Effectiveness of progesterone, cerclage and pessary for preventing preterm birth in singleton pregnancies: a systematic review and network meta-analysis.

BACKGROUND: Preterm birth (PTB) is the leading cause of infant death, but it is unclear which intervention is best to prevent it. OBJECTIVES: To compare progesterone, cerclage and pessary, determine their relative effects and rank them. SEARCH STRATEGY: We searched Medline, EMBASE, CINAHL, Cochrane CENTRAL and Web of Science (to April 2016), without restrictions, and screened references of previous reviews. SELECTION CRITERIA: We included randomised trials of progesterone, cerclage or pessary for preventing PTB in women with singleton pregnancies at risk as defined by each study. DATA COLLECTION AND ANALYSIS: We extracted data by duplicate using a piloted form and performed Bayesian random-effects network meta-analyses and pairwise meta-analyses. We rated evidence quality using GRADE, ranked interventions using SUCRA and calculated numbers needed to treat (NNT). MAIN RESULTS: We included 36 trials (9425 women; 25 low risk of bias trials). Progesterone ranked first or second for most outcomes, reducing PTB < 34 weeks [odds ratio (OR) 0.44; 95% credible interval (CrI) 0.22-0.79; NNT 9; low quality], <37 weeks (OR 0.58; 95% CrI 0.41-0.79; NNT 9; moderate quality), and neonatal death (OR 0.50; 95% CrI 0.28-0.85; NNT 35; high quality), compared with control, in women overall at risk. We found similar results in the subgroup with previous PTB, but only a reduction of PTB < 34 weeks in women with a short cervix. Pessary showed inconsistent benefit and cerclage did not reduce PTB < 37 or <34 weeks. CONCLUSIONS: Progesterone was the best intervention for preventing PTB in singleton pregnancies at risk, reducing PTB < 34 weeks, <37 weeks, neonatal demise and other sequelae. TWEETABLE ABSTRACT: Progesterone was better than cerclage and pessary to prevent preterm birth, neonatal death and more in network meta-analysis.

Preterm birth prevention in twin pregnancies with progesterone, pessary, or cerclage: a systematic review and meta-analysis.

BACKGROUND: About half of twin pregnancies deliver preterm, and it is unclear whether any intervention reduces this risk. OBJECTIVES: To assess the evidence for the effectiveness of progesterone, cerclage, and pessary in twin pregnancies. SEARCH STRATEGY: We searched Medline, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, and ISI Web of Science, without language restrictions, up to 25 January 2016. SELECTION CRITERIA: Randomised controlled trials of progesterone, cerclage, or pessary for preventing preterm birth in women with twin pregnancies, without symptoms of threatened preterm labour. DATA COLLECTION AND ANALYSIS: Two independent reviewers extracted data using a piloted form. Study quality was appraised with the Cochrane Risk of Bias tool. We performed pairwise inverse variance random-effects meta-analyses. MAIN RESULTS: We included 23 trials (all but three were considered to have a low risk of bias) comprising 6626 women with twin pregnancies. None of the interventions significantly reduced the risk of preterm birth overall at <34 or <37 weeks of gestation, or neonatal death, our primary outcomes, compared to a control group. In women receiving vaginal progesterone, the relative risk (RR) of preterm birth <34 weeks of gestation was 0.82 (95% CI 0.64-1.05, seven studies, I2  36%), with a significant reduction in some key secondary outcomes, including very low birthweight (<1500 g, RR 0.71, 95% CI 0.52-0.98, four studies, I2  46%) and mechanical ventilation (RR 0.61, 95% CI 0.45-0.82, four studies, I2  22%). CONCLUSION: In twin gestations, although no overarching intervention was beneficial for the prevention of preterm birth and its sequelae, vaginal progesterone improved some important secondary outcomes. TWEETABLE ABSTRACT: Vaginal progesterone may be beneficial in twin pregnancies, but not 17-OHPC, cerclage, or pessary.