Excessive bleeding after childbirth, known as postpartum haemorrhage (PPH), can turn an uncomplicated birth into a catastrophe. Each year, PPH occurs in an estimated 27 million women worldwide-17 million after vaginal birth and 10 million during or after caesarean birth. An estimated 43 000 women die from PPH annually, translating to a death every 12 min. The pooled prevalence of PPH at vaginal birth is 12·6% (95% CI 10·1-15·2) and at caesarean birth 30·9% (95% credible interval 24·9-37·6), based on the conventional definition of PPH. Common causes of PPH are uterine atony, genital tract trauma, retained placenta, abnormal placentation, and coagulopathy. Risk factors include caesarean birth, multiple pregnancy, anaemia, high maternal BMI, previous PPH, female genital mutilation, sepsis, pre-eclampsia, macrosomia, and inadequate antenatal care. In addition to being the leading cause of maternal mortality worldwide, the consequences of PPH include serious morbidities such as severe anaemia, hysterectomy, organ failure, and long-term psychological trauma. The global economic burden of PPH is estimated at US$10·4 billion (95% credible interval $9·8-13·2 billion) annually, consisting of $3·6 billion ($3·2-6·2 billion) for health systems and $6·8 billion ($6·2-7·5 billion) for societies. Based on a rigorous review of the evidence, WHO has recently redefined PPH as objectively measured blood loss of at least 300 mL plus an abnormal haemodynamic sign, or objectively measured blood loss of at least 500 mL, whichever occurs first. This new definition prioritises early PPH diagnosis and treatment to avert life-threatening maternal outcomes. Comprehensive efforts to address missed opportunities in the prevention, diagnosis, and treatment of PPH are needed to improve outcomes. These efforts include addressing the unmet need for contraception, mitigating modifiable risks such as anaemia, avoiding caesarean sections that are not medically indicated, using effective single uterotonic prophylaxis for all births and combination prophylaxis for women at high risk of PPH, ensuring accurate and objective measurement of blood loss for early PPH diagnosis, and promptly implementing treatment with an evidence-based bundle. The PPH Roadmap (2023-30) provides a global framework for action.

Abstract Background The World Health Organization develops evidence-based recommendations for postpartum hemorrhage (PPH) prevention, detection, and treatment. However, persistently high PPH-related mortality suggests recommendations are poorly implemented, especially in low-resource settings. This study aimed to identify implementation bottlenecks to inform action. Methods Drawing on public policy, implementation science, and health behavior, we constructed a multi-level framework to identify bottlenecks affecting recommendation uptake. This informed the development of a survey assessing which bottlenecks affected specific WHO recommendations. Surveys were completed by global stakeholders and by health care workers in three high-burden countries. We also analyzed direct observations of clinical practice from those countries to see how bottlenecks affected practice. An a priori interpretive threshold of 75% was selected to indicate a bottleneck was not a severe impediment to implementation. Results Surveys from 102 global stakeholders and 246 health care workers, as well as 2039 direct observations of clinical practice revealed variation in adherence to WHO recommendations, with some through-lines. Oxytocin for PPH prevention and treatment was perceived to have national policy support (> 75% for inclusion in national guidelines and Essential Medicines Lists, regulatory approval, and support from national champions) but other uterotonics were not. Tranexamic acid for PPH treatment was found to be underutilized, likely due to compounding bottlenecks. Respondents reported extensive bottlenecks to refractory PPH interventions (< 75% across nearly all bottlenecks). The most substantial bottlenecks were availability/procurement of medicines and devices, affordability and quality of medicines and devices, presence of job aids, and availability of qualified staff. Observed practice generally aligned with stakeholder perceptions. Conclusions National policy bottlenecks strongly mediated implementation in clinical practice. Policy change addressing gaps in commodity procurement and availability of trained clinicians is critical. Efforts addressing only one part of the implementation ecosystem are unlikely to drive transformative change.

