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Healthcare providers experiences of using uterine balloon tamponade (UBT) devices for the treatment of post-partum haemorrhage: A meta-synthesis of qualitative studies
Finlayson K, Vogel JP, Althabe F, Widmer M, Oladapo OT
PloS one. 2021;16(3):e0248656
Abstract
BACKGROUND Postpartum haemorrhage (PPH) is a leading cause of maternal mortality and severe morbidity globally. When PPH cannot be controlled using standard medical treatments, uterine balloon tamponade (UBT) may be used to arrest bleeding. While UBT is used by healthcare providers in hospital settings internationally, their views and experiences have not been systematically explored. The aim of this review is to identify, appraise and synthesize available evidence about the views and experiences of healthcare providers using UBT to treat PPH. METHODS Using a pre-determined search strategy, we searched MEDLINE, CINAHL, PsycINFO, EMBASE, LILACS, AJOL, and reference lists of eligible studies published 1996-2019, reporting qualitative data on the views and experiences of health professionals using UBT to treat PPH. Author findings were extracted and synthesised using techniques derived from thematic synthesis and confidence in the findings was assessed using GRADE-CERQual. RESULTS Out of 89 studies we identified 5 that met our inclusion criteria. The studies were conducted in five low- and middle-income countries (LMICs) in Africa and reported on the use of simple UBT devices for the treatment of PPH. A variety of cadres (including midwives, medical officers and clinical officers) had experience with using UBTs and found them to be effective, convenient, easy to assemble and relatively inexpensive. Providers also suggested regular, hands-on training was necessary to maintain skills and highlighted the importance of community engagement in successful implementation. CONCLUSIONS Providers felt that administration of a simple UBT device offered a practical and cost-effective approach to the treatment of uncontrolled PPH, especially in contexts where uterotonics were ineffective or unavailable or where access to surgery was not possible. The findings are limited by the relatively small number of studies contributing to the review and further research in other contexts is required to address wider acceptability and feasibility issues.
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The cost-effectiveness of tranexamic acid for treatment of postpartum hemorrhage: A systematic review
Aziz S, Rossiter S, Homer CSE, Wilson AN, Comrie-Thomson L, Scott N, Vogel JP
International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics. 2021
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Editor's Choice
Abstract
BACKGROUND Postpartum hemorrhage (PPH) is responsible for nearly one quarter of maternal deaths. A 2017 multicountry trial found that incorporating tranexamic acid (TXA) into the PPH management package was effective in reducing maternal death due to bleeding. OBJECTIVE To systematically review studies assessing the cost-effectiveness of tranexamic acid for PPH treatment. SEARCH STRATEGY Nine databases were searched using variations of keywords 'tranexamic acid', 'postpartum hemorrhage' and 'cost effectiveness'. SELECTION CRITERIA Eligible studies were any type of economic or effectiveness evaluation studies on tranexamic acid for treating women with PPH. DATA COLLECTION AND ANALYSIS Two reviewers independently screened citations and extracted data on cost effectiveness measures. Quality was assessed using the Consensus on Health Economic Criteria list. MAIN RESULTS Four studies were included, of which two were abstracts. Three studies concluded that early administration of TXA was cost-saving or cost-effective. One abstract reported TXA was not cost-effective in the USA unless the probability of death due to hemorrhage is higher. CONCLUSION Available evidence (four studies in three countries) suggests that this life-saving intervention may be below willingness to pay thresholds (cost-effective) or cost saving. Further studies conducted in different populations and settings are needed to inform health policy decision-making to reduce PPH-associated morbidity and mortality.
PICO Summary
Population
Women with post-partum haemorrhage (PPH), (4 studies).
Intervention
Systematic review assessing the cost-effectiveness of tranexamic acid (TXA) for PPH treatment.
Comparison
Outcome
Three studies concluded that early administration of TXA was cost-saving or cost-effective. One abstract reported TXA was not cost-effective in the USA unless the probability of death due to haemorrhage was higher.
