• Hatem A Mousa, Jennifer Blum, Ghada Abou El Senoun, Haleema Shakur, and Zarko Alfirevic.
• University Department of Obstetrics and Gynaecology, Fetal and Maternal Medicine Unit, Leicester Royal Infirmary, Infirmary Square, Leicester, UK, LE1 5WW.
• Cochrane Db Syst Rev. 2014 Feb 13; 2014 (2): CD003249CD003249.

BackgroundPrimary postpartum haemorrhage (PPH) is one of the top five causes of maternal mortality in both developed and developing countries.ObjectivesTo assess the effectiveness and safety of any intervention used for the treatment of primary PPH.Search MethodsWe searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 August 2013).Selection CriteriaRandomised controlled trials comparing any interventions for the treatment of primary PPH.Data Collection And AnalysisWe assessed studies for eligibility and quality and extracted data independently. We contacted authors of the included studies to request more information.Main ResultsTen randomised clinical trials (RCTs) with a total of 4052 participants fulfilled our inclusion criteria and were included in this review.Four RCTs (1881 participants) compared misoprostol with placebo given in addition to conventional uterotonics. Adjunctive use of misoprostol (in the dose of 600 to 1000 mcg) with simultaneous administration of additional uterotonics did not provide additional benefit for our primary outcomes including maternal mortality (risk ratio (RR) 6.16, 95% confidence interval (CI) 0.75 to 50.85), serious maternal morbidity (RR 0.34, 95% CI 0.01 to 8.31), admission to intensive care (RR 0.79, 95% CI 0.30 to 2.11) or hysterectomy (RR 0.93, 95% CI 0.16 to 5.41).  Two RCTs (1787 participants) compared 800 mcg sublingual misoprostol versus oxytocin infusion as primary PPH treatment; one trial included women who had received prophylactic uterotonics, and the other did not. Primary outcomes did not differ between the two groups, although women given sublingual misoprostol were more likely to have additional blood loss of at least 1000 mL (RR 2.65, 95% CI 1.04 to 6.75). Misoprostol was associated with a significant increase in vomiting and shivering.Two trials attempted to test the effectiveness of estrogen and tranexamic acid, respectively, but were too small for any meaningful comparisons of pre-specified outcomes.One study compared lower segment compression but was too small to assess impact on primary outcomes.We did not identify any trials evaluating surgical techniques or radiological interventions for women with primary PPH unresponsive to uterotonics and/or haemostatics.Authors' ConclusionsClinical trials included in the current review were not adequately powered to assess impact on the primary outcome measures. Compared with misoprostol, oxytocin infusion is more effective and causes fewer side effects when used as first-line therapy for the treatment of primary PPH. When used after prophylactic uterotonics, misoprostol and oxytocin infusion worked similarly. The review suggests that among women who received oxytocin for the treatment of primary PPH, adjunctive use of misoprostol confers no added benefit.The role of tranexamic acid and compression methods requires further evaluation. Furthermore, future studies should focus on the best way to treat women who fail to respond to uterotonic therapy.

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