Although commonly used to evaluate health interventions, cluster randomized trials raise difficult ethical issues. Recognizing this, the Ottawa Statement on the Ethical Design and Conduct of Cluster Randomized Trials, published in 2012, provides 15 recommendations to address ethical issues across seven domains. But due to several developments in the design and implementation of cluster randomized trials, there are new issues requiring guidance. To inform the forthcoming update of the Ottawa Statement, we aimed to identify any gaps in the Ottawa Statement discussed within the literature. We searched Google Scholar, Scopus, and Web of Science using the ‘cited by’ function on 11 November 2022.We included all types of publications, including articles, book chapters, commentaries, editorials, ethics guidelines, theses and trial-related publications (i.e., primary reports, protocols, and secondary analyses), that cited and engaged with the Ottawa Statement, the Ottawa Statement précis, or one or more of its four background papers. Data were extracted by four reviewers working in rotating pairs. Reviewers captured relevant text verbatim and recorded whether it reflected a gap relating to one or more of the Ottawa Statement domains. Using a thematic analysis approach, semantic coding was used to summarize the content of the data into distinct gaps within the Ottawa Statement domains, which was subsequently expanded in an inductive manner through discussion. The qualitative analysis of the text from 53 articles resulted in the identification of 24 distinct gaps in the Ottawa Statement: 4 gaps about justifying the cluster randomized design; 2 gaps about research ethics committee review; 3 gaps about identifying research participants; 4 gaps about obtaining informed consent; 3 gaps about gatekepeers; 6 gaps about assessing benefits and harms; 1 gap about protecting vulnerable participants; and 1 gap about equity-related issues in cluster randomized trials. Identifying 24 gaps reveals a need to update the Ottawa Statement. Alongside additional gaps identified in ongoing empirical work and through engagement with our patient and public partners, the gaps identified through this citation analysis should be considered in the forthcoming Ottawa Statement update.

BackgroundPostpartum haemorrhage (PPH) is the leading cause of maternal mortality, particularly in low- and- middle-income countries. The E-MOTIVE trial demonstrated a 60% reduction in severe PPH and related complications with the E-MOTIVE intervention compared to usual care. This nested observational study explored clinical care practices between the time of vaginal birth and the removal of the obstetric drape. Specifically, we assessed the frequency of postpartum maternal assessments, including blood pressure, pulse, uterine tone, vaginal blood flow, and cumulative blood loss assessment—unique to the intervention. We also evaluated diagnostic methods, and blood loss thresholds used for PPH, and how these practices may have contributed to differences in PPH diagnosis and outcomes between E-MOTIVE intervention hospitals and usual care hospitals.MethodsThis prospective observational study, nested within the E-MOTIVE trial, involved passive, direct observations of healthcare workers providing postpartum care to women and managing PPH across 78 hospitals in Nigeria, Kenya, Tanzania, and South Africa. We conducted a descriptive analysis of the frequency and timing of postpartum maternal assessments, diagnostic methods and blood loss thresholds used to diagnose PPH, comparing clinical practices between E-MOTIVE care and usual care.ResultsBetween June and December 2022, the study included 2,578 women at E-MOTIVE care hospitals and 2,834 at usual care hospitals. At E-MOTIVE hospitals, 88% (2,272/2,578) of women received at least one postpartum maternal assessment, 71% (1,825/2,578) at least two, 57% (1,479/2,578) at least three, and 48% (1,234/2,578) four, with assessments conducted earlier and more frequently than at usual care hospitals. Objective blood loss quantification improved diagnosis, with the most common method and blood loss threshold at E-MOTIVE hospitals being ≥300 mL plus at least one abnormal clinical sign, used in 47% (140/295) of PPHs. Postpartum haemorrhage was diagnosed earlier and more frequently at E-MOTIVE hospitals: 76% (223/295) within 30 min, 97% (287/295) within 60 min, and 100% 295/295) within 90 min (median: 17 min; IQR 11–30), compared to 54% (119/219), 79% (173/219), 96% (210/219) respectively, and 100% within 134 min in usual care (median: 26 min; IQR 13–56).DiscussionFrequent and timely postpartum maternal assessments, along with objective blood loss thresholds of with at least one abnormal clinical sign and ≥500 mL may enhance early PPH diagnosis. The first 90 min postpartum has been identified as a critical window for early diagnosis, termed the “Golden 90 min for PPH diagnosis.” Incorporating these insights into clinical training and guidelines may support improved maternal outcomes related to PPH.

OBJECTIVE:To compare the frequency and timing of postpartum haemorrhage (PPH) treatment initiation between hospitals implementing the MOTIVE treatment bundle (which consisted of uterine Massage, Oxytocic drugs, Tranexamic acid, IntraVenous fluids and Examination) and those following usual care. DESIGN:Nested prospective observational study. SETTING:Hospitals in Nigeria, Kenya, Tanzania and South Africa participating in the E-MOTIVE trial. POPULATION OR SAMPLE:Healthcare workers treating PPH. METHODS:Between June and December 2022, we observed healthcare workers for 1-2 weeks in 39 E-MOTIVE and 39 usual care hospitals across Nigeria, Kenya, Tanzania, and South Africa managing vaginal birth and treating PPH. We descriptively compared the frequency and timing from PPH detection to treatment initiation of individual treatments and the MOTIVE bundle, between E-MOTIVE care and usual care. RESULTS:Among 2578 observations in E-MOTIVE care hospitals, 295 (11%) PPHs were treated, and among 2834 observations in usual care hospitals, 219 (8%) PPHs were treated. In E-MOTIVE care hospitals, 97% (286/295) of women with PPH received the MOTIVE bundle, compared to 36% (79/219) in usual care. Median initiation times for the first component were similar (0 vs. 1 min), but E-MOTIVE care hospitals achieved faster initiation of all components (13 min, IQR 6-18) compared to usual care (18 min, IQR 10-25). In total, 79% (233/295) of women in E-MOTIVE care had all components initiated within 20 min, compared to 22% (48/219) in usual care. CONCLUSIONS:Timely and comprehensive management of PPH using the MOTIVE bundle, particularly initiating all components within 15-20 min, was commonly observed in the E-MOTIVE care hospitals. Scaling up E-MOTIVE care should emphasise timely bundle initiation to strengthen PPH treatment and improve maternal health outcomes in low-and-middle-income countries.

