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BACKGROUND Prostaglandins have mainly been used for postpartum haemorrhage 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 trials register (March 2003). SELECTION CRITERIA Randomized or quasi-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. There were no language preferences. DATA COLLECTION AND ANALYSIS Eligibility, trial quality and data extraction were done by two reviewers independently. MAIN RESULTS Twenty-four misoprostol and eight intramuscular prostaglandin trials (34,203 participants) were included. The data comparing oral misoprostol to no uterotonics/placebo are from five trials and difficult to interpret because of the heterogeneity between trials. However, the data do not suggest a substantive reduction in the rate of postpartum haemorrhage or other measures of blood loss. Oral misoprostol 600 mcg shows clinically and statistically significantly more blood loss = 1000 ml compared with conventional injectable uterotonics (seven trials, 22,749 women, 3.6% versus 2.7%; relative risk (RR) 1.34, 95% confidence interval (CI) 1.16 to 1.55). Shivering and elevated body temperature (> 38 masculine C) are the main side-effects of misoprostol and are dose related (600 mcg versus 400 mcg: shivering - two trials, RR: 1.33; 95% CI: 1.07 to 1.64). Compared to oxytocin the RR of any shivering with 600 mcg oral misoprostol is 3.29 (seven trials, 22746 women; 19.7% versus 6.0%, 95% CI 3.03 to 3.56) and temperature greater than 38 masculine C is RR 6.78 (seven trials, 22,09 women; 6.3% versus, 95% CI 5.55 to 8.30). Injectable prostaglandins are associated with reduced mean blood loss in the third stage of labour (weighted mean difference -70 ml, 95% CI -73 to -67 ml) when compared to conventional injectable uterotonics but have more side-effects. There are scarce data from this comparison on severe postpartum haemorrhage and the use of additional uterotonics, the primary outcomes of this review. REVIEWER'S CONCLUSIONS Neither intramuscular prostaglandins nor misoprostol are preferable to conventional injectable uterotonics as part of the active management of the third stage of labour especially for low-risk women. Future research on prostaglandin use after birth should focus on the treatment of postpartum haemorrhage rather than prevention where they seem to be more promising.