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Intravenous oxytocin dosing regimens for postpartum hemorrhage prevention at cesarean section: a systematic review and meta-analysis
Phung LC, Farrington EK, Connolly M, Wilson AN, Carvalho B, Homer CSE, Vogel JP
American journal of obstetrics and gynecology. 2021
Abstract
OBJECTIVE To synthesize available evidence on intravenous (IV) oxytocin dosing regimens for the prevention of postpartum hemorrhage (PPH) at cesarean section (CS). DATA SOURCES We searched Medline/OVID, Embase, Global Index Medicus, CINAHL, CENTRAL, ClinicalTrials.gov, and ICTRP for eligible studies published until Feb 2020. STUDY ELIGIBILITY CRITERIA We included any randomized or non-randomized study published in peer-reviewed journals that compared at least two different dosing regimens of IV oxytocin for PPH prevention in women undergoing CS. STUDY APPRAISAL AND SYNTHESIS METHODS Two authors independently assessed eligibility, extracted data, and assessed risk of bias. Primary outcome was incidence of PPH ≥ 1000 mL. Other review outcomes included use of additional uterotonics, blood loss, and adverse maternal events. Data were analyzed based on type of IV administration (bolus only, infusion only, bolus plus infusion) and oxytocin dose. Meta-analysis was performed using randomized trials and reported using risk ratios or mean difference with 95% confidence intervals. GRADE was used to rate the certainty of evidence. Findings from dose-finding trials and non-randomized studies were reported narratively. RESULTS Thirty-five studies (7,333 women) met our inclusion criteria, including 30 randomized trials and five non-randomized studies. There were limited data from trials for most outcomes, and results were not conclusive. Compared to bolus plus infusion regimens, bolus only regimens probably result in slightly higher mean blood loss (MD 52 mL, 95% CI 0.4-104 mL, moderate certainty). Amongst bolus plus infusion regimens, initial bolus doses < 5 IU may reduce nausea (RR 0.26, 95% CI 0.11-0.63, low certainty) as compared to 5-9 IU. Total oxytocin doses 5-9 IU versus 10-19 IU may increase use of additional uterotonics (RR 13.00, 95% CI 1.75-96.37, low certainty). Effects on other outcomes were generally inconclusive. CONCLUSION There are limited data comparing IV oxytocin regimens for PPH prevention at CS. Bolus plus infusion regimens may lead to minor reductions in mean blood loss, and initial bolus doses of < 5 IU may minimize nausea. Bolus only regimens of 10 IU versus 5 IU may decrease use of additional uterotonics, however further comparative trials are required to understand effects on other key outcomes, particularly hypotension.
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Cost-effectiveness of uterine tamponade devices for the treatment of postpartum haemorrhage: A systematic review
Vogel JP, Wilson AN, Scott N, Widmer M, Althabe F, Oladapo OT
International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics. 2020
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Abstract
BACKGROUND Uterine tamponade is widely promoted for treating refractory postpartum haemorrhage (PPH), however its cost-effectiveness may vary depending on unit costs and setting. OBJECTIVE To review available data on cost-effectiveness of uterine tamponade devices when used for PPH treatment. SEARCH STRATEGY PubMed and EMBASE were searched (1980 to January 2020), as well as the National Health Services Economic Evaluation database from inception (1995) to March 2015. SELECTION CRITERIA Eligible studies were any type of economic evaluation, or effectiveness studies that provided cost or economic data. DATA COLLECTION AND ANALYSIS Two reviewers independently screened studies, extracted data and assessed quality. MAIN RESULTS Eleven studies using a range of devices (condom catheter, uterine suction devices, Bakri, Inpress, Ellavi) were identified. Cost of condom catheter devices or kits ranged from US$0.64 to US$6, while purpose-designed devices were up to US$400. Two studies that took a health system perspective assessed cost-effectiveness of using uterine balloon tamponade and suggested it was highly cost-effective due to low cost per disability-adjusted life years (DALY) averted, though both used effect estimates from case series. CONCLUSIONS Evidence on the cost-effectiveness of uterine tamponade devices was limited and not generalizable. Rigorous economic evaluations based on updated effect estimates are needed.