IntroductionNearly half of all perinatal deaths occur during the intrapartum period due to inadequate labor monitoring and intervention. The partograph, a paper-based labor monitoring tool, can assist providers in recognizing and acting on early signs of fetal-maternal distress if used effectively. In 2020, the World Health Organization (WHO) developed a "next generation" partograph called the Labour Care Guide. There is limited evidence of how to optimize the use and impact of this new tool. This study describes the development of a co-designed LCG implementation strategy in Karnataka, India.MethodsA targeted literature review, primary research across four public maternity hospitals (provider survey and facility assessment), and a 2-day co-design workshop with stakeholders were conducted. Findings were mapped to six target behaviors using the Theoretical Domains Framework (TDF) and the Capability, Opportunity, and Motivation-Behavior (COM-B) model to identify potential barriers and facilitators to LCG use. Consultations with local stakeholders explored these factors, and a 1-week pilot informed final refinements of the strategy.ResultsThe LCG implementation strategy comprised an evidence-based provider training program centered on "low dose, high frequency" principles, and monthly audit and feedback cycles, which in turn, relies on an enabling practice environment (supportive national policy frameworks, facility-level guidelines, external partnerships, senior support, defining provider roles and expectations and adequate equipment and resources) to support its implementation.ConclusionEffective use of the LCG needs a robust, context-sensitive implementation strategy. We present the first evidence-based, co-designed LCG implementation strategy which can be used to support LCG dissemination and uptake.

Background Postpartum haemorrhage is a leading cause of maternal mortality. A multicountry, cluster-randomised trial (E-MOTIVE) demonstrated a 60% reduction in adverse postpartum haemorrhage outcomes. The E-MOTIVE intervention included early postpartum haemorrhage detection using calibrated blood-collection drapes, followed by a postpartum haemorrhage treatment bundle (ie, uterine massage, oxytocics, tranexamic acid, intravenous fluids, examination and escalation [MOTIVE]), supported by implementation strategies. We report a mixed-methods process evaluation assessing the implementation of the E-MOTIVE intervention in Kenya, Nigeria, South Africa, and Tanzania. Methods In this mixed-methods process evaluation, data sources were observations of health workers providing clinical care to pregnant women and pregnant people during vaginal birth and postpartum haemorrhage at intervention sites, and surveys and qualitative interviews with health workers at intervention and control sites. Intervention sites received the calibrated drapes, MOTIVE bundle, and implementation strategies and control sites used uncalibrated drapes. Primary implementation outcomes included fidelity, adoption, adaptation, acceptability, feasibility, and contamination to the calibrated drape, MOTIVE bundle, and implementation strategies. Findings Between June 1, 2022, and Jan 31, 2023, 2578 births were observed, 295 pregnant women and people had postpartum haemorrhage, 47 qualitative interviews were done, and 889 surveys were completed. Fidelity to calibrated drape use was high (birth observations 2578 [100%] of 2578; survey 451 [983%] of 459). Among health workers, calibrated drape acceptability was high; however, they reported barriers to pregnant women's and people's acceptability. Fidelity to postpartum haemorrhage treatment bundle delivery was high (birth observations 286 [969%] of 295), with moderate to high fidelity in median time from postpartum haemorrhage diagnosis to final treatment initiation (<= 15 min initiation time in 191 [668%] of 295 birth observations, 16-20 min in 42 [147%] birth observations), and high acceptability and feasibility. Research midwives participated in clinical assessments after birth and bundle delivery in some sites (mixed fidelity). Interpretation This process evaluation shows generally high levels of fidelity, feasibility, and acceptability of the calibrated drape and treatment bundle across evaluation methods and countries. The E-MOTIVE intervention should be included in national policies, with consideration for health workforce, supplies, and medication issues, which might need addressing for successful implementation.

