Supplementary Material for: Interventions for the Prevention of Preterm Premature Rupture of Membranes: a Systematic Review and Meta-Analysis

ABSTRACT Introduction: Preterm prelabour rupture of membranes (PPRoM) is a significant cause of maternal and perinatal morbidity and mortality. The aim of this project was to identify interventions that reduce the prevalence of PPRoM. Methods: Search strategy included a systematic literature search of MEDLINE, EMBASE, PubMed and Cochrane Library. The selection criteria included randomised control studies that compared a therapy to standard care (no therapy or placebo) in pregnancy and included PPRoM as an outcome. Risk of bias was assessed according to the Cochrane risk-of-bias tool for randomised trials. Odds ratios with 95% confidence intervals were calculated using random effects models. Quality of evidence was assessed using the GRADE methodology. Results: Twenty-nine studies examining 10 interventions met the inclusion criteria. Therapies included docosahexaenoic acid (DHA), aspirin, rofecoxib, vitamin C alone and with vitamin E, folic acid (alone, with iron, with iron and zinc, within a multiple micronutrient supplement), zinc, calcium, copper and treatment of bacterial vaginosis. There was no significant difference in the prevalence of PPRoM in the treatment groups compared to placebo, except for rofecoxib which showed an increased risk of PPRoM (RR 2.46, 95% CI 1.28 – 4.73; p = 0.007, 1 trial, 98 women; very low quality of evidence) and a multiple micronutrient supplement which showed a reduction in PPRoM (RR 0.40, 95% CI 0.19 – 0.84; p = 0.01, 1 trial, 1671 women; very low quality of evidence). Conclusions: No interventions have been convincingly shown to reduce the prevalence of PPRoM. Given this is a common problem leading to significant morbidity and mortality, further research is required.