Quality of oxytocin and misoprostol in health facilities of Rwanda.

Sustainable Development Goal 3.1 calls for a reduction of the maternal mortality ratio to less than 70 per 100,000 live births by 2030. The most important cause of maternal mortality is post-partum haemorrhage (PPH). Oxytocin injections and misoprostol tablets are medicines of first choice for the management of PPH in low- and middle-income countries (LMICs). Unfortunately, both substances are chemically unstable, and previous studies have revealed serious quality problems of these medicines in LMICs. The present study is the first report on their quality in Rwanda. From 40 randomly selected health facilities (hospitals, health centers, retail pharmacies and private clinics) in different parts of Rwanda, as well as from six wholesalers and government stores, oxytocin injections and misoprostol tablets were collected. Oxytocin storage temperatures in the health facilities were monitored for six months using temperature data loggers, and found to correctly follow the storage requirements stated by the manufacturers (2-8°C, or room temperature) with few minor deviations. Oxytocin injections (57 samples, representing seven batches of four brands) were tested for their oxytocin content and pH value according to the United States Pharmacopeia. Twenty-four samples from three European manufacturers passed all tests. However, all nine samples of one batch of a Chinese manufacturer showed an excessive content of oxytocin (range 117.2-121.5% of the declared amount). Another batch of the same manufacturer showed extreme variations of the concentration of the preservative benzyl alcohol. Misoprostol tablets (25 samples, representing ten batches of six brands) were tested for content and dissolution according to the International Pharmacopoeia. Fifteen samples passed, but all 10 samples of two brands from India failed with extreme deviations, containing only 42.5-48.7% of the stated amount of misoprostol. In conclusion, oxytocin quality in Rwanda was better than reported from other African countries. However, two extremely substandard brands of misoprostol tablets were found. The Rwandan authorities reacted quickly and efficiently, and recalled these substandard medicines from the market. For oxytocin and misoprostol, with their well-known problems of quality and stability, procurement should possibly be restricted to medicines which are WHO-prequalified or which have been manufactured in countries with stringent regulatory authorities.

Quality, availability and storage conditions of oxytocin and misoprostol in Malawi.

BACKGROUND: Postpartum haemorrhage (PPH) is the leading cause of maternal mortality in low- and middle-income countries (LMICs). Oxytocin and misoprostol are used for the prevention and treatment of PPH. However, both medicines are chemically unstable and sensitive to environmental conditions. Previous studies reported a high prevalence of substandard oxytocin and misoprostol preparations in LMICs. METHODS: In randomly selected health facilities of four districts of Malawi, the availability of oxytocin and misoprostol was determined, and the knowledge of health workers on storage requirements and use of oxytocics was assessed. Temperature loggers were used to record the storage temperature of oxytocics. Samples of oxytocin injections and misoprostol tablets were collected from the health facilities and from wholesalers. Oxytocin samples were analysed for identity, assay (= quantity of oxytocin) and for pH value according to United States Pharmacopeia 40. Misoprostol samples were analysed for identity, assay, dissolution and related substances according to the International Pharmacopeia 2017. RESULTS: All visited hospitals and health centers had oxytocin available. At non-refrigerated storage sites, the recorded mean kinetic temperature exceeded the oxytocic's storage temperature stated on the labels in 42% of the sites. At refrigerated storage sites, the required temperature of 2-8 °C was exceeded in 33% of the sites. Out of 65 oxytocin samples, 7 (11%) showed moderate deviations from specification, containing 82.2-86.8% of the declared amount of oxytocin. Out of 30 misoprostol samples, 5 (17%) showed extreme deviations, containing only 12.7-30.2% of the declared amount. The extremely substandard misoprostol was reported to the national authorities and to WHO, leading to an immediate recall of the respective brand in Malawi. The UK-based distributor of this brand closed its business shortly thereafter. CONCLUSION: Availability of oxytocin was excellent in Malawi, and its quality was better than reported in previous studies in other LMICs. However, storage conditions at the health facilities often did not meet the requirements. Extremely substandard misoprostol tablets were found, representing a serious risk to maternal health. This shows the need for continued efforts for quality assurance in medicine procurement and registration, as well as for post-marketing surveillance.