BACKGROUND:Postpartum haemorrhage (excessive bleeding after birth) is a leading cause of maternal mortality and morbidity worldwide. However, there is no global consensus on which clinical markers best define excessive bleeding or reliably predict adverse maternal outcomes. The aim of this study was to assess the prognostic accuracy of clinical markers of postpartum bleeding in predicting maternal mortality or severe morbidity. METHODS:In this individual participant data meta-analysis, eligible datasets were identified through a global call for data issued by WHO and systematic searches of PubMed, MEDLINE, Embase, the Cochrane Library, and WHO trial registries (from database inception to Nov 6, 2024). Studies were eligible if they included at least 200 participants with objectively measured blood loss or other clinical markers of haemodynamic instability, and reported at least one clinical outcome of interest. Individual participant data were requested for all eligible studies. For each dataset, we computed the prognostic accuracy of each clinical marker to predict a composite outcome of maternal mortality or severe morbidity (blood transfusion, surgical interventions, or admission to intensive care unit). Five clinical markers were assessed: measured blood loss, pulse rate, systolic blood pressure, diastolic blood pressure, and shock index. Results were meta-analysed through two-level mixed-effects logistic regression models, with a bivariate normal model used to generate summary accuracy estimates. Clinical marker and threshold selections were informed by a WHO expert consensus process, which placed emphasis on maximising prognostic sensitivity (preferably >80%) over prognostic specificity (preferably ≥50%). This meta-analysis was registered on PROSPERO (CRD420251034918). FINDINGS:We identified 33 potentially eligible datasets and successfully obtained and analysed full data for 12 datasets, comprising 312 151 women. At the conventional threshold of 500 mL, measured blood loss had a summary prognostic sensitivity of 75·7% (95% CI 60·3-86·4) and specificity of 81·4% (95% CI 70·7-88·8) for predicting the composite outcome. The preferred sensitivity threshold was reached at 300 mL (83·9% [95% CI 72·8-91·1]), although at the expense of reduced specificity (54·8% [95% CI 38·0-70·5]). Prognostic performance improved with a decision rule that combined the use of either blood loss thresholds less than 500 mL (≥300 mL to ≥450 mL) and any abnormal haemodynamic sign (pulse rate >100 beats per min, systolic blood pressure <100 mm Hg, diastolic blood pressure <60 mm Hg, or shock index >1·0) or 500 mL or more of blood loss, with sensitivities ranging from 86·9% to 87·9% and specificities from 66·6% to 76·1%. INTERPRETATION:Measured blood loss below the conventional threshold, combined with abnormal haemodynamic signs, accurately predicts women at risk of death or life-threatening complications from postpartum bleeding and could support earlier postpartum haemorrhage diagnosis and treatment. FUNDING:The Gates Foundation and UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction.

Background Knowledge translation (KT) approaches have been advocated to increase uptake of evidence to improve maternal health outcomes in low- and middle-income countries (LMICs). However, their use is limited by lack of KT capacity and limited applicability of many existing KT tools to the unique challenges of LMIC health settings. We developed and evaluated a toolkit designed for use by non-experts and tailored to support implementation planning in LMICs.Method Based on our prior research which identified common implementation barriers across five LMICs, a literature review and a qualitative study with women and families in two LMICs, we developed a preliminary item list. Through consultation with our international partners, the item list was refined, a draft toolkit developed and usability tested.Pilot evaluation of the toolkit employed observation and focus groups with participants at implementation planning meetings conducted in Argentina and Ghana, focused on locally identified evidence-based maternal health implementation priorities.Results 31 interested parties participated, 10 in Argentina and 21 in Ghana, representing a range of roles relevant to implementation in the local contexts including providers, health educators, policy/decision makers, researchers and patients/patient representatives. Participants reported a number of benefits to the content and organisation of both the toolkit and meeting format, which they noted encouraged open exchange of perspectives and experiences, and comprehensive consideration and discussion of barriers and facilitators (BFs) to implementation in their context. Minor changes to the instructions and wording of a few BFs were suggested and incorporated.Conclusion The toolkit provides a resource to support LMIC maternal health implementers by offering a structured approach to assessment and ranking of BFs to implementation and a guide to mapping BFs to evidence-based implementation strategies. Further evaluation across a wider range of health topics and LMICs and in low-resource contexts in high-income countries is needed.Study registration Open Science Framework https://osf.io/328dy Registered 31 May 2023.

