In a randomized, controlled trial in rural India, women who took oral misoprostol after delivery were significantly less likely than those who took a placebo to develop acute or acute severe postpartum hemorrhage; in addition, their volume of postpartum blood loss was lower.1 Compared with women taking the placebo, those taking misoprostol had relative risks of 0.5 for acute and 0.2 for acute severe postpartum hemorrhage. Mean total blood loss was 214 ml in the misoprostol group and 262 ml in the placebo group.
Postpartum hemorrhage causes a third of the world's maternal deaths, and nearly all of these deaths occur in women who give birth at home or without a skilled attendant at delivery. In India, half of all births occur under these conditions; because the majority of Indian women are also anemic, they are at high risk for death from blood loss. Oxytocin, the drug most often used to prevent postpartum hemorrhage, cannot be used in much of India because it must be refrigerated and administered by trained medical personnel. Researchers conducted a large, randomized, placebo-controlled study to test the effectiveness of misoprostol, an inexpensive alternative, in preventing postpartum hemorrhage in rural communities where skilled medical care is unavailable. Misoprostol does not require refrigeration and can be taken orally.
The trial was conducted between September 2002 and December 2005 in Belgaum District of Karnataka State; the sample included more than 1,600 women drawn from 43 villages, in which more than half of deliveries occur at home or at village facilities with the help of auxiliary nurse midwives. Only women expecting an uncomplicated vaginal birth were eligible; reasons for exclusion included previous or planned cesarean birth, low hemoglobin levels, antepartum bleeding, hypertension and previous pregnancy complications. The remaining women were randomly assigned to receive either a single dose of 600 mcg of misoprostol (809) or a placebo (807) immediately after delivery.
Specially trained midwives administered the misoprostol and monitored participants for up to two hours, while measuring blood loss. Demographic, clinical and perinatal data were collected for both groups.
The mean age of all participants was 23, and the average time since their last pregnancy was 2.8 years. Twenty-nine percent had no other children, 60% had one or two other children, and 11% had three or more. Nearly two-thirds of the women were literate, and most reported having made three or more prenatal visits. Almost half gave birth at home; two in 10 had preterm deliveries, and one in 10 experienced perineal tears during delivery.
Acute postpartum hemorrhage (loss of at least 500 ml of blood within two hours of delivery) occurred in 6.4% of women who had taken misoprostol and 12.0% of those who had received the placebo; compared with the placebo group, the intervention group had a relative risk of 0.5. The proportions of women in the two groups who had acute severe postpartum hemorrhage (loss of at least 1,000 ml of blood) were also significantly different: 0.2% and 1.2%, respectively; compared with the placebo group, the misoprostol group had a relative risk of 0.2. Significant differences were also found for total blood loss over the two-hour period: Women who took misoprostol had a mean loss of 214 ml, whereas those who took the placebo lost an average of 262 ml. The difference between the two groups in blood loss for the second hour was even greater for the 41 women who continued to bleed (183 ml vs. 343 ml). Furthermore, compared with women who took the placebo, those who took misoprostol were significantly less likely to require transfer to a higher-level facility (0.5% vs. 1.5%), a blood transfusion (0.1% vs. 0.9%) or surgical intervention (0.1% vs. 1.0%). Transient shivering and fever were more common among women taking misoprostol than among those taking the placebo, but there were no differences in the proportions experiencing nausea, vomiting or diarrhea.
According to the researchers, the study had some limitations. The sample was restricted to low-risk women; thus, the findings are not generalizable to women with high-risk pregnancies. In addition, midwives recruited later in the study may have been more experienced, and patients admitted later may have benefited from the general improvement in midwife training and monitoring that occurred during the study period. Overall, the researchers say, this trial demonstrated that oral misoprostol is "safe, effective, and inexpensive ($1.00 per 600 mcg dose) for women giving birth in low-resource settings, and is currently the only available pharmacological option for preventing postpartum haemorrhage and reducing postpartum blood loss in these communities."—J. Thomas
1. Derman RJ et al., Oral misoprostol in preventing postpartum haemorrhage in resource-poor communities: a randomised controlled trial, Lancet, 2006, 368(9543):1248–1253