Olufemi T Oladapo1, Jennifer Blum2, Edgardo Abalos3, Babasola O Okusanya4. 1. UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), Department of Sexual and Reproductive Health and Research, World Health Organization, Geneva, Switzerland. 2. Gynuity Health Projects, New York, USA. 3. Centro Rosarino de Estudios Perinatales (CREP), Rosario, Argentina. 4. Experimental and Maternal Medicine Unit, Department of Obstetrics and Gynaecology, Faculty of Clinical Sciences, College of Medicine, University of Lagos, Idi-Araba, Lagos, Nigeria.
Abstract
BACKGROUND: Advance community distribution of misoprostol for preventing or treating postpartum haemorrhage (PPH) has become an attractive strategy to expand uterotonic coverage to places where conventional uterotonic use is not feasible. However, the value and safety of this strategy remain contentious. This is an update of a Cochrane Review first published in 2012. OBJECTIVES: To assess the effectiveness and safety of the strategy of advance misoprostol distribution to pregnant women for the prevention or treatment of PPH in non-facility births. SEARCH METHODS: For this update, we searched the Cochrane Pregnancy and Childbirth Trial Register, ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (19 December 2019), and reference lists of retrieved studies. SELECTION CRITERIA: We included randomised, cluster-randomised or quasi-randomised controlled trials of advance misoprostol distribution to pregnant women compared with usual (or standard) care for the prevention or treatment of PPH in non-facility births. We excluded studies without any form of random design and those that were available in abstract form only. DATA COLLECTION AND ANALYSIS: At least two review authors independently assessed trials for inclusion, extracted data and assessed the risk of bias in included studies. Two review authors independently assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: Two studies conducted in rural Uganda met the inclusion criteria for this review. One was a stepped-wedge cluster-randomised trial (involving 2466 women) which assessed the effectiveness and safety of misoprostol distribution to pregnant women compared with standard care for PPH prevention during non-facility births. The other study (involving 748 women) was a pilot individually randomised placebo-controlled trial which assessed the logistics and feasibility of community antenatal distribution of misoprostol, as well as the effectiveness and safety of self-administration of misoprostol for PPH prevention. Only 271 (11%) of women in the cluster-randomised trial and 299 (40%) of the women in the individually randomised trial had non-facility births. Data from the two studies could not be meta-analysed as the data available from the stepped-wedge trial were not adjusted for the study design. Therefore, the analysed effects of advance misoprostol distribution on PPH prevention largely reflect the findings of the placebo-controlled trial. Neither of the included studies addressed advance misoprostol distribution for the treatment of PPH. Primary outcomes Severe PPH was not reported in the studies. In both the intervention and standard care arms of the two studies, no cases of severe maternal morbidity or death were recorded among women who had a non-facility birth. Secondary outcomes Compared with standard care, it is uncertain whether advance misoprostol distribution has any effect on blood transfusion (no events, 1 study, 299 women), the number of women not using misoprostol (2% in the advance distribution group versus 4% in the usual care group; risk ratio (RR) 0.50, 95% confidence interval (CI) 0.13 to 1.95, 1 study, 299 women), the number of women not using misoprostol correctly (RR 4.86, 95% CI 0.24 to 100.46, 1 study, 290 women), inappropriate use of misoprostol (RR 4.97, 95% CI 0.24 to 102.59, 1 study, 299 women) or maternal transfer or referral to a health facility (RR 0.66, 95% CI 0.11 to 3.91, 1 study, 299 women). Compared with standard care, it is uncertain whether advance misoprostol provision increases the number of women experiencing minor adverse effects: shivering/chills (RR 1.84, CI 95% 1.35 to 2.50, 1 study, 299 women), fever (RR 1.87, 95% CI 1.16 to 3.00, 1 study, 299 women), or diarrhoea (RR 3.92, 95% CI 0.44 to 34.64, 1 study, 299 women); major adverse effects: placenta retention (RR 1.49, 95% CI 0.25 to 8.79, 1 study, 299 women) or hospital admission for longer than 24 hours (RR 0.99, 95% CI 0.66 to 15.73, 1 study, 299 women) after non-facility birth. For all the outcomes included in the 'Summary of findings' table, we assessed the certainty of the evidence as very low, according to GRADE criteria. AUTHORS' CONCLUSIONS: Whilst it might be considered reasonable and feasible to provide advance misoprostol to pregnant women where there are no suitable alternative options for the prevention or treatment of PPH, the evidence on the benefits and harms of this approach remains uncertain. Expansion of uterotonic coverage through this strategy should be cautiously implemented either in the context of rigorous research or with targeted monitoring and evaluation of its impact.
