BackgroundMeta-analyses of postpartum blood loss and the effect of uterotonics are biased by visually estimated blood loss.ObjectivesTo conduct a systematic review of measured postpartum blood loss with and without prophylactic uterotonics for prevention of postpartum haemorrhage (PPH).Search strategyWe searched Medline and PubMed terms (labour stage, third) AND (ergonovine, ergonovine tartrate, methylergonovine, oxytocin, oxytocics or misoprostol) AND (postpartum haemorrhage or haemorrhage) and Cochrane reviews without any language restriction.Selection criteriaRefereed publications in the period 1988–2007 reporting mean postpartum blood loss, PPH (≥500 ml) or severe PPH (≥1000 ml) following vaginal births.Data collection and analysisRaw data were abstracted into Excel by one author and then reviewed by a co-author. Data were transferred to SPSS 17.0, and copied into RevMan 5.0 to perform random effects meta-analysis.Main resultsThe distribution of average blood loss (29 studies) is similar with any prophylactic uterotonic, and is lower than without prophylaxis. Compared with no uterotonic, oxytocin and misoprostol have lower PPH (OR 0.43, 95% CI 0.23–0.81; OR 0.73, 95% CI 0.50–1.08, respectively) and severe PPH rates (OR 0.61, 95% CI 0.29–1.29; OR 0.74, 95% CI 0.52–1.04, respectively). Oxytocin has lower PPH (OR 0.65, 95% CI 0.60–0.70) and severe PPH (OR 0.71, 95% CI 0.56–0.91) rates than misoprostol, but not in developing countries.ConclusionOxytocin is superior to misoprostol in hospitals. Misoprostol substantially lowers PPH and severe PPH. A sound assessment of the relative merits of the two drugs is needed in rural areas of developing countries, where most PPH deaths occur.

Please cite this paper as: Bellad M, Tara D, Ganachari M, Mallapur M, Goudar S, Kodkany B, Sloan N, Derman R. Prevention of postpartum haemorrhage with sublingual misoprostol or oxytocin: a double‐blind randomised controlled trial. BJOG 2012;119:975–986. Objective  Sublingual misoprostol produces a rapid peak concentration, and is more effective than oral administration. We compared the postpartum measured blood loss with 400 μg powdered sublingual misoprostol and after standard care using 10 iu intramuscular (IM) oxytocin. Design  Double‐blind randomised controlled trial. Setting  A teaching hospital: J N Medical College, Belgaum, India. Sample  A cohort of 652 consenting eligible pregnant women admitted to the labour room. Methods  Subjects were assigned to receive the study medications and placebos within 1 minute of clamping and cutting the cord by computer‐generated randomisation. Chi‐square and bootstrapped Student’s t‐tests were used to test categorical and continuous outcomes, respectively. Main outcome measures  Measured mean postpartum blood loss and haemorrhage (PPH, loss ≥500 ml), >10% pre‐ to post‐partum decline in haemoglobin, and reported side effects. Results  The mean blood loss with sublingual misoprostol was 192 ± 124 ml (n = 321) and 366 ± 136 ml with oxytocin IM (n = 331, P ≤ 0.001). The incidence of PPH was 3.1% with misoprostol and 9.1% with oxytocin (P = 0.002). No woman lost ≥1000 ml of blood. We observed that 9.7% and 45.6% of women experienced a haemoglobin decline of >10% after receiving misoprostol and oxytocin, respectively (P ≤ 0.001). Side effects were significantly greater in the misoprostol group than in the oxytocin group. Conclusion  Unlike other studies, this trial found sublingual misoprostol more effective than intramuscular oxytocin in reducing PPH, with only transient side effects being greater in the misoprostol group. The sublingual mode and/or powdered formulation may increase the effectiveness of misoprostol, and render it superior to injectable oxytocin for the prevention of PPH. Further research is needed to confirm these results.

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