OBJECTIVES:Cluster randomized trials (CRTs) are frequently used to evaluate interventions in low- and middle-income countries (LMICs). Robust execution and transparent reporting of randomization procedures are essential for successful implementation and accurate interpretation of CRTs. Our objectives were to review the quality of reporting and implementation of randomization procedures in a sample of parallel-arm CRTs conducted in LMICs. STUDY DESIGN AND SETTING:We selected a random sample of 300 primary reports of parallel-arm CRTs from a database of 800 CRTs conducted in LMICs between 2017 and 2022. Data were extracted by two reviewers per trial and summarized using descriptive statistics. RESULTS:Among 300 trials, 192 (64%) reported the method of sequence generation, 213 (71%) reported the type of randomization procedure used, 146 (49%) reported who generated the sequence, 136 (45%) reported whether randomization was implemented by an independent person, and 75 (25%) reported a method of allocation concealment. Among those reporting the methods used, suboptimal randomization procedures were common: 28% did not use a computer, 21% did not use restricted randomization, 58% did not use a statistician to generate the sequence, in 53% the person was not independent from the trial, and 80% did not use central randomization. Public randomization ceremonies were used in 10% of trials as an alternative method of allocation concealment and to reassure participants of fair allocation procedures. CONCLUSION:The conduct and reporting of randomization procedures of CRTs in LMICs is suboptimal. Dissemination of guidance to promote robust implementation of randomization in LMICs is required, and future research on the implementation of public randomization ceremonies is warranted. PLAIN LANGUAGE SUMMARY:Cluster randomized trials (CRTs) are trials where entire groups, rather than individuals, are randomly assigned to different treatments (eg, intervention or usual care). This randomization process can be challenging in CRTs; clear reporting and proper execution are important to ensure fairness and accurate results. In this study, we reviewed how well randomization procedures were reported and carried out in 300 CRTs, selected from a larger database of 800 CRTs, conducted in low- and middle-income countries (LMICs), and published between 2017 and 2022. We found that reporting on key aspects of randomization was often incomplete: 64% reported how they created the random allocation sequence, 71% reported the type of randomization method used, 49% reported who generated the sequence, 45% reported whether a person independent from the trial handled the randomization, and 25% reported how they kept group assignments hidden until the intervention was ready to begin. Even when trials did reported these methods, many did not follow best practices: 28% did not use a computer, 21% did not apply techniques to ensure balanced treatment arms, 58% did not involve a statistician to generate the sequence, 53% had someone involved in the trial handle randomization (as opposed to an independent person), and 80% did not use central randomization to assign groups, where a third party reveals treatment assignment to groups. Interestingly, 10% of trials used public randomization ceremonies (events where group assignments are revealed in a public setting) to keep group assignments hidden until revealment and to reassure participants that the process was fair. Overall, we found that randomization procedures in CRTs were often not well reported or carried out optimally. It is important for researchers to follow established guidelines to ensure randomization is done properly in CRTs in LMICs. More research is also needed to understand how public randomization ceremonies are used in practice.

BACKGROUND:The definition of primary postpartum haemorrhage as blood loss of 500 mL or more within 24 h after vaginal birth underemphasises the early postpartum hours due to limited data on the timing of postpartum haemorrhage diagnosis. Understanding postpartum haemorrhage diagnosis timing and diagnostic methods is important for guiding diagnostic and therapeutic strategies. The E-MOTIVE trial evaluated early postpartum haemorrhage diagnosis and a bundled treatment approach, which resulted in a 60% relative reduction in adverse outcomes from bleeding compared with usual care. We aimed to compare timing from vaginal birth to postpartum haemorrhage diagnosis and the diagnostic methods used among four African countries implementing the intervention from the E-MOTIVE trial. METHODS:Nested within the E-MOTIVE trial (NCT04341662), we conducted direct observations of health-care workers providing clinical care to postpartum women at 39 hospitals implementing the E-MOTIVE intervention across Nigeria, Kenya, Tanzania, and South Africa. One to two weeks of continuous observations were conducted from vaginal birth up to 2 h, between June 27, and Dec 18, 2022. Health-care workers were trained to use clinical judgement (ie, heavy vaginal blood loss, large blood clots expelled, or constant trickle) and various objective blood loss thresholds to diagnose postpartum haemorrhage. The objective blood loss thresholds used in Nigeria, Kenya, and Tanzania were 300 mL or more with at least one abnormal clinical sign (ie, pulse, blood pressure, uterine tone, and vaginal blood flow) or 500 mL or more. The objective blood loss threshold in South Africa was 500 mL or more. We descriptively analysed and compared timing from vaginal birth to postpartum haemorrhage diagnosis and diagnostic methods used between countries. FINDINGS:Of 2578 women, 295 postpartum haemorrhages were diagnosed. The median time from vaginal birth to postpartum haemorrhage diagnosis was 15 min in Nigeria and Tanzania, 17 min in Kenya, and 30 min in South Africa. Diagnosis within 30 min ranged from 58% in South Africa to 86% in Tanzania. By 60 min, 96% to 100% of postpartum haemorrhages were diagnosed across all countries. All postpartum haemorrhages that required an intervention were diagnosed within 90 min. Nigeria, Kenya, and Tanzania commonly used blood loss of 300 mL or more combined with at least one abnormal clinical sign (47%, 65%, and 68%, respectively) while South Africa relied on a definition of 500 mL or more (81%) as the dominant diagnostic strategy. INTERPRETATION:In countries where an objective blood loss threshold of 300 mL or more with at least one abnormal clinical sign was used, women received earlier interventions for postpartum bleeding, with a median time to diagnosis of 15-17 min. This was notably faster than in the country that predominantly used a 500 mL or more threshold, where the median time to diagnosis was 30 min. Regardless of whether the threshold was 300 mL or more with abnormal clinical signs or 500 mL or more alone, all postpartum haemorrhages were diagnosed within 90 min of vaginal birth. FUNDING:Bill & Melinda Gates Foundation and Ammalife.

