Description of studies
Table 1 presents the characteristics of the studies included in this review. Fourteen studies were included in the review. Seven of the studies were from Africa and the remaining seven were from Asia. Three qualitative studies [35, 26, 12], seven observational studies [36-42], and four experimental or quasi-experimental studies [43-46] were included in this review. All studies were published from 2006 to 2018.
Interventional activities in observational and experimental studies included training to health workers, antepartum and/or postpartum home visits, identification of pregnant women, provision of prenatal education, community sensitization, and distribution of 600μg misoprostol to women.
Methodological quality of included studies
According to the JBI quality appraisal tool, two of the RCTs scored high quality (88%) and a quasi-experimental study scored medium (61%). On the other hand, the cluster RCT study included scored low (46%) where it had baseline imbalances as well as lacked masking of study of participants, personnel, and assessors [43]. All experimental and quasi-experimental studies provided adequate information about random sequence generation as well as thorough description of the interventions.
Overall, the seven cross-sectional studies scored medium quality (70%) in which most lacked strategies to deal with confounding as well as some lacked appropriate use of statistical methods of analysis. Likewise, all qualitative studies scored medium (65%) in which they are subjected to reporting bias in which philosophical perspectives as well as researchers’ experiences, beliefs, wishes, attitudes, culture, views, and personality not stated which might bias analysis and reporting.
Table 1: Characteristics of included studies
Study ID
|
Country
|
Study design
|
Objectives
|
Description of the intervention
|
Outcome
|
Geller 2014
|
Ghana
|
Facility-based study: before and after intervention comparison
|
To assess whether community distribution of misoprostol was safe and acceptable
To assess whether community distribution of misoprostol was feasible to prevent postpartum hemorrhage if deliveries occur outside health facilities
|
- Midwives provided misoprostol to expecting women who came for antenatal care during third trimester
- Midwives, nurses, community health workers (CHWs), and the study team were trained to deliver educational messages to
women, with pictorial flip charts explaining drug safety and administration;
- Community sensitization activities regarding safe motherhood,
the importance of skilled delivery,
and safe storage and use of the drug;
- Home visits to pregnant women
by CHWs and other members of the study team further emphasized educational messages
|
- Misuse of misoprostol was not reported in the study
- Misoprostol distribution was not found to encourage home deliveries in rural Ghana
- Household surveys showed that deliveries with skilled providers increased from 30 to 69%.
|
Haver 2016
|
Afghanistan
|
Pre- and post-intervention household surveys in 20 districts
|
To assess whether or not third-trimester distribution of misoprostol would result in adverse events related to child delivery
|
- CHWs educated and counseled community to raise their awareness on misoprostol
- CHWs involved influential people and councils in awareness-raising activities
- Misoprostol was distributed to pregnant women in advance during antenatal care
- The study/ project provided support to health facilities to carry out clean and safe delivery
|
- Uterotonic coverage in the community increased by 24% points after intervention
- Only 1 woman (out of 7,399) reported taking misoprostol before prescribed time (the birth of her newborn)
- Misoprostol distribution did not result in any maternal death
- The proportion of women who gave birth in a facility increased from 50.2% to 60.8% before and after intervention respectively
|
Rajbhandari 2010
|
Nepal
|
Before- and after-intervention household survey
|
- To assess whether advance distribution of misoprostol at community reduces (prevents) PPH occurrence and maternal mortality
|
- Identified and trained community volunteers to distribute misoprostol at community level
- Volunteers educated and counseled pregnant women on prenatal care
- Volunteers made home visits to pregnant women and distributed misoprostol at term
- Volunteers made postnatal home visits and checked use of misoprostol and any adverse outcomes.
|
- The proportion of women who had a vaginal delivery who took misoprostol after delivery rose from 11.6% before intervention to 74.2% after intervention
- The proportion of women who delivered in a health facility increased from 10.9% at baseline to 14.8% at end line
|
Sanghvi 2010
|
Afghanistan
|
Community-based: Non-randomized control trial
|
- To assess whether community distribution of misoprostol was safe and acceptable
- To assess whether community distribution of misoprostol was effective and feasible to prevent postpartum hemorrhage
|
- CHWs made 3 home visits to pregnant women in control and intervention locations
- CHWs educated women and support groups in the family on birth preparedness, PPH, facility delivery and postnatal care
In addition, in intervention areas
- CHWs oriented women and support groups in the family on misoprostol use for PPH prevention and its correct use
- CHWs provided misoprostol and visual aids to women after orientation
- CHWs made postnatal visits at the woman’s house and check use of misoprostol
|
- All women in the intervention areas took misoprostol correctly
- Uterotonic coverage in the intervention areas increased to 92% while it was 25% in control group
- Adverse outcomes were lower in intervention group
- 92% of women in the intervention group said they would use misoprostol in the future
- A statistically significant difference in the proportion of women delivering in a health facility reported i.e. 21% among intervention group and 18% among control group (p<0.001).
