The More, the Better? Combining Interventions to Prevent Preterm Birth in Women at Risk: a Systematic Review and Meta-Analysis

Objectives To systematically examine the evidence around the combination of interventions to prevent preterm birth. Methods Without language restrictions, we searched clinicaltrials.gov and five electronic databases (Medline, EMBASE, CINAHL, Cochrane CENTRAL, and Web of Science) up to July 7, 2016. We included randomized and non-randomized studies where asymptomatic women at risk of preterm birth received any combination of progesterone, cerclage, or pessary compared with either one or no intervention. Primary outcomes were preterm birth <34 and <37 weeks and neonatal death. Two independent reviewers extracted data using a piloted form and assessed risk and direction of bias. We pooled data with unlikely or unclear bias using random-effects meta-analyses. Comparisons with likely bias (e.g., confounding by indication) were not pooled. Results We screened 1335 results and assessed 154 full texts, including seven studies. In singletons, we found no differences in preterm birth <34 weeks when comparing pessary & progesterone with pessary alone (RR 1.30, 95% CI 0.70–2.42) or progesterone alone (RR 1.16, 95% CI 0.79–1.72). Similarly, we found no differences in preterm birth <37 weeks when comparing cerclage & progesterone with cerclage alone (RR 1.04, 95% CI 0.56–1.93) or with progesterone alone (RR 0.82, 95% CI 0.57–1.19) nor between pessary & progesterone and pessary alone (RR 1.04, 95% CI 0.62–1.74). No data were available for neonatal death in singletons. Conclusions Despite being a common clinical practice, evidence to support the combined use of multiple versus single interventions for preventing preterm birth is scarce.