Strategies for optimising early detection and obstetric first response management of postpartum haemorrhage at caesarean birth: a modified Delphi-based international expert consensus.

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.

Burden and outcomes of postpartum haemorrhage in Nigerian referral-level hospitals.

OBJECTIVE: To determine the prevalence of primary postpartum haemorrhage (PPH), risk factors, and maternal and neonatal outcomes in a multicentre study across Nigeria. DESIGN: A secondary data analysis using a cross-sectional design. SETTING: Referral-level hospitals (48 public and six private facilities). POPULATION: Women admitted for birth between 1 September 2019 and 31 August 2020. METHODS: Data collected over a 1-year period from the Maternal and Perinatal Database for Quality, Equity and Dignity programme in Nigeria were analysed, stratified by mode of delivery (vaginal or caesarean), using a mixed-effects logistic regression model. MAIN OUTCOME MEASURES: Prevalence of PPH and maternal and neonatal outcomes. RESULTS: Of 68 754 women, 2169 (3.2%, 95% CI 3.07%-3.30%) had PPH, with a prevalence of 2.7% (95% CI 2.55%-2.85%) and 4.0% (95% CI 3.75%-4.25%) for vaginal and caesarean deliveries, respectively. Factors associated with PPH following vaginal delivery were: no formal education (aOR 2.2, 95% CI 1.8-2.6, P < 0.001); multiple pregnancy (aOR 2.7, 95% CI 2.1-3.5, P < 0.001); and antepartum haemorrhage (aOR 11.7, 95% CI 9.4-14.7, P < 0.001). Factors associated with PPH in a caesarean delivery were: maternal age of >35 years (aOR 1.7, 95% CI 1.5-2.0, P < 0.001); referral from informal setting (aOR 2.4, 95% CI 1.4-4.0, P = 0.002); and antepartum haemorrhage (aOR 3.7, 95% CI 2.8-4.7, P < 0.001). Maternal mortality occurred in 4.8% (104/2169) of deliveries overall, and in 8.5% (101/1182) of intensive care unit admissions. One-quarter of all infants were stillborn (570/2307), representing 23.9% (429/1796) of neonatal intensive care unit admissions. CONCLUSIONS: A PPH prevalence of 3.2% can be reduced with improved access to skilled birth attendants.

Outcomes and quality of care for women and their babies after caesarean section in Nigeria.

OBJECTIVE: To describe the outcomes and quality of care for women and their babies after caesarean section (CS) in Nigerian referral-level hospitals. DESIGN: Secondary analysis of a nationwide cross-sectional study. SETTING: Fifty-four referral-level hospitals. POPULATION: All women giving birth in the participating facilities between 1 September 2019 and 31 August 2020. METHODS: Data for the women were extracted, including sociodemographic data, clinical information, mode of birth, and maternal and perinatal outcomes. A conceptual hierarchical framework was employed to explore the sociodemographic and clinical factors associated with maternal and perinatal death in women who had an emergency CS. MAIN OUTCOME MEASURES: Overall CS rate, outcomes for women who had CS, and factors associated with maternal and perinatal mortality. RESULTS: The overall CS rate was 33.3% (22 838/68 640). The majority of CS deliveries were emergency cases (62.8%) and 8.1% of CS deliveries had complications after delivery, which were more common after an emergency CS. There were 179 (0.8%) maternal deaths in women who had a CS and 29.6% resulted from complications of hypertensive disorders of pregnancy. The overall maternal mortality rate in women who delivered by CS was 778 per 100 000 live births, whereas the perinatal mortality at birth was 51 per 1000 live births. Factors associated with maternal mortality in women who had an emergency CS were being <20 or >35 years of age, having a lower level of education and being referred from another facility or informal setting. CONCLUSIONS: One-third of births were delivered via CS (mostly emergency), with almost one in ten women experiencing a complication after a CS. To improve outcomes, hospitals should invest in care and remove obstacles to accessible quality CS services.

Effectiveness and safety of COVID-19 vaccines on maternal and perinatal outcomes: a systematic review and meta-analysis.