Challenges and Successes of Distributing Birth Kits with Misoprostol to Reduce Maternal Mortality in Rural Tanzania.

The Saving Mothers Project was conducted from September 2015 to March 2017 in Bunda and Tarime Districts, Mara Region, Tanzania. The purpose of this project was to train community health workers (CHWs) to use mobile phones applications to register and educate pregnant women about safe deliveries and encourage them to access skilled health care providers for antenatal care and delivery, and to provide nurses and CHWs with clean birth kits with misoprostol to distribute to women. The birth kits were for use in case women could not access the health facility, or if the health facility was lacking supplies at the time of delivery. The overall goal of the study was to reduce the maternal mortality rate by increasing women's access to health services where possible, and to clean supplies when a non-facility birth was unavoidable. This paper reports on a mixed methods evaluation of the project including a survey of over two thousand four hundred women, and focus groups with women, community health workers, and nurses participating in the project. The results of the survey and focus groups demonstrate a high degree of satisfaction with the birth kits and misoprostol and an increase in facility birth rates where the project was implemented. Differences between the two districts illustrate that policy maker support is key to successful implementation.

Effect of community-based distribution of misoprostol on facility delivery: a scoping review.

INTRODUCTION: Community distribution of misoprostol to pregnant women in advance of labor is one of the compelling strategies for preventing postpartum hemorrhage. Concerns have been reported that misoprostol distribution could reduce facility delivery or lead to misuse of the medication. This scoping review was conducted to synthesize the evidence on the effect of community-based misoprostol distribution on rates of facility delivery, and to assess the frequency of mothers taking distributed misoprostol before delivery, and any harmful outcomes of such misuse. METHODS: We included peer-reviewed articles on misoprostol implementation from PubMed, Cochrane Review Library, Popline, and Google Scholars. Narrative synthesis was used to analyze and interpret the findings, in which quantitative and qualitative syntheses are integrated. RESULTS: Three qualitative studies, seven observational studies, and four experimental or quasi-experimental studies were included in this study. All before-after household surveys reported increased delivery coverage after the intervention: ranging from 4 to 46 percentage points at the end of the intervention when compared to the baseline. The pooled analysis of experimental and quasi-experimental studies involving 7564 women from four studies revealed that there was no significant difference in rates of facility delivery among the misoprostol and control groups [OR 1.011; 95% CI: 0.906-1.129]. A qualitative study among health professionals also indicated that community distribution of misoprostol for the prevention of postpartum hemorrhage is acceptable to community members and stakeholders and it is a feasible interim solution until access to facility birth increases. In the community-based distribution of misoprostol programs, self-administration of misoprostol by pregnant women before delivery was reported in less than 2% of women, among seven studies involving 11,108 mothers. Evidence also shows that most women who used misoprostol pills, used them as instructed. No adverse outcomes from misuse in either of the studies reviewed. CONCLUSIONS: The claim that community-based distribution of misoprostol would divert women who would have otherwise had institutional deliveries to have home deliveries and promote misuse of the medication are not supported with evidence. Therefore, community-based distribution of misoprostol can be an appropriate strategy for reducing maternal deaths which occur due to postpartum hemorrhages, especially in resource-limited settings.

Modeling patient access to therapeutic oxytocin in Zanzibar, Tanzania.

