Randomized controlled trial comparing 400μg sublingual misoprostol versus placebo for prevention of primary postpartum hemorrhage

Introduction: obstetric hemorrhage is estimated to cause 25% of all maternal deaths and is the leading direct cause of maternal mortality worldwide. The World Health Organization recommended the use of uterotonics that should be offered for all women who will give birth but in some countries or in special situations oxytocin is not available. The goal of this study is to determine whether the 400μg dose of Misoprostol decreases the incidence of postpartum hemorrhage (PPH) of women who did not show signs of hemorrhage.

Methods: a prospective randomized double blind controlled trial was conducted between February 2012 and June 2012, among women in the active stage of labor attending the Obstetric Gynecology Department, University Hospital Farhat Hached of Sousse, Tunisia. Women with term singleton pregnancies greater than 32 weeks of amenorrhea with anticipated vaginal delivery were eligible for the study. Participants were randomly assigned to receive 400 μg sublingual Misoprostol or 2 ets of placebo immediately after cord clamping. The primary outcome measures were an estimation of blood loss including the subjective finding of vaginal hemorrhage > 500 ml, the decrease of hemoglobin and hematocrit, a change in hemodynamic parameters, and the need for additional dose of oxytocin. Secondary outcomes were occurrence of possible side effects such as: headache, nausea, vomiting, pyrexia, diarrhea and abdominal pain.

Results: a total of 211 patients were randomized: 111 in the Misoprostol group (Cytotec*) and 100 patients in the placebo group. The two groups were similar in terms of sociodemographic characteristics. Significant difference between the 400-μg of Misoprostol and placebo group were recorded in mean postpartum blood and PPH occurrence. The difference in pre- and postpartum hemoglobin loss (expressed in grams per 100 ml) was 1.21 ± 1.05 for the Misoprostol group and 1.51 ± 0.74 for the placebo group with significant difference (p = 0.02). No differences were observed in the occurrence of headache, dizziness, vomiting, diarrhea and metallic taste but the incidence of shivering was more than twice as great among women receiving Misoprostol than among those treated with placebo with a significant difference (p = 0.01). Similarly, women who received Misoprostol had a significantly higher mean temperature after delivery in comparison with those receiving placebo.

Conclusion: misoprostol, administered as 400 μg after delivery, appears to be effective for the prevention of post-partum hemorrhage, but its side effects appears to be significant.

Keywords: Postpartum hemorrhage; maternal mortality; misoprostol; prevention; side effects; uterotonics.