OBJECTIVE: To assess the effects of COVID-19 vaccines in women before or during pregnancy on SARS-CoV-2 infection-related, pregnancy, offspring and reactogenicity outcomes. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Major databases between December 2019 and January 2023. STUDY SELECTION: Nine pairs of reviewers contributed to study selection. We included test-negative designs, comparative cohorts and randomised trials on effects of COVID-19 vaccines on infection-related and pregnancy outcomes. Non-comparative cohort studies reporting reactogenicity outcomes were also included. QUALITY ASSESSMENT, DATA EXTRACTION AND ANALYSIS: Two reviewers independently assessed study quality and extracted data. We undertook random-effects meta-analysis and reported findings as HRs, risk ratios (RRs), ORs or rates with 95% CIs. RESULTS: Sixty-seven studies (1 813 947 women) were included. Overall, in test-negative design studies, pregnant women fully vaccinated with any COVID-19 vaccine had 61% reduced odds of SARS-CoV-2 infection during pregnancy (OR 0.39, 95% CI 0.21 to 0.75; 4 studies, 23 927 women; I2=87.2%) and 94% reduced odds of hospital admission (OR 0.06, 95% CI 0.01 to 0.71; 2 studies, 868 women; I2=92%). In adjusted cohort studies, the risk of hypertensive disorders in pregnancy was reduced by 12% (RR 0.88, 95% CI 0.82 to 0.92; 2 studies; 115 085 women), while caesarean section was reduced by 9% (OR 0.91, 95% CI 0.85 to 0.98; 6 studies; 30 192 women). We observed an 8% reduction in the risk of neonatal intensive care unit admission (RR 0.92, 95% CI 0.87 to 0.97; 2 studies; 54 569 women) in babies born to vaccinated versus not vaccinated women. In general, vaccination during pregnancy was not associated with increased risk of adverse pregnancy or perinatal outcomes. Pain at the injection site was the most common side effect reported (77%, 95% CI 52% to 94%; 11 studies; 27 195 women). CONCLUSION: COVID-19 vaccines are effective in preventing SARS-CoV-2 infection and related complications in pregnant women. PROSPERO REGISTRATION NUMBER: CRD42020178076.

Maternal and perinatal health research during emerging and ongoing epidemic threats: a landscape analysis and expert consultation.

INTRODUCTION: Pregnant women and their offspring are often at increased direct and indirect risks of adverse outcomes during epidemics and pandemics. A coordinated research response is paramount to ensure that this group is offered at least the same level of disease prevention, diagnosis, and care as the general population. We conducted a landscape analysis and held expert consultations to identify research efforts relevant to pregnant women affected by disease outbreaks, highlight gaps and challenges, and propose solutions to addressing them in a coordinated manner. METHODS: Literature searches were conducted from 1 January 2015 to 22 March 2022 using Web of Science, Google Scholar and PubMed augmented by key informant interviews. Findings were reviewed and Quid analysis was performed to identify clusters and connectors across research networks followed by two expert consultations. These formed the basis for the development of an operational framework for maternal and perinatal research during epidemics. RESULTS: Ninety-four relevant research efforts were identified. Although well suited to generating epidemiological data, the entire infrastructure to support a robust research response remains insufficient, particularly for use of medical products in pregnancy. Limitations in global governance, coordination, funding and data-gathering systems have slowed down research responses. CONCLUSION: Leveraging current research efforts while engaging multinational and regional networks may be the most effective way to scale up maternal and perinatal research preparedness and response. The findings of this landscape analysis and proposed operational framework will pave the way for developing a roadmap to guide coordination efforts, facilitate collaboration and ultimately promote rapid access to countermeasures and clinical care for pregnant women and their offspring in future epidemics.

Vulnerabilities and reparative strategies during pregnancy, childbirth, and the postpartum period: moving from rhetoric to action.