BACKGROUND: Our objective is to estimate the effects of therapeutic oxytocin supply chain factors and social determinants of health on patient access to oxytocin in low-income settings using system dynamics modeling. Postpartum hemorrhage (PPH), a major cause of maternal mortality disproportionately affects women in low and middle income countries (LMICs). The World Health Organization recommends therapeutic oxytocin as the frontline uterotonic for PPH management and prevention. However, lack of access to quality therapeutic oxytocin in Tanzania, and throughout Sub-Saharan Africa, continues to result in a high number of preventable maternal deaths. METHODS: We used publicly available data from Zanzibar and Sub-Saharan Africa, literature review, oxytocin degradation kinetics and previously developed systems dynamics models to understand the barriers in patient access to quality therapeutic oxytocin. RESULTS: The model makes four basic predictions. First, there is a major gap between therapeutic oxytocin procurement and availability. Second, it predicts that at current population increase rates, oxytocin supply will have to be doubled in the next 30 years. Third, supply and storage temperature until 30 °C has minimal effect on oxytocin quality and finally distance of 5 km or less to birthing facility has a small effect on overall access to oxytocin. CONCLUSIONS: The model provides a systems level approach to therapeutic oxytocin access, incorporating supply and procurement, socio-economic factors, as well as storage conditions to understand how women's access to oxytocin over time can be sustained for better health outcomes.

Quality medicines in maternal health: results of oxytocin, misoprostol, magnesium sulfate and calcium gluconate quality audits.

BACKGROUND: The high level of maternal mortality and morbidity as a result of complications due to childbirth is unacceptable. The impact of quality medicines in the management of these complications cannot be overemphasized. Most of those medicines are sensitive to environmental conditions and must be handled properly. In this study, the quality of oxytocin injection, misoprostol tablets, magnesium sulfate, and calcium gluconate injections was assessed across the six geopolitical zones of Nigeria. METHOD: Simple, stratified random sampling of health facilities in each of the political zones of Nigeria. Analysis for identification and content of active pharmaceutical ingredient was performed using high-performance liquid chromatography procedures of 159 samples of oxytocin injection and 166 samples of misoprostol tablets. Titrimetric methods were used to analyze 164 samples of magnesium sulfate and 148 samples of calcium gluconate injection. Other tests included sterility, pH measurement, and fill volume. RESULTS: Samples of these commodities were procured mainly from wholesale and retail pharmacies, where these were readily available, while the federal medical centers reported low availability. Approximately, 74.2% of oxytocin injection samples failed the assay test, with the northeast and southeast zones registering the highest failure rates. Misoprostol tablets recorded a percentage failure of 33.7%. Magnesium sulfate and Calcium gluconate injection samples recorded a failure rate of 6.8% and 2.4%, respectively. CONCLUSION: The prevalence of particularly of oxytocin and misoprostol commodities was of substandard quality. Strengthening the supply chain of these important medicines is paramount to ensuring their effectiveness in reducing maternal deaths in Nigeria.

Postpartum hemorrhage prevention in Nepal: a program assessment.

BACKGROUND: In 2009, the Nepal Ministry of Health and Population launched a national program for prevention of postpartum hemorrhage (PPH) during home births that features advance distribution of misoprostol to pregnant women. In the years since, the government has scaled-up the program throughout much of the country. This paper presents findings from the first large-scale assessment of the effectiveness of the advance distribution program. METHODS: Data collection was carried out in nine districts and all three ecological zones. To assess knowledge, receipt and use of misoprostol, household interviews were conducted with 2070 women who had given birth within the past 12 months. To assess supply and provision of misoprostol, interviews were conducted with 270 Female Community Health Volunteers (FCHVs) and staff at 99 health facilities. RESULTS: Among recently delivered women, only 15% received information about misoprostol and 13% received misoprostol tablets in advance of delivery. Yet 87% who received advance misoprostol and delivered at home used it for PPH prevention. Among FCHVs, 96% were providing advance misoprostol for PPH prevention; however 81% had experienced at least one misoprostol stock out within the past year. About one-half of FCHVs were providing incomplete information about the use of misoprostol; in addition, many did not discuss side effects, how to recognize PPH or where to go if PPH occurs. Among health facilities, just one-half had sufficient misoprostol stock, while 95% had sufficient oxytocin stock, at the time of this assessment. CONCLUSIONS: In Nepal, women who receive advance misoprostol are both willing and able to use the medication for PPH prevention during home births. However the supply and personnel challenges identified raise questions about scalability and impact of the program over the long-term. Further assessment is needed.

