WHO multicentre randomised trial of misoprostol in the management of the third stage of labour

Background Postpartum haemorrhage is a leading cause of maternal morbidity and mortality. Active management of the third stage of labour, including us e of a uterotonic agent, has been shown to reduce blood loss. Misoprostol ( a prostaglandin Ell. analogue) has been suggested for this purpose because it has strong uterotonic effects, can be given orally, is inexpensive, and does not need refrigeration for storage. We did a multicentre, double-blind , randomised controlled trial to determine whether oral misoprostol is as e ffective as oxytocin during the third stage of labour. Methods In hospitals in Argentina, China, Egypt, Ireland, Nigeria, South Af rica, Switzerland, Thailand, and Vietnam, we randomly assigned women about to deliver vaginally to receive 600 mug misoprostol orally or 10 IU oxytoci n intravenously or intramuscularly, according to routine practice, plus cor responding identical placebos. The medications were administered immediatel y after delivery as part of the active management of the third stage of lab our. The primary outcomes were measured postpartum blood loss of 1000 mL or more, and the use of additional uterotonics without an unacceptable level of side-effects. We chose an upper limit of a 35% increase in the risk of b lood loss of 1000 mL or more as the margin of clinical equivalence, which w as assessed by the confidence interval of the relative risk. Analysis was b y intention to treat. Findings 9264 women were assigned misoprostol and 9266 oxytocin. 37 women i n the misoprostol group and 34 in the oxytocin group had emergency caesarea n sections and were excluded. 366 (4%) of women on misoprostol, had a measu red blood loss of 1000 mL or more, compared with 263 (3%) of those on oxyto cin (relative risk 1.39 [95% CI 1.19-1.63], p<0.0001). 1398 (15%) women in the misoprostol group and 1002 (11%) in the oxytocin group required additio nal uterotonics (1.40 [1.29-1.51], p<0.0001). Misoprostol use was also asso ciated with a significantly higher incidence of shivering (3.48 [3.15-3.84] ) and raised body temperature (7.17 [5.67-9.07]) in the first hour after de livery. Interpretation 10 IU oxytocin (intravenous or intramuscular) is preferable to 600 mug oral misoprostol in the active management of the third stage of labour in hospital settings where active management is the norm.