Maternal outcomes throughout pregnancy, childbirth, and the postnatal period are influenced by interlinked and interdependent vulnerabilities. A comprehensive understanding of how various threats and barriers affect maternal and perinatal health is critical to plan, evaluate and improve maternal health programmes. This paper builds on the introductory paper of the Series on the determinants of maternal health by assessing vulnerabilities during pregnancy, childbirth, and the postnatal period. We synthesise and present the concept of vulnerability in pregnancy and childbirth, and map vulnerability attributes and their dynamic influence on maternal outcomes in early and late pregnancy and during childbirth and the postnatal period, with a particular focus on low-income and middle-income countries (LMICs). We summarise existing literature and present the evidence on the effects of various reparative strategies to improve pregnancy and childbirth outcomes. Lastly, we discuss the implications of the identified vulnerability attributes and reparative strategies for the efforts of policymakers, healthcare professionals, and researchers working towards improving outcomes for women and birthing people in LMICs.

Towards a better tomorrow: addressing intersectional gender power relations to eradicate inequities in maternal health.

An equity lens to maternal health has typically focused on assessing the differences in coverage and use of healthcare services and critical interventions. While this approach is important, we argue that healthcare experiences, dignity, rights, justice, and well-being are fundamental components of high quality and person-centred maternal healthcare that must also be considered. Looking at differences across one dimension alone does not reflect how fundamental drivers of maternal health inequities-including racism, ethnic or caste-based discrimination, and gendered power relations-operate. In this paper, we describe how using an intersectionality approach to maternal health can illuminate how power and privilege (and conversely oppression and exclusion) intersect and drive inequities. We present an intersectionality-informed analysis on antenatal care quality to illustrate the advantages of this approach, and what is lost in its absence. We reviewed and mapped equity-informed interventions in maternal health to existing literature to identify opportunities for improvement and areas for innovation. The gaps and opportunities identified were then synthesised to propose recommendations on how to apply an intersectionality lens to maternal health research, programmes, and policies.

Unveiling the strong positive relationship: Maternal characteristics and neonatal outcomes in the Better Outcomes in Labour Difficulty (BOLD) study - a secondary analysis validating neonatal near miss classification.

Background: The near miss concept, denoting near collisions between aircraft, originated in aeronautics, but has recently been transferred to the neonatal context as a way of evaluating the quality of health services for newborns, especially in settings with reduced child mortality. However, there is yet no consensus regarding the underlying criteria. The most common indicators used to assess health care quality include mortality (maternal and neonatal) and life-threatening conditions. Using the World Health Organization (WHO) Better Outcomes in Labour Difficulty (BOLD) prospective cohort study data set, we conducted a secondary analysis to validate the near miss concept and explore the association between maternal and neonatal outcomes. Methods: We studied 10 203 singleton mothers treated between December 2014 and November 2015 in nine Nigerian and four Ugandan hospitals. We validated the near miss concept by testing the diagnostic accuracy (sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and odds ratio (OR)) using death as the reference variable and calculating the maternal and neonatal case fatality rates. We performed ordinal and binomial logistic regression, with the independent variables being those that had P < 0.1 in the univariate analyses. We considered the significance level of 5%. Results: We validated the neonatal near miss concept using the BOLD study data. We observed maternal and neonatal case fatality rates of 70.2% and 6.5%, with an increasing severity relationship between maternal and neonatal outcomes (P < 0.05). Ordinal logistic regression showed that gestational age <37 or >41 weeks and <8 antenatal consultations were related to a higher risk of neonatal severe outcomes, while maternal age between 30 and 34 years functioned as a protective factor against severe neonatal outcomes (SNO). Binomial logistic regression showed gestational age <37(OR = 1.46; 95% confidence interval (CI) = 1.07-1.94) or >41 weeks (OR = 2.26; 95% CI = 1.55-3.20), low educational level (OR = 1.76; 95% CI = 1.12-2.69), overweight/obesity (OR = 1.23; 95% CI = 1.02-1.47), one previous cesarean section (OR = 1.90; 95% CI = 1.36-2.61), one previous abortion (OR = 1.25; 95% CI = 1.00-1.56), and previous chronic condition (OR = 1.83; 95% CI = 1.37-2.41) were risk factors for SNO. Conclusions: The neonatal near miss concept could be used as a parameter for analysis in different health systems, to ensure that measuring of neonatal severity is comparable across health care units. In this analysis, we observed a progressive association between maternal severity and the severity of the newborns' outcomes.

Neglected medium-term and long-term consequences of labour and childbirth: a systematic analysis of the burden, recommended practices, and a way forward.