Social networks and health policy: the case of misoprostol and the WHO model essential medicine list.

The WHO Essential Medicines List (EML) was established to help countries prioritise medicines according to their health care needs. Selection for the List is based on rigorous scrutiny of public health relevance, evidence on efficacy and safety, and comparative cost effectiveness. The WHO ideal is that a medicine and its efficacy are based on science, but in reality a medicine has a social life and the acceptance of a pharmaceutical intervention involves the interaction of a wide array of governmental and civil society organisations, and industry. Misoprostol is a medicine widely used for both abortion and prevention of postpartum haemorrhage in low income countries. Although the evidence for the latter is highly contested it was nevertheless added to the WHO EML in 2011. We use social network analysis to examine the social, political and economic field surrounding the WHO EML applications and health policy. We describe a chronology of the drug's use and of the applications to the WHO EML and carry out a social network analysis of the organisations and individuals involved in the applications, research and dissemination. The research identified a network of 238 organisations and individuals involved in the promotion of misoprostol for postpartum haemorrhage and present at the time of the WHO EML applications. There is a strong interdependency between the funding bodies, civil society organisations, researchers and clinician organisations. The research was part of an EU FP7 funded project on Accessing Medicines in Africa and South Asia (2010-2013).

Civil Society Organizations and medicines policy change: a case study of registration, procurement, distribution and use of misoprostol in Uganda.

Misoprostol use for postpartum haemorrhage (PPH) has been promoted by Civil Society Organizations (CSOs) since the early 2000s. Yet, CSOs' role in improving access to misoprostol and shaping health policy at global and national levels is not well understood. We document the introduction of misoprostol in Uganda in 2008 from its registration, addition to treatment guidelines and national Essential Medicines List (EML), to its distribution and use. We then analyse the contribution of CSOs to this health policy change and service provision. Policy documents, procurement data and 82 key informant interviews with government officials, healthcare providers, and CSOs in four Ugandan districts of Kampala, Mbarara, Apac, Bundibugyo were collected between 2010 and 2013. Five key CSOs promoted and accelerated the rollout of misoprostol in Uganda. They supported the registration of misoprostol with the National Drug Authority, the development of clinical guidelines, and the piloting and training of health care providers. CSOs and National Medical Stores were procuring and distributing misoprostol country-wide to health centres two years before it was added to the clinical guidelines and EML of Uganda and in the absence of good evidence. The evidence suggests an increasing trend of misoprostol procurement and availability over the medicine of choice, oxytocin. This shift in national priorities has serious ramifications for maternal health care that need urgent evaluation. The absence of clinical guidelines in health centres and the lack of training preclude rational use of misoprostol. CSOs shifted their focus from the public to the private sector, where some of them continue to promote its use for off-label indications including induction of labour and abortion. There is an urgent need to build capacity to improve the robustness of the national and local institutions in assessing the safety and effectiveness of all medicines and their indications in Uganda.

Accessibility and potency of uterotonic drugs purchased by simulated clients in four districts in India.