BACKGROUND: Advance community distribution of misoprostol for preventing or treating postpartum haemorrhage (PPH) has become an attractive strategy to expand uterotonic coverage to places where conventional uterotonic use is not feasible. However, the value and safety of this strategy remain contentious. This is an update of a Cochrane Review first published in 2012. OBJECTIVES: To assess the effectiveness and safety of the strategy of advance misoprostol distribution to pregnant women for the prevention or treatment of PPH in non-facility births. SEARCH METHODS: For this update, we searched the Cochrane Pregnancy and Childbirth Trial Register, ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (19 December 2019), and reference lists of retrieved studies. SELECTION CRITERIA: We included randomised, cluster-randomised or quasi-randomised controlled trials of advance misoprostol distribution to pregnant women compared with usual (or standard) care for the prevention or treatment of PPH in non-facility births. We excluded studies without any form of random design and those that were available in abstract form only. DATA COLLECTION AND ANALYSIS: At least two review authors independently assessed trials for inclusion, extracted data and assessed the risk of bias in included studies. Two review authors independently assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: Two studies conducted in rural Uganda met the inclusion criteria for this review. One was a stepped-wedge cluster-randomised trial (involving 2466 women) which assessed the effectiveness and safety of misoprostol distribution to pregnant women compared with standard care for PPH prevention during non-facility births. The other study (involving 748 women) was a pilot individually randomised placebo-controlled trial which assessed the logistics and feasibility of community antenatal distribution of misoprostol, as well as the effectiveness and safety of self-administration of misoprostol for PPH prevention. Only 271 (11%) of women in the cluster-randomised trial and 299 (40%) of the women in the individually randomised trial had non-facility births. Data from the two studies could not be meta-analysed as the data available from the stepped-wedge trial were not adjusted for the study design. Therefore, the analysed effects of advance misoprostol distribution on PPH prevention largely reflect the findings of the placebo-controlled trial. Neither of the included studies addressed advance misoprostol distribution for the treatment of PPH. Primary outcomes Severe PPH was not reported in the studies. In both the intervention and standard care arms of the two studies, no cases of severe maternal morbidity or death were recorded among women who had a non-facility birth. Secondary outcomes Compared with standard care, it is uncertain whether advance misoprostol distribution has any effect on blood transfusion (no events, 1 study, 299 women), the number of women not using misoprostol (2% in the advance distribution group versus 4% in the usual care group; risk ratio (RR) 0.50, 95% confidence interval (CI) 0.13 to 1.95, 1 study, 299 women), the number of women not using misoprostol correctly (RR 4.86, 95% CI 0.24 to 100.46, 1 study, 290 women), inappropriate use of misoprostol (RR 4.97, 95% CI 0.24 to 102.59, 1 study, 299 women) or maternal transfer or referral to a health facility (RR 0.66, 95% CI 0.11 to 3.91, 1 study, 299 women). Compared with standard care, it is uncertain whether advance misoprostol provision increases the number of women experiencing minor adverse effects: shivering/chills (RR 1.84, CI 95% 1.35 to 2.50, 1 study, 299 women), fever (RR 1.87, 95% CI 1.16 to 3.00, 1 study, 299 women), or diarrhoea (RR 3.92, 95% CI 0.44 to 34.64, 1 study, 299 women); major adverse effects: placenta retention (RR 1.49, 95% CI 0.25 to 8.79, 1 study, 299 women) or hospital admission for longer than 24 hours (RR 0.99, 95% CI 0.66 to 15.73, 1 study, 299 women) after non-facility birth. For all the outcomes included in the 'Summary of findings' table, we assessed the certainty of the evidence as very low, according to GRADE criteria. AUTHORS' CONCLUSIONS: Whilst it might be considered reasonable and feasible to provide advance misoprostol to pregnant women where there are no suitable alternative options for the prevention or treatment of PPH, the evidence on the benefits and harms of this approach remains uncertain. Expansion of uterotonic coverage through this strategy should be cautiously implemented either in the context of rigorous research or with targeted monitoring and evaluation of its impact.
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