Misoprostol to prevent and treat postpartum haemorrhage: a systematic review and meta-analysis of maternal deaths and dose-related effects
G Justus Hofmeyr, A Metin Gülmezoglu, Natalia Novikova, Verena Linder, Sandra Ferreira & Gilda Piaggio
To review maternal deaths and the dose-related effects of misoprostol on blood loss and pyrexia in randomized trials of misoprostol use for the prevention or treatment of postpartum haemorrhage.
We searched the Cochrane Controlled Trials Register and Pubmed, without language restrictions, for “(misoprostol AND postpartum) OR (misoprostol AND haemorrhage) OR (misoprostol AND hemorrhage)”, and we evaluated reports identified through the Cochrane Pregnancy and Childbirth Group search strategy. Randomized trials comparing misoprostol with either placebo or another uterotonic to prevent or treat postpartum haemorrhage were checked for eligibility. Data were extracted, tabulated and analysed with Reviewer Manager (RevMan) 4.3 software.
We included 46 trials with more than 40 000 participants in the final analysis. Of 11 deaths reported in 5 trials, 8 occurred in women receiving ≥ 600 µg of misoprostol (Peto odds ratio, OR: 2.49; 95% confidence interval, CI: 0.76–8.13). Severe morbidity, defined as the need for major surgery, admission to intensive care, organ failure or body temperature ≥ 40 °C, was relatively infrequent. In prevention trials, severe morbidity was experienced by 16 of 10 281 women on misoprostol and by 16 of 10 292 women on conventional uterotonics; in treatment trials, it was experienced by 1 of 32 women on misoprostol and by 1 of 32 women on conventional uterotonics. Misoprostol recipients experienced more adverse events than placebo recipients: 8 of 2070 versus 5 of 2032, respectively, in prevention trials, and 5 of 196 versus 2 of 202, respectively, in treatment trials. Meta-analysis of direct and adjusted indirect comparisons of the results of randomized trials showed no evidence that 600 µg are more effective than 400 µg for preventing blood loss ≥ 1000 ml (relative risk, RR: 1.02; 95% CI: 0.71–1.48). Pyrexia was more than twice as common among women who received ≥□600 µg rather than 400 µg of misoprostol (RR: 2.53; 95% CI: 1.78–3.60).
Further research is needed to more accurately assess the potential beneficial and harmful effects of misoprostol and to determine the smallest dose that is effective and safe. In this review, 400 µg of misoprostol were found to be safer than ≥ 600 µg and just as effective.