Sublingual misoprostol is inferior to intramuscular oxytocin for the prevention of postpartum hemorrhage (PPH) in women undergoing uncomplicated birth at a regional hospital in Uganda, according to trial results published in PLOS Medicine. The randomized non-inferiority trial, conducted by Esther Cathyln Atukunda at the Mbarara University of Science and Technology, Uganda, and colleagues, showed that PPH incidence in the misoprostol arm exceeded that in the oxytocin arm by 11.2% (95% confidence interval 6.44%-16.1%).
PPH is responsible for 25-30% of maternal deaths. This complication can be prevented either with an intramuscular injection of oxytocin, which is stored cold, or a sublingual dose of misoprostol, which is stable at room temperature. To determine if misoprostol should be substituted where oxytocin is impractical, the researchers measured blood loss over the first 24 post-partum hours in 1140 women treated with either oxytocin or misoprostol (along with a placebo mimicking the alternate treatment, and double-blinded). PPH (loss of >500mL blood) occurred in 28.6% and 17.4% of the women in the misoprostol and oxytocin arms, respectively (p<0.001). Severe PPH (loss of >1000mL blood) occurred in 3.6% and 2.7% of participants in the misoprostol and oxytocin groups, respectively (p=0.391). On average, women given misoprostol lost slightly more blood by 2 hours (341.5 ml versus 304.2 ml; p=0.002) and 24 hours (484.7 ml versus 432.8 ml; p<0.001) than those given oxytocin. There were no significant differences in deaths, transfusions, or the use of additional drugs, but women given misoprostol experienced shivering (p<0.001) and fever (p=0.005) more often than those given oxytocin.
Study limitations include possible selection bias due to a high rate of eligible participants declining participation (54.9%), and inapplicability to women at high risk of birth complications, who were excluded. The authors state: “These data demonstrate that, in settings where it is available, oxytocin should remain a preferred agent for prevention of PPH. However, sublingual misoprostol appears to maintain an important role for prevention of severe PPH and other complications of PPH where oxytocin is not available.”
Sublingual Misoprostol versus Intramuscular Oxytocin for Prevention of Postpartum Hemorrhage in Uganda: A Double-Blind Randomized Non-Inferiority Trial Atukunda EC, Siedner MJ, Obua C, Mugyenyi GR, Twagirumukiza M, et al., PLoS Med, doi:10.1371/journal.pmed.1001752, published 4 November 2014.
Funding for this study was provided by the Father Bash Foundation and Divine Mercy Hospital scholarship awards to ECA (FBF PS1981). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
ECA, CO, MT, and AA previously worked with an independent EU-funded project aimed at documenting access to medicines in Africa and South Asia (AMASA) from where the gaps and research questions for this study were identified.