Over the past three decades, substantial progress has been made in reducing maternal mortality worldwide. However, the historical focus on mortality reduction has been accompanied by comparative neglect of labour and birth complications that can emerge or persist months or years postnatally. This paper addresses these overlooked conditions, arguing that their absence from the global health agenda and national action plans has led to the misconception that they are uncommon or unimportant. The historical limitation of postnatal care services to the 6 weeks after birth is also a contributing factor. We reviewed epidemiological data on medium-term and long-term complications arising from labour and childbirth beyond 6 weeks, along with high-quality clinical guidelines for their prevention, identification, and treatment. We explore the complex interplay of human evolution, maternal physiology, and inherent predispositions that contribute to these complications. We offer actionable recommendations to change the current trajectories of these neglected conditions and help achieve the targets of Sustainable Development Goal 3. This paper is the third in a Series of four papers about maternal health in the perinatal period and beyond.

A global analysis of the determinants of maternal health and transitions in maternal mortality.

The reduction of maternal mortality and the promotion of maternal health and wellbeing are complex tasks. This Series paper analyses the distal and proximal determinants of maternal health, as well as the exposures, risk factors, and micro-correlates related to maternal mortality. This paper also examines the relationship between these determinants and the gradual shift over time from a pattern of high maternal mortality to a pattern of low maternal mortality (a phenomenon described as the maternal mortality transition). We conducted two systematic reviews of the literature and we analysed publicly available data on indicators related to the Sustainable Development Goals, specifically, estimates prepared by international organisations, including the UN and the World Bank. We considered 23 frameworks depicting maternal health and wellbeing as a multifactorial process, with superdeterminants that broadly affect women's health and wellbeing before, during, and after pregnancy. We explore the role of social determinants of maternal health, individual characteristics, and health-system features in the production of maternal health and wellbeing. This paper argues that the preventable deaths of millions of women each decade are not solely due to biomedical complications of pregnancy, childbirth, and the postnatal period, but are also tangible manifestations of the prevailing determinants of maternal health and persistent inequities in global health and socioeconomic development. This paper underscores the need for broader, multipronged actions to improve maternal health and wellbeing and accelerate sustainable reductions in maternal mortality. For women who have pregnancy, childbirth, or postpartum complications, the health system provides a crucial opportunity to interrupt the chain of events that can potentially end in maternal death. Ultimately, expanding the health sector ecosystem to mitigate maternal health determinants and tailoring the configuration of health systems to counter the detrimental effects of eco-social forces, including though increased access to quality-assured commodities and services, are essential to improve maternal health and wellbeing and reduce maternal mortality.

The use of network meta-analysis in updating WHO living maternal and perinatal health recommendations.

Drawing on two recent examples of WHO living guidelines in maternal and perinatal health, this paper elucidates a pragmatic, stepwise approach to using network meta-analysis (NMA) in guideline development in the presence of multiple treatment options. NMA has important advantages. These include the ability to compare multiple interventions in a single coherent analysis, provide direct estimates of the relative effects of all available interventions, infer indirect effect estimates for interventions not directly compared and generate rankings of the available treatment options. It can be difficult to harness these advantages in the face of a lack of current guidance on using NMA evidence in guideline development, with several challenges emerging. Challenges include the choice of conceptual approach, the volume and complexity of the evidence, the contribution of treatment rankings, and the fact that the preferable treatment is not always obvious. This paper describes a layered approach to resolving these challenges, which supports systematic guideline decision-making and development of trustworthy clinical guidelines when multiple treatment options are available.

Perceptions and experiences of the prevention, detection, and management of postpartum haemorrhage: a qualitative evidence synthesis.

