Effectiveness and safety of misoprostol distributed to antenatal women to prevent postpartum haemorrhage after child-births: a stepped-wedge cluster-randomized trial
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BACKGROUND: Oral misoprostol, administered by trained health-workers is effective and safe for preventing postpartum haemorrhage (PPH). There is interest in expanding administration of misoprostol by non-health workers, including task-shifting to pregnant women themselves. However, the use of misoprostol for preventing PPH in home-births remains controversial, due to the limited evidence to support self-administration or leaving it in the hands of non-health workers. This study aimed to determine if antenatally distributing misoprostol to pregnant women to self-administer at home birth reduces PPH. METHODS: Between February 2013 and March 2014, we conducted a stepped-wedge cluster-randomized trial in six health facilities in Central Uganda. Women at 28+ weeks of gestation attending antenatal care were eligible. Women in the control-arm received the standard-of-care; while the intervention-arm were offered 600 mcg of misoprostol to swallow immediately after birth of baby, when oxytocin was not available. The primary outcome (PPH) was a drop in postpartum maternal haemoglobin (Hb) by ≥ 2 g/dl, lower than the prenatal Hb. Analysis was by intention-to-treat at the cluster level and we used a paired t-tests to assess whether the mean difference between the control and intervention groups was statistically significant. RESULTS: 97% (2466/2545) of eligible women consented to participate; 1430 and 1036 in the control and intervention arms respectively. Two thousand fifty-seven of the participants were successfully followed up and 271 (13.2%) delivered outside a health facility. There was no significant difference between the study group in number of women who received a uterotonic at birth (control 80.4% vs intervention 91.4%, mean difference = -11.0%, 95% confidence interval [CI] -25.7% to 3.6%, p = 0.11). No woman took misoprostol before their baby's birth. Shivering and fever were 14.9% in the control arm compared to 22.2% in the intervention arm (mean difference = -7.2%, 95% CI -11.1% to -3.7%), p = 0.005). There was a slight, but non-significant, reduction in the percentage of women with Hb drop ≥ 2g/dl from 18.5% in the control arm to 11.4% in the intervention arm (mean difference = 7.1%, 95% CI -3.1% to 17.3%, p = 0.14). Similarly, there was no significant difference between the groups in the primary outcome in the women who delivered at home (control 9.6% vs intervention 14.5%, mean difference -4.9; 95% CI -12.7 to 2.9), p = 0.17). CONCLUSION: This study was unable to detect a significant reduction in PPH following the antenatal distribution of misoprostol. The study was registered with Pan-African Clinical Trials Network ( PACTR201303000459148, on 19/11/2012).
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The stepped-wedge design in Ononge et al. 2015 was chosen because current evidence on misoprostol use and postpartum hemorrhage would render a placebo-controlled trial unethical, and all facilities ultimately get the intervention.
“The stepped-wedge design was chosen because current evidence on misoprostol use and postpartum hemorrhage would render a placebo-controlled trial unethical, and all facilities ultimately get the intervention.”
From Applications and implementation considerations for stepped-wedge designs in sub-Saharan Africa: a systematic review (2026) · cites this paper as [96]
The sample size in Ononge et al. 2015 was calculated considering a between-cluster correlation coefficient km = 0.2, a minimum of 200 pregnant women per health facility in each phase, and a proportion experiencing postpartum hemorrhage of 12.0%.
“The sample size was calculated considering a between-cluster correlation coefficient km = 0.2, a minimum of 200 pregnant women per health facility in each phase, and a proportion experiencing postpartum hemorrhage of 12.0%.”
From Applications and implementation considerations for stepped-wedge designs in sub-Saharan Africa: a systematic review (2026) · cites this paper as [96]
The random sequence for starting the intervention in Ononge et al. 2015 was determined using a computer-generated number sequence. The principal investigator implemented the randomization.
“The random sequence for starting the intervention was determined using a computer-generated number sequence. The principal investigator implemented the randomization”
From Applications and implementation considerations for stepped-wedge designs in sub-Saharan Africa: a systematic review (2026) · cites this paper as [96]
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Musa, Z. A., Akinsolu, F. T., Salako, A. O., Abodunrin, O. R., Ola, O. M., & Ezechi, O. C. (2026) · Frontiers in Epidemiology · doi:10.3389/fepid.2026.1529289
- Authors
- Ononge, S., Campbell, O. M. R., Kaharuza, F., Lewis, J. J., Fielding, K., & Mirembe, F.
- Affiliations
- Makerere University (UG)
- London School of Hygiene & Tropical Medicine (GB)
- Corresponding author
- Ononge, Sam
- Venue
- BMC Pregnancy and Childbirth
- Published
- 2015-11-26
- Volume
- 15
- Issue
- 1
- Pages
- 315-315
- ISSN
- 1471-2393 (ISSN-L)
- PMC
- PMC4662032
- OpenAlex
- W2189446016
- Cited by
- 22
- References
- 39
- Citations by year
- 2026: 1 · 2025: 2 · 2023: 2 · 2021: 1 · 2020: 6 · 2019: 2 · 2018: 4 · 2017: 2 · 2016: 1 · 2012: 1
- FWCI
- 2.33
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- BMC Pregnancy and Childbirth (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (acceptedVersion)
- LSHTM Research Online (London School of Hygiene and Tropical Medicine) (acceptedVersion)
- Funders
- Wellcome Trust (087540)
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Maternal and fetal healthcare
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Health and Contraception
- Health Sciences › Medicine › Obstetrics and Gynecology › Maternal and Perinatal Health Interventions
- Keywords
- misoprostol, postpartum hemorrhage, home birth, oxytocin, uterotonic agents, maternal hemoglobin, adverse effects, task shifting, prenatal care, Uganda, resource-limited settings, obstetric care, health workforce shortage
- MeSH terms
- Administration, Oral, Adult, Drug Administration Schedule, Female, Fever, Hemoglobins, Postpartum Hemorrhage, Home Childbirth, Humans, Oxytocics, Pregnancy, Self Administration, Shivering, Uganda, Cluster Analysis, Misoprostol, Delivery, Obstetric, Postpartum Period, Young Adult
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