Progestogens for preterm birth prevention: A systematic review and meta-analysis by drug route

Purpose: Progestogen has been investigated as a preventive intervention among women with increased preterm birth risk. Our objective was to systematically review the effectiveness of intramuscular (IM), vaginal, and oral progestogens for preterm birth and neonatal death prevention. Methods: We included articles published from January 1966 to January 2013 and found 27 randomized trials with data for Bayesian meta-analysis. Results: Across all studies, only vaginal and oral routes were effective at reducing preterm births (IM risk ratio [RR] 0.95, 95 % Bayesian credible interval [BCI]: 0.88-1.03; vaginal RR 0.87, 95 % BCI: 0.80-0.94; oral RR 0.64, 95 % BCI: 0.49-0.85). However, when analyses were limited to only single births all routes were effective at reducing preterm birth (IM RR 0.77, 95 % BCI: 0.69-0.87; vaginal RR 0.80, 95 % BCI: 0.69-0.91; oral RR 0.66, 95 % BCI: 0.47-0.84). Only IM progestogen was effective at reducing neonatal deaths (IM RR 0.78, 95 % BCI: 0.56-0.99; vaginal RR 0.75, 95 % BCI: 0.45-1.09; oral RR 0.72, 95 % BCI: 0.09-1.74). Vaginal progestogen was effective in reducing neonatal deaths when limited to singletons births. Conclusions: All progestogen routes reduce preterm births but not neonatal deaths. Future studies are needed that directly compare progestogen delivery routes.