BACKGROUND: Postpartum haemorrhage (PPH), defined as blood loss of 500 mL or more after childbirth, is the leading cause of maternal mortality worldwide. It is possible to prevent complications of PPH with timely and appropriate detection and management. However, implementing the best methods of PPH prevention, detection and management can be challenging, particularly in low- and middle-income countries. OBJECTIVES: Our overall objective was to explore the perceptions and experiences of women, community members, lay health workers, and skilled healthcare providers who have experience with PPH or with preventing, detecting, and managing PPH, in community or health facility settings. SEARCH METHODS: We searched MEDLINE, CINAHL, Scopus, and grey literature on 13 November 2022 with no language restrictions. We then performed reference checking and forward citation searching of the included studies. SELECTION CRITERIA: We included qualitative studies and mixed-methods studies with an identifiable qualitative component. We included studies that explored perceptions and experiences of PPH prevention, detection, and management among women, community members, traditional birth attendants, healthcare providers, and managers. DATA COLLECTION AND ANALYSIS: We used three-stage maximum variation sampling to ensure diversity in terms of relevance of the study to the review objectives, richness of data, and coverage of critical contextual elements: setting (region, country income level), perspective (type of participant), and topic (prevention, detection, management). We extracted data using a data extraction form designed for this review. We used thematic synthesis to analyse and synthesise the evidence, and we used the GRADE-CERQual (Confidence in the Evidence from Reviews of Qualitative research) approach to assess our confidence in each finding. To identify factors that may influence intervention implementation, we mapped each review finding to the Theoretical Domains Framework (TDF) and the Capability, Motivation, and Opportunity model of Behaviour change (COM-B). We used the Behaviour Change Wheel to explore implications for practice. MAIN RESULTS: We included 67 studies and sampled 43 studies for our analysis. Most were from low- or middle-income countries (33 studies), and most included the perspectives of women and health workers. We downgraded our confidence in several findings from high confidence to moderate, low, or very-low confidence, mainly due to concerns about how the studies were conducted (methodological limitations) or concerns about missing important perspectives from some types of participants or in some settings (relevance). In many communities, bleeding during and after childbirth is considered "normal" and necessary to expel "impurities" and restore and cleanse the woman's body after pregnancy and birth (moderate confidence). In some communities, people have misconceptions about causes of PPH or believe that PPH is caused by supernatural powers or evil spirits that punish women for ignoring or disobeying social rules or for past mistakes (high confidence). For women who give birth at home or in the community, female family members or traditional birth attendants are the first to recognise excess bleeding after birth (high confidence). Family members typically take the decision of whether and when to seek care if PPH is suspected, and these family members are often influenced by trusted traditional birth attendants or community midwives (high confidence). If PPH is identified for women birthing at home or in the community, decision-making about the subsequent referral and care pathway can be multifaceted and complex (high confidence). First responders to PPH are not always skilled or trained healthcare providers (high confidence). In health facilities, midwives may consider it easy to implement visual estimation of blood loss with a kidney dish or under-pad, but difficult to accurately interpret the amount of blood loss (very low confidence). Quantifying (rather than estimating) blood loss may be a complex and contentious change of practice for health workers (low confidence). Women who gave birth in health facilities and experienced PPH described it as painful, embarrassing, and traumatic. Partners or other family members also found the experience stressful. While some women were dissatisfied with their level of involvement in decision-making for PPH management, others felt health workers were best placed to make decisions (moderate confidence). Inconsistent availability of resources (drugs, medical supplies, blood) causes delays in the timely management of PPH (high confidence). There is limited availability of misoprostol in the community owing to stockouts, poor supply systems, and the difficulty of navigating misoprostol procurement for community health workers (moderate confidence). Health workers described working on the maternity ward as stressful and intense due to short staffing, long shifts, and the unpredictability of emergencies. Exhausted and overwhelmed staff may be unable to appropriately monitor all women, particularly when multiple women are giving birth simultaneously or on the floor of the health facility; this could lead to delays in detecting PPH (moderate confidence). Inadequate staffing, high turnover of skilled health workers, and appointment of lower-level cadres of health workers are key challenges to the provision of quality PPH care (high confidence). Through team-based simulation training, health workers of different cadres (doctors, midwives, lay health workers) can develop a shared mental model to help them work quickly, efficiently, and amicably as a team when managing women with PPH (moderate confidence). AUTHORS' CONCLUSIONS: Our findings highlight how improving PPH prevention, detection, and management is underpinned by a complex system of interacting roles and behaviours (community, women, health workers of different types and with different experiences). Multiple individual, sociocultural, and environmental factors influence the decisions and behaviours of women, families, communities, health workers, and managers. It is crucial to consider the broader health and social systems when designing and implementing PPH interventions to change or influence these behaviours. We have developed a set of prompts that may help programme managers, policymakers, researchers, and other key stakeholders to identify and address factors that affect implementation and scale-up of interventions to improve PPH prevention, detection, and management.

