A M Gülmezoglu1, F Forna, J Villar, G J Hofmeyr. 1. Research Training in Human Reproduction (HRP), UNDP/UNFPA/WHO/World Bank Special Programme of Research, Development andDepartment of Reproductive Health and Research, World Health Organization, Geneva 27, Switzerland, 1211. gulmezoglum@who.int
Abstract
BACKGROUND: Prostaglandins have mainly been used for postpartum haemorrhage (PPH) when other measures fail. Misoprostol, a new and inexpensive prostaglandin E1 analogue, has been suggested as an alternative for routine management of the third stage of labour. OBJECTIVES: To assess the effects of prophylactic prostaglandin use in the third stage of labour. SEARCH STRATEGY: The Cochrane Pregnancy and Childbirth Group's Trials Register (February 2007) and PubMed (July 2006). SELECTION CRITERIA: Randomized trials comparing a prostaglandin agent with another uterotonic or no prophylactic uterotonic (nothing or placebo) as part of management of the third stage of labour. The primary outcomes were blood loss 1000 ml or more and the use of additional uterotonics. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed eligibility and trial quality and extracted data. MAIN RESULTS: Thirty-seven misoprostol and nine intramuscular prostaglandin trials (42,621 women) were included. Oral (seven trials, 2849 women) or sublingual misoprostol (relative risk (RR) 0.66; 95% confidence interval (CI) 0.45 to 0.98; one trial, 661 women) compared to placebo may be effective in reducing severe PPH and blood transfusion (RR 0.31; 95% CI 0.10 to 0.94; five oral misoprostol trials, 3519 women). The severe PPH analysis of oral misoprostol trials was not totalled due to significant heterogeneity. Compared to conventional injectable uterotonics, oral misoprostol was associated with higher risk of severe PPH (RR 1.32; 95% CI 1.16 to 1.51; 16 trials, 29,042 women) and use of additional uterotonics but with fewer blood transfusions (RR 0.81; 95% CI 0.64 to 1.02; 15 trials, 27,858 women). Additional uterotonic data were not totalled due to heterogeneity. Misoprostol use is associated with significant increases in shivering and a temperature of 38 degrees Celsius. There are scarce data comparing injectable prostaglandins with the conventional injectable uterotonics on severe PPH and the use of additional uterotonics, the primary outcomes of this review. AUTHORS' CONCLUSIONS: Misoprostol orally or sublingually at a dose of 600 mcg shows promising results when compared to placebo in reducing blood loss after delivery. The margin of benefit may be affected by whether other components of management of the third stage of labour are used or not. As side-effects are dose-related, research should be directed towards establishing the lowest effective dose for routine use, and the optimal route of administration. Neither intramuscular prostaglandins nor misoprostol are preferable to conventional injectable uterotonics as part of the management of the third stage of labour especially for low-risk women.
BACKGROUND:Prostaglandins have mainly been used for postpartum haemorrhage (PPH) when other measures fail. Misoprostol, a new and inexpensive prostaglandin E1 analogue, has been suggested as an alternative for routine management of the third stage of labour. OBJECTIVES: To assess the effects of prophylactic prostaglandin use in the third stage of labour. SEARCH STRATEGY: The Cochrane Pregnancy and Childbirth Group's Trials Register (February 2007) and PubMed (July 2006). SELECTION CRITERIA: Randomized trials comparing a prostaglandin agent with another uterotonic or no prophylactic uterotonic (nothing or placebo) as part of management of the third stage of labour. The primary outcomes were blood loss 1000 ml or more and the use of additional uterotonics. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed eligibility and trial quality and extracted data. MAIN RESULTS: Thirty-seven misoprostol and nine intramuscular prostaglandin trials (42,621 women) were included. Oral (seven trials, 2849 women) or sublingual misoprostol (relative risk (RR) 0.66; 95% confidence interval (CI) 0.45 to 0.98; one trial, 661 women) compared to placebo may be effective in reducing severe PPH and blood transfusion (RR 0.31; 95% CI 0.10 to 0.94; five oral misoprostol trials, 3519 women). The severe PPH analysis of oral misoprostol trials was not totalled due to significant heterogeneity. Compared to conventional injectable uterotonics, oral misoprostol was associated with higher risk of severe PPH (RR 1.32; 95% CI 1.16 to 1.51; 16 trials, 29,042 women) and use of additional uterotonics but with fewer blood transfusions (RR 0.81; 95% CI 0.64 to 1.02; 15 trials, 27,858 women). Additional uterotonic data were not totalled due to heterogeneity. Misoprostol use is associated with significant increases in shivering and a temperature of 38 degrees Celsius. There are scarce data comparing injectable prostaglandins with the conventional injectable uterotonics on severe PPH and the use of additional uterotonics, the primary outcomes of this review. AUTHORS' CONCLUSIONS:Misoprostol orally or sublingually at a dose of 600 mcg shows promising results when compared to placebo in reducing blood loss after delivery. The margin of benefit may be affected by whether other components of management of the third stage of labour are used or not. As side-effects are dose-related, research should be directed towards establishing the lowest effective dose for routine use, and the optimal route of administration. Neither intramuscular prostaglandins nor misoprostol are preferable to conventional injectable uterotonics as part of the management of the third stage of labour especially for low-risk women.