Community-based distribution of misoprostol for the prevention of postpartum hemorrhage: misconceptions related to misuse and diversion of facility birth

Introduction : In low-resource settings, most maternal deaths caused by hemorrhage, occur in poorly resourced facilities or outside of health facilities where there is no access to skilled obstetric care. Community distribution of misoprostol is one of the compelling strategies for preventing or treating postpartum hemorrhage to avert maternal deaths. This scoping review was conducted to synthesize existing evidence that shows the negative impact of community distribution of misoprostol on facility delivery and misuse for labor induction or pregnancy termination. Methods: We identied and included all peer-reviewed articles on misoprostol implementation from PubMed, Cochrane Review Library, Popline, and Google Scholars. Narrative synthesis was used to analyze and interpret the ndings in which quantitative and qualitative syntheses are integrated. Results: Three qualitative studies, six observational studies, and four experimental or quasi-experimental studies from Africa and Asia are 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 (5 studies). The pooled analysis of experimental and quasi-experimental involving 7,564 women from four of the studies revealed that there is no signicant difference in facility delivery among the misoprostol and control groups [OR 1.011; 95% CI: 0.906-1.129]. A qualitative study among 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 is improved. In the community-based distribution of misoprostol programs, administration of misoprostol before delivery was reported in less than 2% among seven studies involving 11,108 mothers. Evidence also shows that most women used misoprostol pills as instructed. No adverse outcomes from misuse in either of the studies reviewed. Conclusions: The claim that community-based distribution of misoprostol would divert institutional delivery strategies to home deliveries and promote misuse 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 where many deliveries take place outside of health facilities.


Introduction
Maternal mortality ratio (MMR) remains high in low-and-middle-income countries (LMICs) and continues to be a priority challenge in the Sustainable Development Goals (SDG) era [1]. Accordingly, to achieve the SDG of reducing the global MMR to 70 per 100,000 live births by 2030, LMICs needs to implement innovative and high impact interventions that aim at preventing and managing the main causes of maternal deaths and providing high-quality services in the continuum of maternity care [2,3]. Page 3/24 A wealth of evidence shows that hemorrhage is one of the major causes of maternal mortality [4][5][6][7]. More than two-thirds of maternal deaths due to hemorrhage occur during the postpartum period that accounts for a quarter of all maternal deaths [8,9,6]. Reports also show that postpartum hemorrhage (PPH) accounts for 15 % of maternal deaths in sub-Saharan African [6]. In Ethiopia, a systematic review of national evidence shows that PPH accounts for 30% of maternal deaths [10,11].
Most maternal deaths occurring due to PPH are in poorly resourced facilities or outside of a health facility where there is no access to skilled obstetric care [8,12,13]. Women who deliver at home face the highest risk of PPH as they do not benefit from the support of skilled birth attendants and are less likely to receive timely care and medications that prevent PPH [13]. Evidence shows that most PPH-associated deaths could be avoided if active management of third stage of labor (AMTSL) is implemented [14], adverse outcomes and complications are prevented or managed using safe drugs at community and facilities, and effective referral mechanism institutionalized during delivery and postpartum period [9].
Misoprostol distribution at community level is one of the effective interventions for preventing or treating PPH. Misoprostol has been studied in different setups and is endorsed by the World Health Organization (WHO) as a solution for women who give birth in facilities without oxytocin or where there is low coverage of skilled attendance [15].
Clinical trials reveal the effectiveness and safety of community distribution of misoprostol [9,[16][17][18] where access to skilled birth attendance and oxytocin is limited.
However, community-based distribution of misoprostol is still the least prioritized intervention in the maternal survival strategies [19][20][21][22][23] due to concerns of policymakers' and practitioners' [18,17,23,13] that misoprostol distribution at community level might decrease facility deliveries, possiblity of misuse of misoprostol (taking the drug before delivery and using the drug for the purpose of inducing abortion), and lack of technologies and expertise to diagnose multiple pregnancies before using it at community levels in resource-limited settings [16,24]. Thus, a range of barriers are engrained in the health system and community and policy level impede access to misoprostol for prevention and/or Page 4/24 treatment of PPH due to: 1) absence of registration of misoprostol for the management of PPH [25,23], 2) fear and apprehensions of providers and policymakers regarding its use [25,23], 3) lack of evidence-based guidelines and provider training [23], and 4) inadequate staffing and lack of knowledge and skill of providers regarding causes of PPH and limited knowledge of the community regarding the dosage and timing of administration [25,16].
This scoping review was, therefore, conducted to synthesize existing evidence of whether community distribution of misoprostol negatively impacts utilization of facility delivery and results in misuse and increases risk of adverse pregnancy outcomes.