BACKGROUND: Surveillance of drug quality for antibiotics, antiretrovirals, antimalarials and vaccines is better established than surveillance for maternal health drugs in low-income countries, particularly uterotonic drugs for the prevention and treatment of postpartum hemorrhage. The objectives of this study are to: assess private sector accessibility of four drugs used for uterotonic purposes (oxytocin, methylergometrine, misoprostol, valethamate bromide); and to assess potency of oxytocin and methylergometrine ampoules purchased by simulated clients. METHODS: The study was conducted in Hassan and Bagalkot districts in Karnataka state and Agra and Gorakhpur districts in Uttar Pradesh state. A sample of 877 private pharmacies was selected (using a stratified, systematic sampling with random start), among which 847 were successfully visited. The target sample size for assessment of accessibility was 50 pharmacies per drug, per district. The target sample size for potency assessment was 100 purchases each of oxytocin and methylergometrine across all districts. Successful drug purchases varied by state. RESULTS: In Agra and Gorakhpur, 90%-100% of visits for each of the drugs resulted in a purchase. In Bagalkot and Hassan, only 29%-52% of visits for each drug resulted in a purchase. Regarding potency, the percent of active pharmaceutical ingredient was assessed using United States Pharmacopeia monograph #33 for both drugs; 193 and 188 ampoules of oxytocin and methylergometrine, respectively, were assessed. The percent of oxytocin ampoules outside manufacturer specification ranged from 33%-40% in Karnataka and from 22%-50% in Uttar Pradesh. In Bagalkot and Hassan, 96% and 100% of the methylergometrine ampoules were outside manufacturer specification, respectively. In Agra and Gorakhpur, 54% and 44% were outside manufacturer specification, respectively. CONCLUSION: Private sector accessibility of uterotonic drugs in study districts in Karnataka warrants attention. Most importantly, interventions to assure quality oxytocin and particularly methylergometrine are needed in study districts in both states.

Assessment of facility readiness and provider preparedness for dealing with postpartum haemorrhage and pre-eclampsia/eclampsia in public and private health facilities of northern Karnataka, India: a cross-sectional study.

BACKGROUND: The maternal mortality ratio in India has been declining over the past decade, but remains unacceptably high at 212 per 100,000 live births. Postpartum haemorrhage (PPH) and pre- eclampsia/eclampsia contribute to 40% of all maternal deaths. We assessed facility readiness and provider preparedness to deal with these two maternal complications in public and private health facilities of northern Karnataka state, south India. METHODS: We undertook a cross-sectional study of 131 primary health centres (PHCs) and 148 higher referral facilities (74 public and 74 private) in eight districts of the region. Facility infrastructure and providers' knowledge related to screening and management of complications were assessed using facility checklists and test cases, respectively. We also attempted an audit of case sheets to assess provider practice in the management of complications. Chi square tests were used for comparing proportions. RESULTS: 84.5% and 62.9% of all facilities had atleast one doctor and three nurses, respectively; only 13% of higher facilities had specialists. Magnesium sulphate, the drug of choice to control convulsions in eclampsia was available in 18% of PHCs, 48% of higher public facilities and 70% of private facilities. In response to the test case on eclampsia, 54.1% and 65.1% of providers would administer anti-hypertensives and magnesium sulphate, respectively; 24% would administer oxygen and only 18% would monitor for magnesium sulphate toxicity. For the test case on PPH, only 37.7% of the providers would assess for uterine tone, and 40% correctly defined early PPH. Specialists were better informed than the other cadres, and the differences were statistically significant. We experienced generally poor response rates for audits due to non-availability and non-maintenance of case sheets. CONCLUSIONS: Addressing gaps in facility readiness and provider competencies for emergency obstetric care, alongside improving coverage of institutional deliveries, is critical to improve maternal outcomes. It is necessary to strengthen providers' clinical and problem solving skills through capacity building initiatives beyond pre-service training, such as through onsite mentoring and supportive supervision programs. This should be backed by a health systems response to streamline staffing and supply chains in order to improve the quality of emergency obstetric care.

Advance distribution of misoprostol for prevention of postpartum hemorrhage (PPH) at home births in two districts of Liberia.

