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Systematic Review of Randomized Controlled Trials of Misoprostol to Prevent Postpartum Hemorrhage

Villar, J. MD; Gülmezoglu, A. M. MD; Hofmeyr, G. Justus MD; Forna, F. MD


OBJECTIVE To assess the effects of prophylactic misoprostol use in the third stage of labor compared with injectable uterotonics or placebo or no treatment.

DATA SOURCES The Cochrane Pregnancy and Childbirth Group trials register; the Cochrane Library, including databases such as the database of systematic reviews and the Cochrane Controlled Trials Register; and MEDLINE were searched. Researchers in the field were also contacted. The date of the latest search was March 1, 2002.

METHODS OF STUDY SELECTION Randomized trials comparing misoprostol with injectable oxytocin or oxytocinergot preparations to prevent postpartum hemorrhage or placebo/no treatment as active management of the third stage of labor were eligible for inclusion. Eligibility and trial quality were assessed following selected criteria. Data were extracted and analyzed using RevMan software.

TABULATION, INTEGRATION, AND RESULTS Sixteen randomized trials with a total of 28,138 women were considered. Data were available for 27,498 women. Oral misoprostol (600 μg) is less effective than injectable uterotonics in reducing blood loss at least 1000 mL (relative risk [RR] 1.36, 95% confidence interval [CI] 1.17, 1.58) and increases the use of additional uterotonics. Shivering and pyrexia (temperature greater than 38C) are the main side effects of misoprostol and are dose related. Compared with injectable uterotonics, the RR of “any shivering” with misoprostol (600 μg) is 3.27 (95% CI 3.01, 3.56) and pyrexia is 6.96 (95% CI 5.65, 8.57). The RR of blood loss of 500 mL or more is 1.11 (95% CI 0.87, 1.43) and the RR of use of additional uterotonics is 1.80 (1.13, 2.85) in the three trials (1441 women) comparing rectal misoprostol (400 μg) with injectable uterotonics.

CONCLUSION Injectable oxytocin or oxytocinergot preparations are more effective than misoprostol as part of the active management of the third stage of labor.

Conventional injectable uterotonics are more effective than misoprostol in the active management of the third stage of labor.

United Nations Development Programme/United Nations Population Fund/World Health Organization/World Bank Special Programme of Research, Development and Research Training in Human Reproduction, World Health Organization, Geneva, Switzerland; Effective Care Research Unit, University of the Witwatersrand, Johannesburg/East London Hospital Complex, Johannesburg, South Africa; and Department of Obstetrics and Gynecology, Emory University School of Medicine, Atlanta, Georgia.

Address reprint requests to: A. Metin Gülmezoglu, MD, UNDP/UNFPA/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction, Department of Reproductive Health and Research, World Health Organization, 1211 Geneva 27, Switzerland; E-mail:

This review is based on “Prostaglandins for prevention of postpartum hemorrhage (Cochrane Review)” (Cochrane Database Syst Rev 2002; 3:CD000494).

Potential conflict of interest: JV, AMG, and GJH participated in the World Health Organization 1999 and 2001 trials, and GJH in the South African trials.

Dr. Gilda Piaggio provided useful comments to an earlier version of the manuscript.

Received February 12, 2002. Received in revised form May 10, 2002. Accepted June 12, 2002.

© 2002 by The American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.