Criteria for inclusion
In this study, researchers used a scoping review methodology to get a wide range of information from both qualitative and quantitative studies. All types of literature on community-distribution of misoprostol for the prevention and/or treatment of PPH reported in English language with no specification on duration of publication were consulted.

Search strategy
We identified peer-reviewed articles on misoprostol implementation from PubMed, Cochrane Review Library, Popline, and Google Scholars which were made available until February 15, 2019. We also applied a snowball approach of searching from the references of papers of the initial search. America OR Middle East))) OR ((developing countr* OR less developed country * OR under developed country * OR underdeveloped country * OR middle income country * OR low income countr*)))))) AND First, any research output with the above-mentioned terms in either the title or abstract of the article is downloaded, and then a combination of these terms was also used to download more resources.

Data extraction and analysis
The form for abstracting data from reviewed literature was designed and review team members agreed on the contents of the form. Two reviewers (GT and YT) read each identified literature and populated the sheet designed for the purpose. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) diagram ( Figure 1) was used for the selection of articles to be used in this scoping review. In this study, a narrative synthesis was used to analyze and interpret the findings in which quantitative and qualitative syntheses are integrated. Descriptive information about the eligible studies was summarized using text and tables. Findings from the quantitative resources were narrated thematically followed by findings of qualitative resources. For intervention studies, a random-effects meta-analysis model [26,27] was used to pool the estimates of the facility birth outcome, accounting for the variability among studies using Stata v15 [28]. The results were presented as average treatment effects (odds ratio) with 95% confidence intervals.

Results
Description of studies Table 1 presents the characteristics of the studies included in this review. Seven of the studies were from Africa and the remaining seven were from Asia. Three qualitative studies [29,24,13], six observational studies [30][31][32][33][34][35], and four experimental or quasiexperimental studies [36][37][38][39] were included in this study. The results of our review are presented under three sections: 1) diversion of facility birth, 2) misuse, for purposes of either abortion or labor induction/augmentation, and 3) adverse events from misuse.

Diversion of facility birth
Ten studies (five observational before-after studies, four experimental or quasiexperimental trials, and one qualitative study) reported on the facility birth outcome [32,33,36,31,37,30,35,29,38,39]. All five before-after household surveys reported increased delivery coverage after the intervention: four percentage points increase in Nepal [33] and Liberia [32], 11% points in Afghanistan [31], 39% points in Ghana [30], and 46% points in India [35] at the end of the intervention when compared to the baseline ( Figure 2).  Table 2). A qualitative study among professionals also indicated that community distribution of misoprostol, for the prevention of PPH, is acceptable to community members and stakeholders and it is a feasible interim solution until access to facility birth is improved.
The study recognized misconceptions as barriers that might hinder community-based distribution of misoprostol [29]. Another study in Ethiopia reported regional differences in understanding the implementation strategy of misoprostol and a different concern among policymakers -that is fear of encouraging home birth [24].

Misuse
A program evaluation report in Nepal showed that there was no evidence to suggest that misoprostol distributed for the purpose of the prevention of PPH is being diverted for labor induction or pregnancy termination [40]. Moreover, as presented in Table 3, in the community-based distribution of misoprostol programs, administration of misoprostol before delivery was reported in less than 2% (n=17) among seven studies involving 11,108 mothers [30,31,34,32,38].
A cluster randomized controlled trial in Uganda [38] and an operations research in Ghana [30] reported that no woman took misoprostol before their babies' birth. Another before-after study in Afghanistan reported that only one out of 7,399 women in the study take misoprostol before the birth of her newborn [31]. Similarly, according to a trial in Uganda, only two out of 700 women took tablets before delivery [36]. In Liberia, only three of 265 women took misoprostol prior to giving birth [32]; while in Ethiopia, less than 2% of women took the tablets before birth [34] (Table 3). Evidence also shows that most women used the misoprostol pills as instructed [33,30,39]; unused doses were returned after birth to the point of distribution; and most others either threw it away or kept it [30,40]. However, qualitative studies in Ethiopia identified, lack of trust in women's capabilities to use misoprostol correctly [13] and fear of misuse [13,24], as a problem.

Adverse effects of misuse
No adverse outcomes of misuse were reported in either of the studies reviewed.