BACKGROUND: A postpartum hemorrhage prevention program to increase uterotonic coverage for home and facility births was introduced in two districts of Liberia. Advance distribution of misoprostol was offered during antenatal care (ANC) and home visits. Feasibility, acceptability, effectiveness of distribution mechanisms and uterotonic coverage were evaluated. METHODS: Eight facilities were strengthened to provide PPH prevention with oxytocin, PPH management and advance distribution of misoprostol during ANC. Trained traditional midwives (TTMs) as volunteer community health workers (CHWs) provided education to pregnant women, and district reproductive health supervisors (DRHSs) distributed misoprostol during home visits. Data were collected through facility and DRHS registers. Postpartum interviews were conducted with a sample of 550 women who received advance distribution of misoprostol on place of delivery, knowledge, misoprostol use, and satisfaction. RESULTS: There were 1826 estimated deliveries during the seven-month implementation period. A total of 980 women (53.7%) were enrolled and provided misoprostol, primarily through ANC (78.2%). Uterotonic coverage rate of all deliveries was 53.5%, based on 97.7% oxytocin use at recorded facility vaginal births and 24.9% misoprostol use at home births. Among 550 women interviewed postpartum, 87.7% of those who received misoprostol and had a home birth took the drug. Sixty-three percent (63.0%) took it at the correct time, and 54.0% experienced at least one minor side effect. No serious adverse events reported among enrolled women. Facility-based deliveries appeared to increase during the program. CONCLUSIONS: The program was moderately effective at achieving high uterotonic coverage of all births. Coverage of home births was low despite the use of two channels of advance distribution of misoprostol. Although ANC reached a greater proportion of women in late pregnancy than home visits, 46.3% of expected deliveries did not receive education or advance distribution of misoprostol. A revised community-based strategy is needed to increase advance distribution rates and misoprostol coverage rates for home births. Misoprostol for PPH prevention appears acceptable to women in Liberia. Correct timing of misoprostol self-administration needs improved emphasis during counseling and education.

Recommendations for scale-up of community-based misoprostol distribution programs.

Community-based distribution of misoprostol for prevention of postpartum hemorrhage (PPH) in resource-poor settings has been shown to be safe and effective. However, global recommendations for prenatal distribution and monitoring within a community setting are not yet available. In order to successfully translate misoprostol and PPH research into policy and practice, several critical points must be considered. A focus on engaging the community, emphasizing the safe nature of community-based misoprostol distribution, supply chain management, effective distribution, coverage, and monitoring plans are essential elements to community-based misoprostol program introduction, expansion, or scale-up.

WHO recommendations for misoprostol use for obstetric and gynecologic indications.

BACKGROUND: Misoprostol, a prostaglandin E1 analog, stimulates uterine contractility and cervical ripening. A number of randomized trials and systematic reviews have evaluated its use in obstetric and gynecologic conditions. Misoprostol is inexpensive, stable at room temperature, and available in more than 80 countries, making it particularly useful in resource-poor settings. WHO recognizes the crucial role of misoprostol in reproductive health and has incorporated recommendations for its use into 4 reproductive health guidelines focused on induction of labor, prevention and treatment of postpartum hemorrhage, and management of spontaneous and induced abortion. METHODS AND RESULTS: All guidelines were prepared in accordance with the WHO Handbook for Guideline Development. The process included: identification of priority questions and critical outcomes; retrieval of evidence; assessment and synthesis of evidence; formulation of recommendations; and planning for dissemination, implementation, impact evaluation, and updating. The present report summarizes recommendations for misoprostol use in line with each guideline. CONCLUSION: The present comprehensive reference document was designed to enable clinicians and policy makers to quickly access and compare recommendations for the use of misoprostol in various reproductive health settings.

Misoprostol for postpartum hemorrhage prevention at home birth: an integrative review of global implementation experience to date.