INTRODUCTION:Postpartum haemorrhage (PPH) remains the leading cause of maternal death. Yet there is a lack of clarity around what research is needed to determine what works and how best to deliver proven PPH interventions. This article describes a WHO-led effort to develop a global PPH research agenda for 2023-2030, to reinvigorate research and innovation while avoiding duplication and waste. METHODS:Potential questions were culled from evidence gaps in a forthcoming Lancet PPH series, a pipeline analysis on PPH medicines and devices, international PPH guidelines, previous research prioritisation efforts and submissions from a reference group of PPH experts and stakeholders. Questions were deduplicated and consolidated, categorised into three tracks (innovation, implementation and cross-cutting) and subjected to an online prioritisation survey. Survey participants (n=120) assessed these questions using five criteria (answerability, effectiveness, deliverability, maximum potential for disease burden reduction and equity) following the Child Health and Nutrition Research Initiative methodology. The outcome of this exercise was complemented by an in-person consensus meeting (Global PPH Summit from 7 March 2023 to 10 March 2023 in Dubai, United Arab Emirates) to finalise the research agenda. RESULTS:Fifteen research questions (five per track) were identified as top priority. The top question per track called for research on the comparative effectiveness and safety of alternative routes of administration (other than the intravenous route) of tranexamic acid in the treatment of PPH (innovation); identifying barriers and facilitators affecting the adoption and use of evidence-based recommendations for PPH management (implementation) and the effectiveness of a strategy of early detection and first response treatment using a bundle of recommended interventions for improving PPH-related outcomes (cross-cutting). CONCLUSION:This shared research agenda should guide future investments into PPH studies with high potential to transform policy and clinical practice in the near term to medium term. Funding for the new research priorities is urgently needed.

Objective There are no globally agreed on strategies on early detection and first response management of postpartum haemorrhage (PPH) during and after caesarean birth. Our study aimed to develop an international expert’s consensus on evidence-based approaches for early detection and obstetric first response management of PPH intraoperatively and postoperatively in caesarean birth.Design Systematic review and three-stage modified Delphi expert consensus.Setting International.Population Panel of 22 global experts in PPH with diverse backgrounds, and gender, professional and geographic balance.Outcome measures Agreement or disagreement on strategies for early detection and first response management of PPH at caesarean birth.Results Experts agreed that the same PPH definition should apply to both vaginal and caesarean birth. For the intraoperative phase, the experts agreed that early detection should be accomplished via quantitative blood loss measurement, complemented by monitoring the woman’s haemodynamic status; and that first response should be triggered once the woman loses at least 500 mL of blood with continued bleeding or when she exhibits clinical signs of haemodynamic instability, whichever occurs first. For the first response, experts agreed on immediate administration of uterotonics and tranexamic acid, examination to determine aetiology and rapid initiation of cause-specific responses. In the postoperative phase, the experts agreed that caesarean birth-related PPH should be detected primarily via frequently monitoring the woman’s haemodynamic status and clinical signs and symptoms of internal bleeding, supplemented by cumulative blood loss assessment performed quantitatively or by visual estimation. Postoperative first response was determined to require an individualised approach.Conclusion These agreed on proposed approaches could help improve the detection of PPH in the intraoperative and postoperative phases of caesarean birth and the first response management of intraoperative PPH. Determining how best to implement these strategies is a critical next step.

ObjectiveCluster randomised trials (CRTs) are used for evaluating health-related interventions in low-income and middle-income countries (LMICs) but raise complex ethical issues. To inform the development of future ethics guidance, we aim to characterise CRTs conducted exclusively in LMICs by examining the types of clusters, settings, author affiliations and primary clinical focus and to evaluate adherence to trial registration and ethics reporting requirements over time.DesignA systematic scoping review using the Preferred Reporting Items for Systematic Review and Meta-Analyses Extension for Scoping Reviews.Data sourcesWe searched MEDLINE between 1 January 2017 and 17 August 2022.Eligibility criteria for selecting studiesWe included primary reports of CRTs evaluating health-related interventions, conducted exclusively in LMICs and published in English between 2017 and 2022.Data extraction and synthesisData were extracted by one reviewer; a second reviewer verified accuracy by extracting data from 10% of the reports. Results were summarised overall and categorised by country’s economic level or publication year.ResultsAmong 800 identified CRTs, 400 (50.0%) randomised geographical areas and 373 (46.6%) were conducted in Africa. 30 (3.7%) had no authors with an LMIC affiliation, and 246 (30.8%) had neither first nor last author with an LMIC affiliation. The relative frequency of first or last authors holding an LMIC affiliation increases as a country’s economic level increases. Most CRTs focused on reducing maternal and neonatal disorders (106, 13.3%). 670 (83.8%) CRTs reported trial registration, 786 (98.2%) reported research ethics committee review and 757 (94.6%) reported consent statements. Among the 757 CRTs, 46 (6.1%) reported a waiver or no consent and, among these, 10 (21.7%) did not provide a rationale. Gatekeepers were identified in 403 (50.4%) CRTs. No meaningful trends were observed in adherence to trial registration or ethics reporting requirements over time.ConclusionOur findings suggest existing inequity in authorship practices. There is high adherence to trial registration and ethics reporting requirements, although greater attention to reporting a justification for using a waiver of consent is needed.

