We set out to determine the safety and effectiveness of giving pregnant women a medication called misoprostol to keep, so they have it ready to prevent or treat excessive bleeding immediately after birth.
What is the issue?
The medications oxytocin and ergometrine are commonly used to help reduce blood loss in the first 24 hours after giving birth. These require a trained health professional to be present as they are given by injection immediately after the birth. They also need to be kept in the refrigerator to remain effective.
Misoprostol is another medication that helps the womb to contract strongly after birth and reduce excess bleeding. It can be given by mouth and does not need refrigeration. This makes it easier to use than oxytocin and ergometrine, in parts of the world where refrigeration and trained health professionals are not readily available. The main side effects of misoprostol are generally self-limiting and do not require treatment with further medication.
Why is this important?
Excessive blood loss, or postpartum haemorrhage, remains the leading cause of maternal death worldwide. Most of these deaths occur in remote settings in Africa and Asia, where resources are poor and home births without a skilled birth attendant are common.
Having misoprostol available for use by pregnant women and community and lay health workers could be a way of avoiding excessive blood loss and death after giving birth. Misoprostol may, however, cause harm to women and their babies if used for other purposes such as to start labour before its natural onset.
What evidence did we find?
We searched for evidence on 19 December 2019. We identified two studies from rural Uganda involving 3214 women who were randomised (assigned by chance) to receive and keep misoprostol tablets or receive standard care for preventing excessive bleeding after birth. However, only 570 of the women enrolled in these studies gave birth outside of a health facility, which is what we were investigating.
We were unable to analyse most of the information from one study as it was not separated out by birth setting (health facility versus non-facility) and not well adjusted for the type of study design. Therefore, the analysed information in our review largely reflects the findings of one study.
No serious maternal ill health or deaths were reported in the two studies. One of the main outcomes of the review, blood loss of at least 1000 mL, was not reported. Other results were from one of the studies (299 women) that used a placebo (dummy pill) in the group who did not receive misoprostol. The certainty of the evidence was very low and the findings were variable. It is unclear whether giving women misoprostol in advance affected the number of women who used misoprostol, used it correctly and appropriately, or were referred to a health facility. The number of women who experienced side effects, and newborns with poor outcomes, was not clearly different between those who received misoprostol in advance and those who received standard care.
What does this mean?
Although this update supports the feasibility of a strategy of giving women misoprostol tablets to use after birth outside of a health facility, the evidence on the benefits of this approach remains uncertain. Efforts to scale up this strategy as part of reducing maternal deaths in remote regions should be done cautiously through targeted monitoring and evaluation, or with large-scale research to resolve the uncertainties.
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.
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.
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.
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.
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.
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.
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.
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.
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.