Alternative magnesium sulphate regimens for women with pre-eclampsia and eclampsia.

BACKGROUND: Magnesium sulphate is the drug of choice for the prevention and treatment of women with eclampsia. Regimens for administration of this drug have evolved over the years, but there is no clarity on the comparative benefits or harm of alternative regimens. This is an update of a review first published in 2010. OBJECTIVES: To assess if one magnesium sulphate regimen is better than another when used for the care of women with pre-eclampsia or eclampsia, or both, to reduce the risk of severe morbidity and mortality for the woman and her baby. SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (29 April 2022), and reference lists of retrieved studies. SELECTION CRITERIA: We included randomised trials and cluster-randomised trials comparing different regimens for administration of magnesium sulphate used in women with pre-eclampsia or eclampsia, or both. Comparisons included different dose regimens, intramuscular versus intravenous route for maintenance therapy, and different durations of therapy. We excluded studies with quasi-random or cross-over designs. We included abstracts of conference proceedings if compliant with the trustworthiness assessment. DATA COLLECTION AND ANALYSIS: For this update, two review authors assessed trials for inclusion, performed risk of bias assessment, and extracted data. We checked data for accuracy. We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: For this update, a total of 16 trials (3020 women) met our inclusion criteria: four trials (409 women) compared regimens for women with eclampsia, and 12 trials (2611 women) compared regimens for women with pre-eclampsia. Most of the included trials had small sample sizes and were conducted in low- and middle-income countries. Eleven trials reported adequate randomisation and allocation concealment. Blinding of participants and clinicians was not possible in most trials. The included studies were for the most part at low risk of attrition and reporting bias. Treatment of women with eclampsia (four comparisons) One trial compared a loading dose-alone regimen with a loading dose plus maintenance dose regimen (80 women). It is uncertain whether either regimen has an effect on the risk of recurrence of convulsions or maternal death (very low-certainty evidence). One trial compared a lower-dose regimen with standard-dose regimen over 24 hours (72 women). It is uncertain whether either regimen has an effect on the risk of recurrence of convulsion, severe morbidity, perinatal death, or maternal death (very low-certainty evidence). One trial (137 women) compared intravenous (IV) versus standard intramuscular (IM) maintenance regimen. It is uncertain whether either route has an effect on recurrence of convulsions, death of the baby before discharge (stillbirth and neonatal death), or maternal death (very low-certainty evidence). One trial (120 women) compared a short maintenance regimen with a standard (24 hours after birth) maintenance regimen. It is uncertain whether the duration of the maintenance regimen has an effect on recurrence of convulsions, severe morbidity, or side effects such as nausea and respiratory failure. A short maintenance regimen may reduce the risk of flushing when compared to a standard 24 hours maintenance regimen (risk ratio (RR) 0.27, 95% confidence interval (CI) 0.08 to 0.93; 1 trial, 120 women; low-certainty evidence). Many of our prespecified critical outcomes were not reported in the included trials. Prevention of eclampsia for women with pre-eclampsia (five comparisons) Two trials (462 women) compared loading dose alone with loading dose plus maintenance therapy. Low-certainty evidence suggests an uncertain effect with either regimen on the risk of eclampsia (RR 2.00, 95% CI 0.61 to 6.54; 2 trials, 462 women) or perinatal death (RR 0.50, 95% CI 0.19 to 1.36; 2 trials, 462 women). One small trial (17 women) compared an IV versus IM maintenance regimen for 24 hours. It is uncertain whether IV or IM maintenance regimen has an effect on eclampsia or stillbirth (very low-certainty evidence). Four trials (1713 women) compared short postpartum maintenance regimens with continuing for 24 hours after birth. Low-certainty evidence suggests there may be a wide range of benefit or harm between groups regarding eclampsia (RR 1.99, 95% CI 0.18 to 21.87; 4 trials, 1713 women). Low-certainty evidence suggests there may be little or no effect on severe morbidity (RR 0.96, 95% CI 0.71 to 1.29; 2 trials, 1233 women) or side effects such as respiratory depression (RR 0.80, 95% CI 0.25 to 2.61; 2 trials, 1424 women). Three trials (185 women) compared a higher-dose maintenance regimen versus a lower-dose maintenance regimen. It is uncertain whether either regimen has an effect on eclampsia (very low-certainty evidence). Low-certainty evidence suggests that a higher-dose maintenance regimen has little or no effect on side effects when compared to a lower-dose regimen (RR 0.79, 95% CI 0.61 to 1.01; 1 trial 62 women). One trial (200 women) compared a maintenance regimen by continuous infusion versus a serial IV bolus regimen. It is uncertain whether the duration of the maintenance regimen has an effect on eclampsia, side effects, perinatal death, maternal death, or other neonatal morbidity (very low-certainty evidence). Many of our prespecified critical outcomes were not reported in the included trials. AUTHORS' CONCLUSIONS: Despite the number of trials evaluating various magnesium sulphate regimens for eclampsia prophylaxis and treatment, there is still no compelling evidence that one particular regimen is more effective than another. Well-designed randomised controlled trials are needed to answer this question.