Cesarean section rates worldwide are rising, driven by medically unnecessary cesarean use. The new World Health Organization Labour Care Guide (LCG) aims to improve the quality of care for women during labor and childbirth. Using the LCG might reduce overuse of cesarean; however, its effects have not been evaluated in randomized trials. We conducted a stepped-wedge, cluster-randomized pilot trial in four hospitals in India to evaluate the implementation of an LCG strategy intervention, compared with routine care. We performed this trial to pilot the intervention and obtain preliminary effectiveness data, informing future research. Eligible clusters were four hospitals with >4,000 births annually and cesarean rates ≥30%. Eligible women were those giving birth at ≥20 weeks’ gestation. One hospital transitioned to intervention every 2 months, according to a random sequence. The primary outcome was the cesarean rate among women in Robson Group 1 (that is, those who were nulliparous and gave birth to a singleton, term pregnancy in cephalic presentation and in spontaneous labor). A total of 26,331 participants gave birth. A 5.5% crude absolute reduction in the primary outcome was observed (45.2% versus 39.7%; relative risk 0.85, 95% confidence interval 0.54–1.33). Maternal process-of-care outcomes were not significantly different, though labor augmentation with oxytocin was 18.0% lower with the LCG strategy. No differences were observed for other health outcomes or women’s birth experiences. These findings can guide future definitive effectiveness trials, particularly in settings where urgent reversal of rising cesarean section rates is needed. Clinical Trials Registry India number: CTRI/2021/01/030695 .

Aim To describe standardised iterative methods used by a multidisciplinary group to develop evidence-based clinical intrapartum care algorithms for the management of uneventful and complicated labours. Population Singleton, term pregnancies considered to be at low risk of developing complications at admission to the birthing facility. Setting Health facilities in low- and middle-income countries. Search strategy Literature reviews were conducted to identify standardised methods for algorithm development and examples from other fields, and evidence and guidelines for intrapartum care. Searches for different algorithm topics were last updated between January and October 2020 and included a combination of terms such as 'labour', 'intrapartum', 'algorithms' and specific topic terms, using Cochrane Library and MEDLINE/PubMED, CINAHL, National Guidelines Clearinghouse and Google. Case scenarios Nine algorithm topics were identified for monitoring and management of uncomplicated labour and childbirth, identification and management of abnormalities of fetal heart rate, liquor, uterine contractions, labour progress, maternal pulse and blood pressure, temperature, urine and complicated third stage of labour. Each topic included between two and four case scenarios covering most common deviations, severity of related complications or critical clinical outcomes. Conclusions Intrapartum care algorithms provide a framework for monitoring women, and identifying and managing complications during labour and childbirth. These algorithms will support implementation of WHO recommendations and facilitate the development by stakeholders of evidence-based, up to date, paper-based or digital reminders and decision-support tools. The algorithms need to be field tested and may need to be adapted to specific contexts. Tweetable abstract Evidence-based intrapartum care clinical algorithms for a safe and positive childbirth experience.

ObjectiveTo examine whether the observed non-inferiority of heat-stable carbetocin (HSC), compared with oxytocin, was influenced by biologic (macrosomia, parity 3 or more, or history of postpartum hemorrhage [PPH]) and/or pharmacologic (induction or augmentation) risk factors for PPH. MethodsThe present study is a secondary analysis of the CHAMPION non-inferiority randomized trial-a two-arm, double-blind, active-controlled study conducted at 23 hospitals in 10 countries, between July 2015 and January 2018. Women with singleton pregnancies, expected to deliver vaginally with cervical dilatation up to 6 cm were eligible. Randomization was stratified by country, with 1:1 assignment. Women in the intervention and control groups received a single intramuscular injection of 100 & mu;g of HSC or 10 IU of oxytocin, respectively. The drugs were administered immediately after birth, and the third stage of labor was managed according to the WHO guidelines. Blood was collected using a plastic drape. For this analysis, we defined a woman as being at risk if she had any one or more of the biologic or pharmacologic risk factor(s). ResultsThe HSC and oxytocin arms contained 14 770 and 14 768 women, respectively. The risk ratios (RR) for PPH were 1.29 (95% confidence interval [CI] 1.08-1.53) or 1.73 (95% CI 1.51-1.98) for those with only biologic (macrosomia, parity 3 or more, and PPH in the previous pregnancy) or only pharmacologic (induced or augmented) risk factors, respectively, compared with those with neither risk factors. ConclusionsFindings reinforce previous evidence that macrosomia, high parity, history of PPH, and induction/augmentation are risk factors for PPH. We did not find a difference in effects between HSC and oxytocin for PPH among women who were neither induced nor augmented or among those who were induced or augmented.

