A systematic review and meta-analysis of randomized controlled trials comparing 17-alpha-hydroxyprogesterone caproate versus placebo for the prevention of recurrent preterm birth.

BACKGROUND: Preterm birth causes an increased risk for perinatal morbidity and mortality.

OBJECTIVE: To determine whether mid-trimester 17-alpha-hydroxyprogesterone caproate (17-OHPC) reduces the risk of recurrent preterm birth and adverse perinatal outcomes.

SEARCH STRATEGY: Systematic search to identify relevant studies published in different languages, registered after 2000, using appropriate MeSH terms.

SELECTION CRITERIA: Inclusion criteria were women between 16 and 26+6  weeks of pregnancy with history of preterm delivery in any pregnancy randomized to either 17-OHPC or placebo/no treatment.

DATA COLLECTION AND ANALYSIS: The number of preterm births and adverse outcomes in the 17-OHPC and placebo arms over the total number of patients in each randomized group were used to calculate the risk ratio (RR) by random-effects models using the Mantel-Haenszel method. Between-study heterogeneity was assessed using tau2 , χ2 (Cochrane Q), and I2 statistics.

MAIN RESULTS: Four studies were included. There was a 29% (RR 0.71; 95% CI, 0.53-0.96; P=0.001), 26% (RR 0.74; 95% CI, 0.58-0.96; P=0.021), and 40% (RR 0.60; 95% CI, 0.42-0.85; P=0.004) reduction in recurrent preterm birth at <37, <35, and <32 weeks, respectively, in the 17-OHPC group compared with placebo. The reduction in neonatal death was 68% (RR 0.32; 95% CI, 0.15-0.66; P=0.002).

CONCLUSIONS: 17-OHPC could reduce the risk of recurrent preterm birth at <37, <35, and <28 weeks and neonatal death.

PROSPERO: CDR42017082190.