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.