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Progestogens for Preterm Birth Prevention

A Systematic Review and Meta-Analysis

Likis, Frances E., DrPH, CNM; Edwards, Digna R. Velez, PhD; Andrews, Jeffrey C., MD; Woodworth, Alison L., PhD; Jerome, Rebecca N., MLIS, MPH; Fonnesbeck, Christopher J., PhD; McKoy, J. Nikki, MPH; Hartmann, Katherine E., MD, PhD

doi: 10.1097/AOG.0b013e3182699a15

OBJECTIVE: We systematically reviewed the effectiveness of progestogens for prevention of preterm birth among women with prior spontaneous preterm birth, multiple gestations, preterm labor, short cervix, or other indications.

DATA SOURCES: We searched MEDLINE and EMBASE databases for English language articles published from January 1966 to October 2011.

METHODS OF STUDY SELECTION: We excluded publications that were not randomized controlled trials or had fewer than 20 participants, identifying 34 publications, of which 19 contained data for Bayesian meta-analysis.

TABULATION, INTEGRATION, AND RESULTS: Two reviewers independently extracted data and assigned overall quality ratings based on predetermined criteria. Among women with prior preterm birth and a singleton pregnancy (five randomized controlled trials), progestogen treatment decreased the median risk of preterm birth by 22% (relative risk [RR] 0.78, 95% Bayesian credible interval 0.68–0.88) and neonatal death by 42% (RR 0.58, 95% Bayesian credible interval 0.27–0.98). The evidence suggests progestogen treatment does not prevent prematurity (RR 1.02, 95% Bayesian credible interval 0.87–1.17) or neonatal death (RR 1.44, 95% Bayesian credible interval 0.46–3.18) in multiple gestations. Limited evidence suggests progestogen treatment may prevent prematurity in women with preterm labor (RR 0.62, 95% Bayesian credible interval 0.47–0.79) and short cervix (RR 0.52, 95% Bayesian credible interval 0.36–0.70). Across indications, evidence about maternal, fetal, or neonatal health outcomes, other than reducing preterm birth and neonatal mortality, is inconsistent, insufficient, or absent.

CONCLUSION: Progestogens prevent preterm birth when used in singleton pregnancies for women with a prior preterm birth. In contrast, evidence suggests lack of effectiveness for multiple gestations. Evidence supporting all other uses is insufficient to guide clinical care. Overall, clinicians and patients lack longer-term information to understand whether intervention has the ultimately desired outcome of preventing morbidity and promoting normal childhood development.

Evidence supports progestogen use among women with prior preterm birth, demonstrates no benefit in multiple gestations, and is limited or insufficient for other indications.

From the Vanderbilt Evidence-based Practice Center and the Vanderbilt Epidemiology Center, Institute for Medicine and Public Health, and the Departments of Medicine, Obstetrics and Gynecology, Pathology, Microbiology, and Immunology, Biomedical Informatics, Knowledge Management, and Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee.

Supported in part by the Agency for Healthcare Research and Quality (contract number: 290-2007-10065-I).

The authors thank Dr. Melissa McPheeters for providing methods expertise, Ms. Tracy Shields for assisting with study selection and data extraction, and Mr. Jeffrey Seroogy for providing data coordination and editorial assistance.

Corresponding author: Frances E. Likis, DrPH, NP, CNM, Investigator, Vanderbilt Evidence-based Practice Center, Research Assistant Professor, Department of Medicine, Vanderbilt University, 2525 West End Avenue, 6th Floor, Nashville, TN 37203-1738; e-mail:

Financial Disclosure The authors did not report any potential conflicts of interest.

© 2012 by The American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.