A randomised placebo controlled trial of oral misoprostol in the third stage of labour

Br J Obstet Gynaecol. 1998 Sep;105(9):971-5. doi: 10.1111/j.1471-0528.1998.tb10259.x.


Objective: To compare oral misoprostol 400 microg with placebo in the routine management of the third stage of labour.

Design: A double-blind placebo controlled trial. Setting The labour ward of an academic hospital in Johannesburg, South Africa with 7000 deliveries per annum.

Participants: Low-risk women expected to deliver vaginally.

Methods: Women in labour were randomly allocated to receive either misoprostol 400 microg orally or placebo after the birth. Conventional oxytocics were given immediately if blood loss was thought to be more than usual. Postpartum blood loss in the first hour was measured by collection in a special flat plastic bedpan. Side effects were recorded.

Main outcome measures: Measured blood loss > or = 1000 ml within the first hour after birth. Use of additional oxytocics.

Results: The groups were well matched. Measured blood loss > or = 1000 ml occurred in 15/250 (6%) after misoprostol and 23/250 (9%) after placebo (relative risk 0.65; 95% confidence interval 0.35-1.22). The difference may have been reduced by the greater use of conventional oxytocics in the placebo group, which was statistically significant for intravenous oxytocin infusion (2.8% vs 8.4%, relative risk 0.33, 95% confidence interval 0.14-0.77). Shivering was more common in the misoprostol group (19% vs 5%, relative risk 3.69; 95% confidence interval 2.05-6.64).

Conclusions: Shivering has been shown in this study to be a specific side effect of misoprostol administered orally in the puerperium. No serious side effects were noted. Misoprostol shows promise as a method of preventing postpartum haemorrhage. Because of the potential benefits for childbearing women, particularly those in developing countries, further research to determine its effects with greater certainty should be expedited.

PIP: A randomized, double-blind study conducted at a teaching hospital in Johannesburg, South Africa, assessed oral misoprostol administration in the third stage of labor as a method of preventing postpartum hemorrhage. Women expected to deliver vaginally were randomly allocated to receive either 400 mcg of oral misoprostol (n = 250) or placebo (n = 250) immediately after delivery. Oxytocics were given if blood loss was perceived to be excessive. Blood loss of 1000 ml or above occurred in 15 women (6%) in the misoprostol group and in 23 controls (9%) (relative risk, 0.65; 95% confidence interval, 0.35-1.22; p = 0.18). The failure of this difference to attain statistical significance may reflect the greater rate of oxytocic use in the placebo group (8.4%) than in the misoprostol group (2.8%). Shivering was more common in the misoprostol group (19%) than the placebo group (5%). There were no other side effects. The potential of misoprostol to prevent postpartum hemorrhage merits further investigation, especially in developing countries where such an intervention could reduce maternal mortality and morbidity.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Double-Blind Method
  • Female
  • Humans
  • Labor Stage, Third
  • Misoprostol / administration & dosage*
  • Misoprostol / adverse effects
  • Oxytocics / administration & dosage*
  • Oxytocics / adverse effects
  • Postnatal Care / methods
  • Postpartum Hemorrhage / prevention & control*
  • Pregnancy


  • Oxytocics
  • Misoprostol