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 [33, 25, 12], seven observational studies [34-40], and four experimental or quasi-experimental studies [41-44] were included in this review. All studies were published from 2006 to 2018.
Methodological quality of included studies
According to the JBI quality appraisal tool, two of the Randomized Controlled Trials (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
|
Before-after intervention and comparison facility-based study
|
Assess the safety, feasibility,
and acceptability of community-based distribution of misoprostol
to prevent PPH during home deliveries in rural areas
|
Misoprostol distributed to midwives at seven primary health centers for provision to
pregnant women
|
· No evidence of misuse;
· Misoprostol distribution did not encourage home deliveries;
· Regional household surveys showed that deliveries with skilled providers increased from 30 to 69%.
|
Haver 2016
|
Afghanistan
|
before-and-after cross-sectional household surveys
|
To determine the effectiveness of advance distribution of misoprostol
for self-administration across 20 districts and identify any adverse events that occurred during expansion
|
Community health workers (CHWs) did advance distribution of misoprostol
Interventions: 1) CHWs visited households; 2) community health councils were engaged to raise awareness of misoprostol for prevention of postpartum hemorrhage, and 3) health facility intrapartum services
|
· 1 out of 7,399 women in the study reported taking misoprostol before the birth of her newborn
· No maternal deaths attributable to misoprostol
· Increased proportion of women who gave birth in a facility after the intervention (from 50.2% to 60.8%); the intervention did not discourage women from receiving skilled birth attendance
|
Rajbhandari 2010
|
Nepal
|
Before-after household survey
|
To determine feasibility of community-based distribution of misoprostol (for preventing PPH) to pregnant woman, through community volunteers
|
Support and training to peripheral health workers and female community volunteers to enable them to: identify pregnant women in their area, provide prenatal health education, dispense misoprostol late in pregnancy, and make early postnatal home visits
|
The institutional delivery rate among live births increased from 10.9% at baseline to 14.8% at end line
|
Sanghvi 2010
|
Afghanistan
|
Non-randomized experimental control design
|
To test the safety, acceptability, feasibility, and effectiveness of community-based education and distribution of misoprostol for prevention of postpartum hemorrhage during home birth
|
In both the intervention and comparison areas, CHWs made 3 home visits to pregnant women and their families: CHWs used pictorial flipcharts to provide education on birth preparedness and complication readiness, and recognition of danger signs
|
Significant number of women delivered in facilities (p< 0.001): 21% and 18% of births took place at health facilities in the intervention and comparison areas respectively.
|
Weeks 2015
|
Uganda
|
Community-based placebo-randomized controlled trial (RCT)
|
Examine safety and effectiveness of self-administration of misoprostol by women
|
Women were randomized into misoprostol or placebo group during their third trimester ANC visit and they were instructed to take immediately after childbirth before the delivery of the placenta, and after confirming the absence of a twin, if they delivered at home.
|
Facility delivery: 56.5% in the misoprostol group vs 58.2% in the placebo group
|
Smith 2014
|
Liberia
|
Longitudinal observational
study
|
Evaluate the feasibility, acceptability, effectiveness of advance distribution of misoprostol during ANC and home visits
|
Trained traditional midwives as CHWs provided education to pregnant women, and district reproductive health supervisors distributed misoprostol during home visits
|
Misoprostol taken before delivery of baby; 3 (1.1%)
Based on Health Management Information System data, ANC1 and ANC4 appears to be unchanged, while, the average monthly number of facility deliveries increased from the 82 during the comparison period (same period in the previous year) to 108 during the intervention period
|
Ononge 2015
|
Uganda
|
Cluster RCT
|
To determine if antenatal distribution of misoprostol to pregnant women to self-administer at home birth, reduces PPH
|
Women at 28+ weeks of gestation attending antenatal care were offered misoprostol to swallow immediately after birth of baby when oxytocin was not available
|
· No woman took misoprostol before their baby’s birth.