Randomized Trial of Early Detection and Treatment of Postpartum Hemorrhage.

BACKGROUND: Delays in the detection or treatment of postpartum hemorrhage can result in complications or death. A blood-collection drape can help provide objective, accurate, and early diagnosis of postpartum hemorrhage, and delayed or inconsistent use of effective interventions may be able to be addressed by a treatment bundle. METHODS: We conducted an international, cluster-randomized trial to assess a multicomponent clinical intervention for postpartum hemorrhage in patients having vaginal delivery. The intervention included a calibrated blood-collection drape for early detection of postpartum hemorrhage and a bundle of first-response treatments (uterine massage, oxytocic drugs, tranexamic acid, intravenous fluids, examination, and escalation), supported by an implementation strategy (intervention group). Hospitals in the control group provided usual care. The primary outcome was a composite of severe postpartum hemorrhage (blood loss, ≥1000 ml), laparotomy for bleeding, or maternal death from bleeding. Key secondary implementation outcomes were the detection of postpartum hemorrhage and adherence to the treatment bundle. RESULTS: A total of 80 secondary-level hospitals across Kenya, Nigeria, South Africa, and Tanzania, in which 210,132 patients underwent vaginal delivery, were randomly assigned to the intervention group or the usual-care group. Among hospitals and patients with data, a primary-outcome event occurred in 1.6% of the patients in the intervention group, as compared with 4.3% of those in the usual-care group (risk ratio, 0.40; 95% confidence interval [CI], 0.32 to 0.50; P<0.001). Postpartum hemorrhage was detected in 93.1% of the patients in the intervention group and in 51.1% of those in the usual-care group (rate ratio, 1.58; 95% CI, 1.41 to 1.76), and the treatment bundle was used in 91.2% and 19.4%, respectively (rate ratio, 4.94; 95% CI, 3.88 to 6.28). CONCLUSIONS: Early detection of postpartum hemorrhage and use of bundled treatment led to a lower risk of the primary outcome, a composite of severe postpartum hemorrhage, laparotomy for bleeding, or death from bleeding, than usual care among patients having vaginal delivery. (Funded by the Bill and Melinda Gates Foundation; E-MOTIVE ClinicalTrials.gov number, NCT04341662.).

New insights on labor progression: a systematic review.

The past 20 years witnessed an invigoration of research on labor progression and a change of thinking regarding normal labor. New evidence is emerging, and more advanced statistical methods are applied to labor progression analyses. Given the wide variations in the onset of active labor and the pattern of labor progression, there is an emerging consensus that the definition of abnormal labor may not be related to an idealized or average labor curve. Alternative approaches to guide labor management have been proposed; for example, using an upper limit of a distribution of labor duration to define abnormally slow labor. Nonetheless, the methods of labor assessment are still primitive and subject to error; more objective measures and more advanced instruments are needed to identify the onset of active labor, monitor labor progression, and define when labor duration is associated with maternal/child risk. Cervical dilation alone may be insufficient to define active labor, and incorporating more physical and biochemical measures may improve accuracy of diagnosing active labor onset and progression. Because the association between duration of labor and perinatal outcomes is rather complex and influenced by various underlying and iatrogenic conditions, future research must carefully explore how to integrate statistical cut-points with clinical outcomes to reach a practical definition of labor abnormalities. Finally, research regarding the complex labor process may benefit from new approaches, such as machine learning technologies and artificial intelligence to improve the predictability of successful vaginal delivery with normal perinatal outcomes.

