307: Preterm Birth Prevention in Twin Pregnancies with Progesterone, Pessary or Cerclage, a Meta-Analysis

We aimed to determine the effectiveness of progesterone (natural and 17-alpha-hydroxyprogesterone caproate, 17-OHPC), cerclage and pessary for prevention of preterm birth (PTB) in twin pregnancies. We systematically searched Medline, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, and ISI Web of Science, without language restrictions, from their inceptions until January 25, 2016. We included randomized controlled trials of progesterone, cerclage or pessary for the prevention of PTB in women with a twin pregnancy and without symptoms of threatened preterm labor. Study quality was appraised with the Cochrane Risk of Bias tool and standard pairwise inverse variance random effects meta-analyses were performed using Review Manager. We included 24 trials involving 6,627 women with twin pregnancies. In separate pairwise meta-analyses, none of the interventions overall significantly reduced the risk of PTB <34 weeks, <37 weeks or neonatal death compared to control. In the subgroup of women receiving natural progesterone, the relative risk (RR) of PTB <34 weeks was 0.80 (95% CI 0.63-1.01), with significant decreases in some key secondary outcomes including very low birth weight, VLBW <1500 g (RR 0.67, 95% CI 0.51-0.89), respiratory distress syndrome (RDS, RR 0.79, 95% CI 0.64-0.98), mechanical ventilation (RR 0.60, 95% CI 0.48-0.75) and in a single study, early neonatal death (RR 0.49, 95% CI 0.33-0.73). In contrast, 17-OHPC significantly increased the risk of PTB (<34 weeks: RR 1.56, 95% CI 1.07-2.28; <37 weeks: RR 1.13, 95% CI 1.02-1.24), and other key secondary outcomes including VLBW (RR 1.46, 95% CI 1.18-1.82), RDS (RR 1.37, 95% CI 1.12-1.67) and neonatal intensive care unit admission (RR 1.35, 95% CI 1.13-1.60). In women with a short cervix, natural progesterone decreased some secondary outcomes such as VLBW (RR 0.45, 95% CI 0.32-0.63), mechanical ventilation (RR 0.47, 95% CI 0.32-0.69) and in a single study, early neonatal death (RR 0.49, 95% CI 0.33-0.73). In this first overarching meta-analysis of prevention of PTB in twin gestations, natural progesterone improves some PTB related outcomes in women overall and in women with a short cervix, while 17-OHPC is clearly harmful. No benefit or harm was observed in women with twin pregnancies receiving cerclage or pessary.