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.