BACKGROUND:Obesity is a major health problem worldwide as it can lead to high blood pressure, heart disease, stroke, diabetes, and insulin resistance. The prevalence of overweight and obesity is increasing worldwide across different age groups. There is evidence of an inverse relationship between calcium intake and body weight. The clinical relevance of a small reduction in body weight has been questioned. However, at a population level, a small effect could mitigate the observed global trends. OBJECTIVES:To assess the effects of calcium supplementation on weight loss in individuals living with overweight or obesity. SEARCH METHODS:We searched CENTRAL, MEDLINE, Embase, LILACS (Latin American and Caribbean Health Science Information database), and two clinical trials registries. The date of the last search of all databases (except Embase) was 10 May 2023. No language restrictions were applied. SELECTION CRITERIA:We included randomised controlled trials evaluating the effect of calcium in participants with overweight or obesity of any age or gender. We excluded studies in participants with absorption problems. We included studies of any dose with a minimum duration of two months. We included the following comparisons: calcium supplementation versus placebo, calcium-fortified food or beverage versus placebo, or calcium-fortified food or beverage versus non-calcium-fortified food or beverage. We excluded studies that evaluated the effect of calcium and vitamin D or mixed minerals compared to placebo. DATA COLLECTION AND ANALYSIS:We used standard methodological procedures expected by Cochrane. Our primary outcomes were body weight, health-related quality of life, and adverse events. Our secondary outcomes were anthropometric measures other than body weight, all-cause mortality, and morbidity. MAIN RESULTS:We found 18 studies that evaluated the effect of calcium compared to placebo or control, with a total of 1873 randomised participants (950 participants in the calcium supplementation groups and 923 in the control groups). All included studies gave oral calcium supplementation as the intervention. We did not find any studies evaluating calcium-fortified foods. We excluded 38 studies, identified four ongoing studies, and listed one study as 'awaiting classification'. Sixteen studies compared calcium supplementation to placebo; two studies compared different doses of calcium supplementation. Doses ranged from very low (0.162 g of calcium/day) to high (1.5 g of calcium/day). Most studies were performed in the USA and Iran, lasted less than six months, and included only women. Low-certainty evidence suggests that calcium supplementation compared to placebo or control may result in little to no difference in body weight (mean difference (MD) -0.15 kg, 95% confidence interval (CI) -0.55 to 0.24; P = 0.45, I2 = 46%; 17 studies, 1317 participants; low-certainty evidence). We downgraded the certainty of the evidence by two levels for risk of bias and heterogeneity. None of the included studies reported health-related quality of life, all-cause mortality, or morbidity/complications as outcomes. Only five studies assessed or reported adverse events. Low-certainty evidence suggests a low frequency of adverse events, with no clear difference between intervention and control groups. Moderate-certainty evidence shows that calcium supplementation compared to placebo or control probably results in a small reduction in body mass index (BMI) (MD -0.18 kg/m2,95% CI -0.22 to -0.13; P < 0.001, I2 = 0%; 9 studies, 731 participants) and waist circumference (MD -0.51 cm, 95% CI -0.72 to -0.29; P < 0.001, I2 = 0%; 6 studies, 273 participants). Low-certainty evidence suggests that calcium supplementation compared to placebo or control may result in a small reduction in body fat mass (MD -0.34 kg, 95% CI -0.73 to 0.05; P < 0.001, I2 = 97%; 12 studies, 812 participants). AUTHORS' CONCLUSIONS:Calcium supplementation for eight weeks to 24 months may result in little to no difference in body weight in people with overweight or obesity. The current evidence is of low certainty, due to concerns regarding risk of bias and statistical heterogeneity. We found that the degree of heterogeneity might be partly explained by calcium dosage, the presence or absence of a co-intervention, and whether an intention-to-treat analysis was pursued. While our analyses suggest that calcium supplementation may result in a small reduction in BMI, waist circumference, and fat mass, this evidence is of low to moderate certainty. Future studies could investigate the effect of calcium supplementation on lean body mass to explore if there is a change in body composition.