Oral Misoprostol in Preventing Postpartum Hemorrhage in Resource-Poor Communities: A Randomized Controlled Trial

Abstract

The commonest cause of maternal deaths worldwide is postpartum bleeding, and the great majority of such deaths take place in developing countries such as India where women frequently do not deliver their children in a hospital setting. The major cause is uterine atony, which can be prevented by administering a uterotonic agent such as oxytocin. Such treatment remains impractical for much of the developing world, where women giving birth are cared for by untrained attendants. In addition, injected uterotonic agents must be stored in the cold and require active management of the third stage of labor. Orally administered misoprostol, a prostaglandin E1 analogue, is a comparatively inexpensive alternative to oxytocin that has proved to be effective and safe, does not need to be refrigerated, and has a long shelf life. The investigators report a trial, conducted in rural India, which compared a single oral dose of 600 μg of misoprostol (n = 812) with placebo (n = 808) for preventing acute postpartum hemorrhage, defined as 500 mL or more within 2 hours after delivery. Medication was administered within 5 minutes of cutting the umbilical cord. The rate of acute severe bleeding (1000 mL or more within 2 hours) also was estimated. The actively treated women and placebo recipients were similar with respect to demographic, clinical, and perinatal features. The overall incidence of acute postpartum hemorrhage was 9.2%, occurring in 6.4% of misoprostol-treated women compared to 12% of placebo recipients, a highly significant difference (P < 0.0001). The relative risk for actively treated women compared with the placebo group was 0.53 (95% confidence interval, 0.39–0.74). All but 2 of 10 women with acute severe postpartum bleeding had received the placebo. Overall mean blood loss was lessened by misoprostol (214 versus 262 mL; P < 0.0001). Actively treated women were less likely to require transfer to a higher-level facility, blood transfusion, and surgical interventions. There were no group differences in delayed postpartum bleeding or infection. Rates of neonatal fever, vomiting, and diarrhea did not differ in the two groups. Oral administration of the prostaglandin analogue misoprostol is an effective, safe, inexpensive, and easily administered means of limiting the risk of postpartum bleeding in areas where medical resources may be scarce.