|
Weeks 2015
|
Uganda, Mbale District
|
Community-based study: placebo-controlled randomized trial
|
To assess whether self-administration of misoprostol by pregnant women at home was safe and effective
|
- Women were randomly allocated to either intervention or control group
- Women’s hemoglobin level was measured before intervention was provided
- Intervention group received misoprostol 600mcg while control groups were provided placebo
- Women were counseled on how to use the tablets and provided with the tablets to take at home after birth if birth happens at home
- Women’s hemoglobin level was measured on 5th day after delivery
|
- Only 2 women self-administered the intervention before delivery despite they were told not to do so
- More women had experienced shivering and fever among women who took misoprostol compared to placebo group (p>0.05)
- Facility delivery: 56.5% in the misoprostol group vs 58.2% in the placebo group (p>0.05)
|
Smith 2014
|
Liberia
|
Longitudinal observational
study
|
To evaluate whether antenatal distribution of misoprostol was feasible, safe and effective for PPH prevention
|
- Trained traditional midwives were trained as CHWs to educate and women on misoprostol use
- CHWS distributed misoprostol at home
- Misoprostol use was assessed at home after delivery
|
- Only 3(1.1%) women took misoprostol before delivery
- Routine data showed that facility delivery increased from 82 during the comparison period (same period in the previous year) to 108 during the intervention period
|
Ononge 2015
|
Uganda
|
Cluster RCT
|
- To assess whether misoprostol distribution to pregnant women to administer at home (if she decided to deliver at home) during antenatal care reduces PPH
|
- Women were offered misoprostol at 28+ weeks of gestation during antenatal care
- They were counseled on how to take misoprostol if they delivered at home
|
- Taking misoprostol before delivery was not reported.
- Misoprostol use did not affect postpartum anemia, uterotonic use
- Misoprostol use did not affect facility births (85.4% Intervention group vs 87.5 % in Control group)
|
Durham 2018
|
Lao People’s Democratic Republic
|
Qualitative study
|
- To explore contextual factors that were linked to acceptability misoprostol and whether there was a need to distribute misoprostol at community level for prevention of PPH
|
- No intervention was done
- Interviews were conducted with stakeholders at different levels
|
All informants stressed on the need for recognized that community distribution of misoprostol as a solution to reduce PPH
|
Spangler et al 2014
|
Ethiopia
|
Qualitative study
|
- To assess decision-makers’ understanding of Ethiopia’s health policy with regard to community-based use of misoprostol for PPH prevention
|
NA
|
- Decision-makers had different views and lacked clarity on national policy for community-based distribution of misoprostol for PPH prevention.
|
Wells et al 2016
|
Ethiopia, Ghana,
|
Desk review and qualitative methods
|
- To assess what models existed and implemented to ensure access to misoprostol at community
level in Ethiopia, Ghana,
and Nigeria
|
NA
|
- Care providers’ and decision-makers’ lacked trust in women’s ability to use misoprostol correctly
- Care providers’ and decision-makers’ believed that women might use misoprostol pills for abortion
- Care providers and decision-makers feared that women might “misuse” misoprostol before delivery
- Care providers and decision-makers feared that providers inappropriately might use misoprostol for labor induction and/or abortion
|
Sibley 2014
|
Ethiopia
|
Household survey and record reviews
|
- To assess misoprostol use over a period of time
- To assess women’s awareness and use of misoprostol and factors associated with its use (before and after a project)
|
- Trained community health development agents to hold meetings with pregnant women and their caregivers at home.
- Community health development agents educated women and distributed misoprostol tablets in the intervention areas i.e. through HEWs (in Amhara) and TBAs (in Oromia)
|
- Receipt of misoprostol during pregnancy did not affect place of delivery (OR= 0.64; 95% CI, 0.35-1.19, p>0.05).
- Very few women took misoprostol before delivery (~2%)
|
Rajbhandari 2017
|
Nepal
|
Mixed methods program evaluation
|
- To assess whether distribution of misoprostol during antenatal care during a project was effective or not
|
- No intervention
- Household interviews with women who had given birth in the last 12 months in different geographic locations
|
- Increased awareness of misoprostol use for PPH prevention among women
- 96% of community health volunteers said they provided misoprostol to prevent PPH
- Misoprostol use did not decrease institutional delivery;
- No report that misoprostol was used for any other purpose (including labor induction and abortion).
