisher Copyright: © 2023 The Authors. Paediatric and Perinatal Epidemiology published by John Wiley & Sons Ltd.

PY - 2023/3

Y1 - 2023/3

N2 - 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.

AB - 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.

KW - bacterial vaginosis

KW - clindamycin

KW - individual participant data

KW - meta-analysis

KW - metronidazole

KW - preterm delivery

KW - systematic review

UR - http://www.scopus.com/inward/record.url?scp=85146451338&partnerID=8YFLogxK

U2 - 10.1111/ppe.12947

DO - 10.1111/ppe.12947

M3 - Review article

C2 - 36651636

AN - SCOPUS:85146451338

SN - 0269-5022

VL - 37

SP - 239

EP - 251

JO - Paediatric and Perinatal Epidemiology

JF - Paediatric and Perinatal Epidemiology

IS - 3

ER -

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

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this