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Uterotonic agents for first-line treatment of postpartum haemorrhage: a network meta-analysis
Parry Smith WR, Papadopoulou A, Thomas E, Tobias A, Price MJ, Meher S, Alfirevic Z, Weeks AD, Hofmeyr GJ, Gülmezoglu AM, et al
The Cochrane database of systematic reviews. 2020;11:Cd012754
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Editor's Choice
Abstract
BACKGROUND Postpartum haemorrhage (PPH), defined as a blood loss of 500 mL or more after birth, is the leading cause of maternal death worldwide. The World Health Organization (WHO) recommends that all women giving birth should receive a prophylactic uterotonic agent. Despite the routine administration of a uterotonic agent for prevention, PPH remains a common complication causing one-quarter of all maternal deaths globally. When prevention fails and PPH occurs, further administration of uterotonic agents as 'first-line' treatment is recommended. However, there is uncertainty about which uterotonic agent is best for the 'first-line' treatment of PPH. OBJECTIVES To identify the most effective uterotonic agent(s) with the least side-effects for PPH treatment, and generate a meaningful ranking among all available agents according to their relative effectiveness and side-effect profile. SEARCH METHODS We searched the Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (5 May 2020), and the reference lists of all retrieved studies. SELECTION CRITERIA All randomised controlled trials or cluster-randomised trials comparing the effectiveness and safety of uterotonic agents with other uterotonic agents for the treatment of PPH were eligible for inclusion. DATA COLLECTION AND ANALYSIS Two review authors independently assessed all trials for inclusion, extracted data and assessed each trial for risk of bias. Our primary outcomes were additional blood loss of 500 mL or more after recruitment to the trial until cessation of active bleeding and the composite outcome of maternal death or severe morbidity. Secondary outcomes included blood loss-related outcomes, morbidity outcomes, and patient-reported outcomes. We performed pairwise meta-analyses and indirect comparisons, where possible, but due to the limited number of included studies, we were unable to conduct the planned network meta-analysis. We used the GRADE approach to assess the certainty of evidence. MAIN RESULTS Seven trials, involving 3738 women in 10 countries, were included in this review. All trials were conducted in hospital settings. Randomised women gave birth vaginally, except in one small trial, where women gave birth either vaginally or by caesarean section. Across the seven trials (14 trial arms) the following agents were used: six trial arms used oxytocin alone; four trial arms used misoprostol plus oxytocin; three trial arms used misoprostol; one trial arm used Syntometrine® (oxytocin and ergometrine fixed-dose combination) plus oxytocin infusion. Pairwise meta-analysis of two trials (1787 participants), suggests that misoprostol, as first-line treatment uterotonic agent, probably increases the risk of blood transfusion (risk ratio (RR) 1.47, 95% confidence interval (CI) 1.02 to 2.14, moderate-certainty) compared with oxytocin. Low-certainty evidence suggests that misoprostol administration may increase the incidence of additional blood loss of 1000 mL or more (RR 2.57, 95% CI 1.00 to 6.64). The data comparing misoprostol with oxytocin is imprecise, with a wide range of treatment effects for the additional blood loss of 500 mL or more (RR 1.66, 95% CI 0.69 to 4.02, low-certainty), maternal death or severe morbidity (RR 1.98, 95% CI 0.36 to 10.72, low-certainty, based on one study n = 809 participants, as the second study had zero events), and the use of additional uterotonics (RR 1.30, 95% CI 0.57 to 2.94, low-certainty). The risk of side-effects may be increased with the use of misoprostol compared with oxytocin: vomiting (2 trials, 1787 participants, RR 2.47, 95% CI 1.37 to 4.47, high-certainty) and fever (2 trials, 1787 participants, RR 3.43, 95% CI 0.65 to 18.18, low-certainty). According to pairwise meta-analysis of four trials (1881 participants) generating high-certainty evidence, misoprostol plus oxytocin makes little or no difference to the use of additional uterotonics (RR 0.99, 95% CI 0.94 to 1.05) and to blood transfusion (RR 0.95, 95% CI 0.77 to 1.17) compared with oxytocin. We cannot rule out an important benefit of using the misoprostol plus oxytocin combination over oxytocin alone, for additional blood loss of 500 mL or more (RR 0.84, 95% CI 0.66 to 1.06, moderate-certainty). We also cannot rule out important benefits or harms for additional blood loss of 1000 mL or more (RR 0.76, 95% CI 0.43 to 1.34, moderate-certainty, 3 trials, 1814 participants, one study reported zero events), and maternal mortality or severe morbidity (RR 1.09, 95% CI 0.35 to 3.39, moderate-certainty). Misoprostol plus oxytocin increases the incidence of fever (4 trials, 1866 participants, RR 3.07, 95% CI 2.62 to 3.61, high-certainty), and vomiting (2 trials, 1482 participants, RR 1.85, 95% CI 1.16 to 2.95, high-certainty) compared with oxytocin alone. For all outcomes of interest, the available evidence on the misoprostol versus Syntometrine® plus oxytocin combination was of very