BACKGROUND: Hemorrhage continues to be a leading cause of maternal death in developing countries. The 2012 World Health Organization guidelines for the prevention and management of postpartum hemorrhage (PPH) recommend oral administration of misoprostol by community health workers (CHWs). However, there are several outstanding questions about distribution of misoprostol for PPH prevention at home births. METHODS: We conducted an integrative review of published research studies and evaluation reports from programs that distributed misoprostol at the community level for prevention of PPH at home births. We reviewed methods and cadres involved in education of end-users, drug administration, distribution, and coverage, correct and incorrect usage, and serious adverse events. RESULTS: Eighteen programs were identified; only seven reported all data of interest. Programs utilized a range of strategies and timings for distributing misoprostol. Distribution rates were higher when misoprostol was distributed at a home visit during late pregnancy (54.5-96.9%) or at birth (22.5-83.6%), compared to antenatal care (ANC) distribution at any ANC visit (22.5-49.1%) or late ANC visit (21.0-26.7%). Coverage rates were highest when CHWs and traditional birth attendants distributed misoprostol and lower when health workers/ANC providers distributed the medication. The highest distribution and coverage rates were achieved by programs that allowed self-administration. Seven women took misoprostol prior to delivery out of more than 12,000 women who were followed-up. Facility birth rates increased in the three programs for which this information was available. Fifty-one (51) maternal deaths were reported among 86,732 women taking misoprostol: 24 were attributed to perceived PPH; none were directly attributed to use of misoprostol. Even if all deaths were attributable to PPH, the equivalent ratio (59 maternal deaths/100,000 live births) is substantially lower than the reported maternal mortality ratio in any of these countries. CONCLUSIONS: Community-based programs for prevention of PPH at home birth using misoprostol can achieve high distribution and use of the medication, using diverse program strategies. Coverage was greatest when misoprostol was distributed by community health agents at home visits. Programs appear to be safe, with an extremely low rate of ante- or intrapartum administration of the medication.

Misoprostol for preventing and treating postpartum hemorrhage in the community: a closer look at the evidence.

The lack of clear interpretation of clinical and operational evidence on misoprostol use for postpartum hemorrhage (PPH) in the community may jeopardize the realization of its full potential for improving women's survival. This paper highlights the usefulness of misoprostol in addressing PPH in the community within the limits of available research evidence. There is now substantial evidence to support the beneficial effects of 600 µg of oral misoprostol for PPH prevention in the community, with a trend toward better protection against severe PPH morbidity, and particularly when administered by less skilled or lay caregivers. Although there is tangible evidence to show that 800 µg of sublingual misoprostol has important benefits for PPH treatment where there is no access to oxytocin, there is presently no direct evidence to indicate that less skilled or lay caregivers can safely use it to treat PPH in the community. Operational research evidence indicates that advance community distribution of misoprostol to pregnant women for postpartum self-use is a feasible strategy to ensure availability of the drug at the time of birth. The evidence is, however, limited by its quality to establish whether the benefits of such a strategy truly outweigh the potential harms. It is time for the international community to focus on improving PPH-related outcomes by scaling up what is currently guided by hard evidence and join forces to address unanswered questions through high-quality research.

Advance misoprostol distribution for preventing and treating postpartum haemorrhage.

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. OBJECTIVES: To assess the effectiveness and safety of a strategy of advance misoprostol distribution for PPH prevention and treatment in non-facility births. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (5 October 2011). We did not apply any language restrictions. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials of advance misoprostol distribution to lay health workers or pregnant women compared with usual care for PPH prevention or treatment in non-facility births. We excluded studies without any form of random design. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial eligibility for inclusion. MAIN RESULTS: The search strategies identified three studies. None of the studies met the inclusion criteria. AUTHORS' CONCLUSIONS: There is no evidence from randomised or quasi-randomised trials on the benefits or risks of a strategy of advance misoprostol distribution for PPH prevention or treatment in non-facility births. In view of the increasing interest to scale up this strategy, there is an urgent need for large and well-designed randomised trials to evaluate its comparative benefits and risks.

Community-based availability of misoprostol: is it safe?

This paper evaluates the safety and acceptability of long-term community-based use of misoprostol for management of postpartum hemorrhage (PPH) in home-births, by comparing deliveries with and without misoprostol use in communities of Kigoma, Tanzania. We administered a standardized survey instrument to women who delivered between August 2004 and May 2007. 940 women completed questionnaires, corresponding to 950 deliveries. Findings showed that the majority of TBAs administered misoprostol at the correct time (76%). Receipt of three or five tablets was most commonly reported (47% and 43% respectively). Misoprostol users were significantly more likely to experience shivering, high temperature, nausea, and vomiting after delivery; adjustment for gynecological history and delivery characteristics revealed no significant differences in experience of symptoms. Misoprostol was highly acceptable to all women surveyed. Misoprostol at the community level is a safe intervention.