· No difference in postpartum anemia, uterotonic use, and facility births (85.4% I vs 87.5 % C group)
|
Durham 2018
|
Lao People’s Democratic Republic
|
Qualitative study
IDI, n=25 & FGDs, n=5
|
Identify acceptability of misoprostol and healthcare system needs to effectively distribute misoprostol to women with limited access to facility-based birthing
|
NA
|
All healthcare professionals interviewed recognized that community distribution of misoprostol is an acceptable and feasible interim preventative solution to reduce PPH until access to facility-based birthing is improved
|
Spangler et al 2014
|
Ethiopia
|
Qualitative in-depth interviews
|
The purpose of this study was to examine the understanding of national policy for community-based use of misoprostol to prevent PPH
|
NA
|
Among all officials, understandings of national policy for community-based PPH prevention using misoprostol were unclear.
|
Wells et al 2016
|
Ethiopia, Ghana,
|
Desk review and qualitative methods
|
Evaluated the models and approaches used to access misoprostol at the community
level in Ethiopia, Ghana,
and Nigeria
|
NA
|
· There is pervasive lack of trust in women’s capabilities to use misoprostol correctly and the widely held belief that women might “misuse” the pills (for abortion) persist
· Fears that providers will inappropriately use misoprostol for labor induction and/or abortion
|
Sibley 2014
|
Ethiopia
|
Before-and-after household design; facility records
|
Describes regional trends in women’s use of misoprostol; their awareness, receipt, and use of misoprostol at project’s end line; and factors associated with its use
|
Community health development agents and TBAs conducted community maternal and newborn health family meetings with pregnant women and their family caregivers.
Distributed misoprostol tablets to the project area woreda health offices, to distribute either through HEWs (in Amhara) or TBAs (Oromia)
|
· Controlling for age, parity, and education, region, any ANC, and any CMNH family meeting attendance, a woman’s receipt of misoprostol during pregnancy was not significantly associated with place of birth (OR= 0.64; 95% CI, 0.35-1.19).
· Very few women consumed the tablets before birth (~2%)
|
Rajbhandari 2017
|
Nepal
|
Mixed methods program evaluation
|
This paper presents findings from the first large-scale assessment of the effectiveness of the advance distribution
program.
|
|
· High rate of institutional delivery;
· No evidence 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 design and implement
an operational framework to implement and scale
up “Community Based Advance Distribution of Misoprostol”
program in India
|
Community-based distribution of misoprostol to pregnant women on completion of the 8th month of their pregnancy, in identified high home delivery geographical pockets and women who are likely to deliver at home
|
The institutional delivery rate in the area increased from 11 to 57% within six months of implementation
|
Derman 2006
|
India
|
RCT
|
To investigate whether
oral misoprostol, a potential alternative to oxytocin, could prevent PPH in a community home-birth setting
|
25 auxiliary nurse midwives undertook the deliveries, administered the study drug, and measured blood loss
|
Institutional delivery rate: 53.2% in the intervention group vs 54.8% in comparison group
|
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 [36, 37, 41, 35, 42, 34, 39, 33, 43, 44]. All five before-after household surveys reported increased facility delivery coverage after the intervention: four percentage points increase in Nepal [37] and Liberia [36], 11% points in Afghanistan [35], 39% points in Ghana [34], and 46% points in India [39] 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 [41, 43, 44]. 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 [33]. Another study in Ethiopia reported regional differences in understanding the implementation strategy of misoprostol and a concern among policymakers that distribution of misoprostol will be seen as encouraging home birth [25].
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 [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 [34, 35, 38, 36, 43].
A cluster randomized controlled trial in Uganda [43] and an operations research in Ghana [34] 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 [35]. Similarly, according to a trial in Uganda, only 2 out of 700 women took tablets before delivery [41]. In Liberia, only 3 of 265 women took misoprostol prior to giving birth [36]; while in Ethiopia, less than 2% of women took the tablets before birth [38] (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 [37, 34, 44]; unused doses were returned after birth to the point of distribution; and most others either threw it away or kept it [34, 40]. However, qualitative studies in Ethiopia identified, lack of trust in women’s capabilities to use misoprostol correctly [12] and fear of misuse [12, 25], as a problem limiting the expansion of the program.
Adverse effects of misuse
No adverse outcomes of misuse were reported in either of the studies reviewed.