low-certainty and these effects remain unclear. Although network meta-analysis was not performed, we were able to compare the misoprostol plus oxytocin combination with misoprostol alone through the common comparator of oxytocin. This indirect comparison suggests that the misoprostol plus oxytocin combination probably reduces the risk of blood transfusion (RR 0.65, 95% CI 0.42 to 0.99, moderate-certainty) and may reduce the risk of additional blood loss of 1000 mL or more (RR 0.30, 95% CI 0.10 to 0.89, low-certainty) compared with misoprostol alone. The combination makes little or no difference to vomiting (RR 0.75, 95% CI 0.35 to 1.59, high-certainty) compared with misoprostol alone. Misoprostol plus oxytocin compared to misoprostol alone are compatible with a wide range of treatment effects for additional blood loss of 500 mL or more (RR 0.51, 95% CI 0.20 to 1.26, low-certainty), maternal mortality or severe morbidity (RR 0.55, 95% CI 0.07 to 4.24, low-certainty), use of additional uterotonics (RR 0.76, 95% CI 0.33 to 1.73, low-certainty), and fever (RR 0.90, 95% CI 0.17 to 4.77, low-certainty). AUTHORS' CONCLUSIONS The available evidence suggests that oxytocin used as first-line treatment of PPH probably is more effective than misoprostol with less side-effects. Adding misoprostol to the conventional treatment of oxytocin probably makes little or no difference to effectiveness outcomes, and is also associated with more side-effects. The evidence for most uterotonic agents used as first-line treatment of PPH is limited, with no evidence found for commonly used agents, such as injectable prostaglandins, ergometrine, and Syntometrine®.
PICO Summary
Population
Women with postpartum haemorrhage (PPH), (7 studies, n= 3,738).
Intervention
Systematic review and network meta-analysis identifying the most effective uterotonic agent(s) for first-line PPH treatment with the least side-effects.
Comparison
Oxytocin alone; misoprostol plus oxytocin; misoprostol alone; and Syntometrine® (oxytocin and ergometrine fixed-dose combination) plus oxytocin infusion.
Outcome
Pairwise meta-analysis of two trials (n= 1,787), suggested that misoprostol, as first-line treatment uterotonic agent, probably increases the risk of blood transfusion compared with oxytocin. Low-certainty evidence suggested that misoprostol administration may increase the incidence of additional blood loss of 1,000 mL or more. The data comparing misoprostol with oxytocin was imprecise, with a wide range of treatment effects for the additional blood loss of 500 mL or more, maternal death or severe morbidity. The risk of side-effects may be increased with the use of misoprostol compared with oxytocin. According to pairwise meta-analysis of four trials (n= 1,881 participants) generating high-certainty evidence, misoprostol plus oxytocin made little or no difference to the use of additional uterotonics and to blood transfusion compared with oxytocin.
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What matters to women and healthcare providers in relation to interventions for the prevention of postpartum haemorrhage: A qualitative systematic review
Finlayson K, Downe S, Vogel JP, Oladapo OT
PloS one. 2019;14(5):e0215919
Abstract
BACKGROUND Postpartum haemorrhage (PPH) is a leading cause of maternal mortality and morbidity. Reducing deaths from PPH is a global challenge. The voices of women and healthcare providers have been missing from the debate around best practices for PPH prevention. The aim of this review was to identify, appraise and synthesize available evidence about the views and experiences of women and healthcare providers on interventions to prevent PPH. METHODS We searched eight electronic databases and reference lists of eligible studies published between 1996 and 2018, reporting qualitative data on views and experiences of PPH in general, and of any specific preventative intervention(s). Authors' findings were extracted and synthesised using meta-ethnographic techniques. Confidence in the quality, coherence, relevance and adequacy of data underpinning the resulting themes was assessed using GRADE-CERQual. A line of argument synthesis was developed. RESULTS Thirty-five studies from 29 countries met our inclusion criteria. Our results indicate that women and healthcare providers recognise the dangers of severe blood loss in the perinatal and postpartum period, but don't always share the same beliefs about the causes and consequences of PPH. Skilled birth attendants and traditional birth attendants (TBA's) want to prevent PPH but may lack the required resources and training. Women generally appreciate PPH prevention strategies, especially where their individual needs, beliefs and values are taken into account. Women and healthcare providers also recognize the value of using uterotonics (medications that contract the uterus) to prevent PPH but highlight safety concerns and potential misuse of the drugs as acceptability and implementation issues. CONCLUSIONS Based on stakeholder views and experiences, PPH prevention strategies are more likely to be successful where all stakeholders agree on the causes and consequences of severe postpartum blood loss, especially in the context of sufficient resources and effective implementation by competent, suitably trained providers.