- The majority of those who did not use their advance misoprostol returned it after the birth and most others either threw it away or kept it.
|
Parashar 2018
|
India
|
Cross-sectional program evaluation
|
- To develop a framework to assist with designing and implementing community-based distribution of misoprostol
|
- Pregnant women were more likely to deliver at home (based on criteria) were provided with misoprostol in the 8th month of pregnancy
- Pregnant women were counseled about how to use misoprostol if they delivered at home
|
- Facility delivery increased from 11% to 57% within six months of implementation
|
Derman 2006
|
India
|
RCT
|
- To assess whether oral misoprostol could be an alternative drug to oxytocin for PPH prevention
|
- Auxiliary nurse midwives were trained for 5 days on implementation protocol; attended deliveries; and followed mothers and their newborns postpartum for 6 weeks.
- Midwives attended deliveries and administered misoprostol in intervention group and placebo in control group and measured blood loss
|
- PPH significantly decreased among women who took misoprostol compared to placebo (p<0.001)
- Women who took misoprostol were less likely to need referral for emergency care at another hospital (p<0.05)
- Women who took misoprostol has higher chance of having transient shivering (p<0.05)
- The chance of having nausea, vomiting or diarrhea did not increase due to misoprostol (p>0.05)
|
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 quasi-experimental trials, and one qualitative study) reported on the impact on facility birth as the outcome [38, 39, 37, 36, 41, 35, 43-46]. All five before-after household surveys reported increased facility delivery coverage after the intervention: four percentage points increase in Nepal [39] and Liberia [38], 11% points in Afghanistan [37], 39% points in Ghana [36], and 46% points in India [41] at the end of the intervention when compared to the baseline (Figure 2).
A quasi-experimental study in Afghanistan demonstrated an increase of 3.3 percentage points in facility birth rates comparing between the intervention and control areas (p< 0.001); while a RCT in India showed a decrease of 1.6 percentage points (p>0.05) and two cluster randomized trials in Uganda showed a decrease of 1.5 and 2.1 percentage points (p>0.05) in facility birth rates, comparing between the intervention and control areas [43, 44, 46]. The pooled analysis involving 7,564 women, from four of the studies, revealed that there is no significant difference in facility delivery among the advanced distribution of misoprostol and control groups [OR 1.011; 95% CI: 0.906-1.129] (Table 2).
Table 2: Comparison of facility delivery rates between the intervention and control areas
Study
|
Facility delivery rate (%)
|
OR
|
[95% CI]
|
% Weight
|
Intervention
|
Comparison
|
Sanghvi 2010
|
21.4
|
18.1
|
1.229
|
1.023
|
1.477
|
35.93
|
Weeks 2015
|
56.5
|
58.0
|
0.940
|
0.697
|
1.269
|
13.52
|
Ononge 2015
|
85.4
|
87.5
|
0.834
|
0.647
|
1.075
|
18.80
|
Derman 2006
|
53.2
|
54.8
|
0.937
|
0.770
|
1.139
|
31.76
|
I-V pooled OR
|
|
|
1.011
|
0.906
|
1.129
|
100.0
|
A qualitative study among health professionals in Laos 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 [35]. Another study in Ethiopia reported regional differences in understanding the implementation strategy of misoprostol and concern among policymakers that distribution of misoprostol will be seen as encouraging home birth [26].
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 misused for labor induction or pregnancy termination [42]. 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 [36, 37, 40, 38, 43].
A cluster randomized controlled trial in Uganda [43] and an operations research in Ghana [36] reported that no woman took misoprostol before their babies’ birth. Another before-after study in Afghanistan reported that only 1 out of 7,399 women in the study took misoprostol before the birth of her newborn [37]. Similarly, according to a trial in Uganda, only 2 out of 700 women took tablets before delivery . In Liberia, only 3 of 265 women took misoprostol prior to giving birth [38, 46]; while in Ethiopia, less than 2% of women took the tablets before birth [40] (Table 3).
Table 3: Percent of women who took misoprostol before delivery
Study ID
|
Country
|
%
|
n
|
N
|
Geller 2014
|
Ghana
|
0.00
|
0
|
102
|
Ononge 2015
|
Uganda
|
0.00
|
0
|
2,057
|
Haver 2016
|
Afghanistan
|
0.01
|
1
|
7,399
|
Weeks 2015
|
Uganda
|
0.29
|
2
|
700
|
Smith 2014
|
Liberia
|
1.10
|
3
|
265
|
Sibley 2014
|
Ethiopia
|
1.80
|
11
|
585
|
Total
|
|
|
17
|
11,108
|
Evidence also shows that most women used the misoprostol pills as instructed [39, 36, 44]; unused doses were returned after birth to the point of distribution; and most others either threw it away or kept it [36, 42]. However, qualitative studies in Ethiopia identified, lack of trust in women’s capabilities to use misoprostol correctly [12] and fear of misuse [12, 26], as a problem limiting the expansion of the program.
Adverse effects of misuse
Three studies reported minor adverse effects following misoprostol administration [44, 46, 45]. However, no adverse outcomes of misuse were reported in either of the studies reviewed.