Discussion
This review shows that misoprostol community-based distribution programs demonstrated increments in coverage of facility-based births. The studies reviewed also find very few rates of administration of misoprostol before delivery and no adverse outcomes because of misuse. Despite the apparent prevailing fear of misoprostol misuse, diversion of facility birth, and adverse effects of its misuse [13,24,19]; this scoping review showed that, so far, community-based distribution of misoprostol did not negatively impact facility birth and did not promote misuse. Accordingly, the apparent prevailing fear of misoprostol misuse, diversion of facility birth, and adverse effects of its misuse are simply misconceptions and there is no evidence that supports the claim. As it is evident from a qualitative study in Ethiopia [24], these misconceptions arise from the health providers' perception but not from the women using misoprostol.
In addition, evidence shows that misoprostol is safe and effective for preventing and treating PPH in remote settings where both oxytocin and timely transfer to higher-level care are not available [41,18,23]. Previous studies also report that community health workers or other lower-level workers could safely administer misoprostol [15,29]. Women were found to have no major problem of misusing the drug and it was found to be acceptable by them [15]. Another rapid review of the literature showed that distribution of misoprostol in advance by lay health workers or self-administration were feasible and acceptable at all levels-end-user, health system, community, and policy [16,23].
However, there are concerns by policymakers, often unsupported by available evidence [23], about misoprostol distribution at community level that impede the strategy to be translated into effective policies, programs, and practice. The concerns are, fear of women using misoprostol for inducing abortion or labor and diversion of facility-based birth strategies to home deliveries [36,42,23]. A range of barriers including service delivery challenges, supply and procurement, financial, national and global policy environments, and those factors more closely connected to the end-user that impede access to a uterotonic for prevention and/or treatment of PPH for every woman [43]. These implementation barriers represent important threats to any community-based program and most of these barriers reflect existing health system weaknesses in many countries [16].
Community-based distribution of misoprostol is a compelling strategy parallel to strengthening healthcare facilities to increase institutional deliveries [19,23] to ensure universal access to uterotonics for every woman. A review by Hobday et al. recommends to simultaneously promote facility delivery and strengthen health systems to avail misoprostol at the community level [15]. It means, it is a complementary strategy for simultaneously increasing the availability of misoprostol and actively promoting facility births through increasing contact with pregnant women. And, their interaction offers the opportunity to promote early care-seeking and referral during pregnancy [16]. As such, the communitybased distribution of misoprostol, then, should include the promotion of facility-based birth [5,30,29] as a critical intervention. Successful implementation of the misoprostol distribution can be ensured by providing enabling environment through supportive policies, designing a formal plan for supplies, task shifting strategies and appropriate use of guidelines and protocols [25]. Moreover, strong leadership and political commitment, training, and community mobilization were identified as critical success factors [16].
This study provides critical information gaps to help policymakers and program managers to develop national policies and to strategize the implementation of community-based distribution of misoprostol to prevent PPH and reduce maternal mortality. It also suggests that the rates of administration of misoprostol before delivery and adverse outcomes of misuse of community-based distribution of misoprostol for home births are very low, especially when compared to the risks women encountered without access to uterotonics.
As such, community-based distribution of misoprostol is an appropriate strategy till facility delivery becomes a norm.
However, decision-makers are still reluctant and have encountered dilemmas of ethical decision to implement this strategy. National guidance and policies from higher level of the health system as well as creating opportunities for reflective discussions or policy dialogue, is thus important for virtuous public health practice.
Implementation research is needed to examine implementation challenges as well as to continually demystify the concerns regarding misuse of the drug. Close monitoring is also critical as part of the implementation of the strategy. Further research is needed on how community-based distribution of misoprostol would be effective in hard-to-reach areas where most women give birth at home and are areas characterized by weak health system, poor community health workers' performance, mobile lifestyle, and poor infrastructure.

Conclusions
Community-based distribution of misoprostol programs demonstrated an increase in coverage of facility-based births. This review also finds very few rates of administration of misoprostol before delivery and no adverse outcomes of misuse in either of the studies reviewed.
Fears of misuse of misoprostol and increased adverse pregnancy outcomes if distributed at community, are not supported by evidence. Therefore, community-based distribution of misoprostol can be an appropriate strategy for reducing maternal deaths caused by postpartum hemorrhages, especially in resource-limited settings where many deliveries take place outside of health facilities.

Abbreviations
Abbreviations AMTSL The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Competing Interests
The authors declare that they have no competing interests.

Funding
The authors declare that they did not receive funding for this research from any source.  Study ow diagram