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A systematic review of the cost-effectiveness of uterotonic agents for the prevention of postpartum hemorrhage
Lawrie TA, Rogozinska E, Sobiesuo P, Vogel JP, Ternent L, Oladapo OT
International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics. 2019
Abstract
BACKGROUND Several uterotonic options exist for prevention of postpartum hemorrhage (PPH); hence, cost-effectiveness is an important decision-making criterion affecting uterotonic choice. OBJECTIVE To conduct a systematic review of cost-effectiveness of uterotonics for PPH prevention to support a WHO guideline update. SEARCH STRATEGY We searched major databases from 1980 to June 2018 and the National Health Services Economic Evaluation (NHS EED) database from inception (1995) to March 2015 for eligible studies. SELECTION CRITERIA We included comparative economic evaluations, cost-utility analyses, and resource-utilization studies. DATA COLLECTION AND ANALYSIS Two reviewers independently assessed studies and extracted data organized by birth mode and setting. MAIN RESULTS We included 15 studies across all income categories that compared misoprostol versus no uterotonic (five studies) or versus oxytocin (one study), carbetocin versus oxytocin (eight studies), and one study comparing numerous uterotonics. In specific low-resource contexts, we found reasonably good evidence that misoprostol was cost-effective compared with no uterotonic. In the context of cesarean delivery, carbetocin was more cost favorable than oxytocin but certainty of this evidence was low. CONCLUSIONS Evidence on the cost-effectiveness of various uterotonic agents was not generalizable. As the number of competing uterotonics increases, rigorous economic evaluations including contextual factors are needed. This article is protected by copyright. All rights reserved.
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Uterotonic agents for preventing postpartum haemorrhage: a network meta-analysis
Gallos ID, Papadopoulou A, Man R, Athanasopoulos N, Tobias A, Price MJ, Williams MJ, Diaz V, Pasquale J, Chamillard M, et al
The Cochrane database of systematic reviews. 2018;12:Cd011689
Abstract
BACKGROUND Postpartum haemorrhage (PPH) is the leading cause of maternal mortality worldwide. Prophylactic uterotonic agents can prevent PPH, and are routinely recommended. The current World Health Organization (WHO) recommendation for preventing PPH is 10 IU (international units) of intramuscular or intravenous oxytocin. There are several uterotonic agents for preventing PPH but there is still uncertainty about which agent is most effective with the least side effects. This is an update of a Cochrane Review which was first published in April 2018 and was updated to incorporate results from a recent large WHO trial. OBJECTIVES To identify the most effective uterotonic agent(s) to prevent PPH with the least side effects, and generate a ranking according to their effectiveness and side-effect profile. SEARCH METHODS We searched the Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (24 May 2018), and reference lists of retrieved studies. SELECTION CRITERIA All randomised controlled trials or cluster-randomised trials comparing the effectiveness and side effects of uterotonic agents with other uterotonic agents, placebo or no treatment for preventing PPH were eligible for inclusion. Quasi-randomised trials were excluded. Randomised trials published only as abstracts were eligible if sufficient information could be retrieved. DATA COLLECTION AND ANALYSIS At least three review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. We estimated the relative effects and rankings for preventing PPH ≥ 500 mL and PPH ≥ 1000 mL as primary outcomes. Secondary outcomes included blood loss and related outcomes, morbidity outcomes, maternal well-being and satisfaction and side effects. Primary outcomes were also reported for pre-specified subgroups, stratifying by mode of birth, prior risk of PPH, healthcare setting, dosage, regimen and route of administration. We performed pairwise meta-analyses and network meta-analysis to