Effect of antenatal corticosteroid administration-to-birth interval on maternal and newborn outcomes: a systematic review.

Background: Antenatal corticosteroids (ACS) are highly effective at improving outcomes for preterm newborns. Evidence suggests the benefits of ACS may vary with the time interval between administration-to-birth. However, the optimal ACS administration-to-birth interval is not yet known. In this systematic review, we synthesised available evidence on the relationship between ACS administration-to-birth interval and maternal and newborn outcomes. Methods: This review was registered with PROSPERO (CRD42021253379). We searched Medline, Embase, CINAHL, Cochrane Library, Global Index Medicus on 11 Nov 2022 with no date or language restrictions. Randomised and non-randomised studies of pregnant women receiving ACS for preterm birth where maternal and newborn outcomes were reported for different administration-to-birth intervals were eligible. Eligibility screening, data extraction and risk of bias assessment were performed by two authors independently. Fetal and neonatal outcomes included perinatal and neonatal mortality, preterm birth-related morbidity outcomes and mean birthweight. Maternal outcomes included chorioamnionitis, maternal mortality, endometritis, and maternal intensive care unit admission. Findings: Ten trials (4592 women; 5018 neonates), 45 cohort studies (at least 22,992 women; 30,974 neonates) and two case-control studies (355 women; 360 neonates) met the eligibility criteria. Across studies, 37 different time interval combinations were identified. There was considerable heterogeneity in included administration-to-birth intervals and populations. The odds of neonatal mortality, respiratory distress syndrome and intraventricular haemorrhage were associated with the ACS administration-to-birth interval. However, the interval associated with the greatest improvements in newborn outcomes was not consistent across studies. No reliable data were available for maternal outcomes, though odds of chorioamnionitis might be associated with longer intervals. Intepretation: An optimal ACS administration-to-birth interval likely exists, however variations in study design limit identification of this interval from available evidence. Future research should consider advanced analysis techniques such as individual patient data meta-analysis to identify which ACS administration-to-birth intervals are most beneficial, and how these benefits can be optimised for women and newborns. Funding: This study was conducted with funding support from the UNDP-UNFPA-UNICEF-WHO-World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), Department of Sexual and Reproductive Health and Research (SRH), a co-sponsored programme executed by the World Health Organization.

A core outcome set for trials in miscarriage management and prevention: An international consensus development study.

OBJECTIVE: To develop core outcome sets (COS) for miscarriage management and prevention. DESIGN: Modified Delphi survey combined with a consensus development meeting. SETTING: International. POPULATION: Stakeholder groups included healthcare providers, international experts, researchers, charities and couples with lived experience of miscarriage from 15 countries: 129 stakeholders for miscarriage management and 437 for miscarriage prevention. METHODS: Modified Delphi method and modified nominal group technique. RESULTS: The final COS for miscarriage management comprises six outcomes: efficacy of treatment, heavy vaginal bleeding, pelvic infection, maternal death, treatment or procedure-related complications, and patient satisfaction. The final COS for miscarriage prevention comprises 12 outcomes: pregnancy loss <24 weeks' gestation, live birth, gestation at birth, pre-term birth, congenital abnormalities, fetal growth restriction, maternal (antenatal) complications, compliance with intervention, patient satisfaction, maternal hospitalisation, neonatal or infant hospitalisation, and neonatal or infant death. Other outcomes identified as important were mental health-related outcomes, future fertility and health economic outcomes. CONCLUSIONS: This study has developed two core outcome sets, through robust methodology, that should be implemented across future randomised trials and systematic reviews in miscarriage management and prevention. This work will help to standardise outcome selection, collection and reporting, and improve the quality and safety of future studies in miscarriage.