determine the relative effects and rankings of all available agents. MAIN RESULTS The network meta-analysis included 196 trials (135,559 women) involving seven uterotonic agents and placebo or no treatment, conducted across 53 countries (including high-, middle- and low-income countries). Most trials were performed in a hospital setting (187/196, 95.4%) with women undergoing a vaginal birth (71.5%, 140/196).Relative effects from the network meta-analysis suggested that all agents were effective for preventing PPH ≥ 500 mL when compared with placebo or no treatment. The three highest ranked uterotonic agents for prevention of PPH ≥ 500 mL were ergometrine plus oxytocin combination, misoprostol plus oxytocin combination and carbetocin. There is evidence that ergometrine plus oxytocin (RR 0.70, 95% CI 0.59 to 0.84, moderate certainty), carbetocin (RR 0.72, 95% CI 0.56 to 0.93, moderate certainty) and misoprostol plus oxytocin (RR 0.70, 95% CI 0.58 to 0.86, low certainty) may reduce PPH ≥ 500 mL compared with oxytocin. Low-certainty evidence suggests that misoprostol, injectable prostaglandins, and ergometrine may make little or no difference to this outcome compared with oxytocin.All agents except ergometrine and injectable prostaglandins were effective for preventing PPH ≥ 1000 mL when compared with placebo or no treatment. High-certainty evidence suggests that ergometrine plus oxytocin (RR 0.83, 95% CI 0.66 to 1.03) and misoprostol plus oxytocin (RR 0.88, 95% CI 0.70 to 1.11) make little or no difference in the outcome of PPH ≥ 1000 mL compared with oxytocin. Low-certainty evidence suggests that ergometrine may make little or no difference to this outcome compared with oxytocin meanwhile the evidence on carbetocin was of very low certainty. High-certainty evidence suggests that misoprostol is less effective in preventing PPH ≥ 1000 mL when compared with oxytocin (RR 1.19, 95% CI 1.01 to 1.42). Despite the comparable relative treatment effects between all uterotonics (except misoprostol) and oxytocin, ergometrine plus oxytocin, misoprostol plus oxytocin combinations and carbetocin were the highest ranked agents for PPH ≥ 1000 mL.Misoprostol plus oxytocin reduces the use of additional uterotonics (RR 0.56, 95% CI 0.42 to 0.73, high certainty) and probably also reduces the risk of blood transfusion (RR 0.51, 95% CI 0.37 to 0.70, moderate certainty) when compared with oxytocin. Carbetocin, injectable prostaglandins and ergometrine plus oxytocin may also reduce the use of additional uterotonics but the certainty of the evidence is low. No meaningful differences could be detected between all agents for maternal deaths or severe morbidity as these outcomes were rare in the included randomised trials where they were reported.The two combination regimens were associated with important side effects. When compared with oxytocin, misoprostol plus oxytocin combination increases the likelihood of vomiting (RR 2.11, 95% CI 1.39 to 3.18, high certainty) and fever (RR 3.14, 95% CI 2.20 to 4.49, moderate certainty). Ergometrine plus oxytocin increases the likelihood of vomiting (RR 2.93, 95% CI 2.08 to 4.13, moderate certainty) and may make little or no difference to the risk of hypertension, however absolute effects varied considerably and the certainty of the evidence was low for this outcome.Subgroup analyses did not reveal important subgroup differences by mode of birth (caesarean versus vaginal birth), setting (hospital versus community), risk of PPH (high versus low risk for PPH), dose of misoprostol (≥ 600 mcg versus < 600 mcg) and regimen of oxytocin (bolus versus bolus plus infusion versus infusion only). AUTHORS' CONCLUSIONS All agents were generally effective for preventing PPH when compared with placebo or no treatment. Ergometrine plus oxytocin combination, carbetocin, and misoprostol plus oxytocin combination may have some additional desirable effects compared with the current standard oxytocin. The two combination regimens, however, are associated with significant side effects. Carbetocin may be more effective than oxytocin for some outcomes without an increase in side effects.