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Objective: To predict birth weight at various potential gestational ages of delivery based on data routinely available at the first antenatal visit., Design: Individual participant data meta-analysis., Data Sources: Individual participant data of four cohorts (237 228 pregnancies) from the International Prediction of Pregnancy Complications (IPPIC) network dataset., Eligibility Criteria for Selecting Studies: Studies in the IPPIC network were identified by searching major databases for studies reporting risk factors for adverse pregnancy outcomes, such as pre-eclampsia, fetal growth restriction, and stillbirth, from database inception to August 2019. Data of four IPPIC cohorts (237 228 pregnancies) from the US (National Institute of Child Health and Human Development, 2018; 233 483 pregnancies), UK (Allen et al, 2017; 1045 pregnancies), Norway (STORK Groruddalen research programme, 2010; 823 pregnancies), and Australia (Rumbold et al, 2006; 1877 pregnancies) were included in the development of the model., Results: The IPPIC birth weight model was developed with random intercept regression models with backward elimination for variable selection. Internal-external cross validation was performed to assess the study specific and pooled performance of the model, reported as calibration slope, calibration-in-the-large, and observed versus expected average birth weight ratio. Meta-analysis showed that the apparent performance of the model had good calibration (calibration slope 0.99, 95% confidence interval (CI) 0.88 to 1.10; calibration-in-the-large 44.5 g, -18.4 to 107.3) with an observed versus expected average birth weight ratio of 1.02 (95% CI 0.97 to 1.07). The proportion of variation in birth weight explained by the model (R 2 ) was 46.9% (range 32.7-56.1% in each cohort). On internal-external cross validation, the model showed good calibration and predictive performance when validated in three cohorts with a calibration slope of 0.90 (Allen cohort), 1.04 (STORK Groruddalen cohort), and 1.07 (Rumbold cohort), calibration-in-the-large of -22.3 g (Allen cohort), -33.42 (Rumbold cohort), and 86.4 g (STORK Groruddalen cohort), and observed versus expected ratio of 0.99 (Rumbold cohort), 1.00 (Allen cohort), and 1.03 (STORK Groruddalen cohort); respective pooled estimates were 1.00 (95% CI 0.78 to 1.23; calibration slope), 9.7 g (-154.3 to 173.8; calibration-in-the-large), and 1.00 (0.94 to 1.07; observed v expected ratio). The model predictions were more accurate (smaller mean square error) in the lower end of predicted birth weight, which is important in informing clinical decision making., Conclusions: The IPPIC birth weight model allowed birth weight predictions for a range of possible gestational ages. The model explained about 50% of individual variation in birth weights, was well calibrated (especially in babies at high risk of fetal growth restriction and its complications), and showed promising performance in four different populations included in the individual participant data meta-analysis. Further research to examine the generalisability of performance in other countries, settings, and subgroups is required., Trial Registration: PROSPERO CRD42019135045., Competing Interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from the National Institute for Health and Care Research Health Technology Assessment UK programme for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work., (Copyright © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To measure the proportion of women's preferences for CS in hospitals with high caesarean section rates and to identify related factors., Design: A cross-sectional hospital-based postpartum survey was conducted. We used multilevel multivariate logistic regression and probit models to analyse the association between women's caesarean section preferences and maternal characteristics. Probit models take into account selection bias while excluding women who had no preference., Setting: Thirty-two hospitals in Argentina, Thailand, Vietnam and Burkina Faso were selected., Participants: A total of 1,979 post-partum women with no potential medical need for caesarean section were included among a representative sample of women who delivered at each of the participating facilities during the data collection period., Findings: The overall caesarean section rate was 23.3 %. Among women who declared a preference in late pregnancy, 9 % preferred caesarean section, ranging from 1.8 % in Burkina Faso to 17.8 % in Thailand. Primiparous women were more likely to prefer a caesarean section than multiparous women (β=+0.16 [+0.01; +0.31]; p = 0.04). Among women who preferred caesarean section, doctors were frequently cited as the main influencers, and "avoid pain in labour" was the most common perceived benefit of caesarean section., Key Conclusions: Our results suggest that a high proportion of women prefer vaginal birth and highlight that the preference for caesarean section is linked to women's fear of pain and the influence of doctors. These results can inform the development of interventions aimed at supporting women and their preferences, providing them with evidence-based information and changing doctors' behaviour in order to reduce the number of unnecessary caesarean sections., Clinical Trial Registry: The QUALI-DEC trial is registered on the Current Controlled Trials website (https://www.isrctn.com/) under the number ISRCTN67214403., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

The third stage of labor is defined as the time period between delivery of the fetus through delivery of the placenta. During a normal third stage, uterine contractions lead to separation and expulsion of the placenta from the uterus. Postpartum hemorrhage is a relatively common complication of the third stage of labor. Strategies have been studied to mitigate the risk of postpartum hemorrhage, leading to the widespread implementation of active management of the third stage of labor. Initially, active management of the third stage of labor consisted of a bundle of interventions including administration of a uterotonic agent, early cord clamping, controlled cord traction, and external uterine massage. However, the effectiveness of these interventions as a bundle has been questioned, leading to abandonment of some components in recent years. Despite this, upon review of selected international guidelines, we found that the term "active management of the third stage of labor" was still used, but recommendations for and against individual interventions were variable and not necessarily supported by current evidence. In this review, we: (1) examine the physiology of the third stage of labor, (2) present evidence related to interventions that prevent postpartum hemorrhage and promote maternal and neonatal health, (3) review current global guidelines and recommendations for practice, and (4) propose future areas of investigation. The interventions in this review include pharmacologic agents to prevent postpartum hemorrhage, cord clamping, cord milking, cord traction, cord drainage, early skin-to-skin contact, and nipple stimulation. Treatment of complications of the third stage of labor is outside of the scope of this review. We conclude that current evidence supports the use of effective pharmacologic postpartum hemorrhage prophylaxis, delayed cord clamping, early skin-to-skin contact, and controlled cord traction at delivery when feasible. The most effective uterotonic regimens for preventing postpartum hemorrhage after vaginal delivery include oxytocin plus ergometrine; oxytocin plus misoprostol; or carbetocin. After cesarean delivery, carbetocin or oxytocin as a bolus are the most effective regimens. There is inconsistent evidence regarding the use of tranexamic acid in addition to a uterotonic compared with a uterotonic alone for postpartum hemorrhage prevention after all deliveries. Because of differences in patient comorbidities, costs, and availability of resources and staff, decisions to use specific prevention strategies are dependent on patient- and system-level factors. We recommend that the term "active management of the third stage of labor" as a combined intervention no longer be used. Instead, we recommend that "third stage care" be adopted, which promotes the implementation of evidence-based interventions that incorporate practices that are safe and beneficial for both the woman and neonate., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Access to comprehensive abortion care could prevent the death of between 13 865 and 38 940 women and the associated morbidity of 5 million women worldwide. There have been some important improvements in Latin America in terms of laws and policies on abortion. However, the predominant environment is still restrictive, and many women, adolescents and girls still face multiple barriers to exercise their reproductive rights. This research will systematically assess comprehensive abortion policies in five Latin American countries (Argentina, Colombia, Honduras, Mexico and Uruguay). The aim is to identify barriers, facilitators and strategies to the implementation of abortion policies, looking at four key dimensions-regulatory framework, abortion policy dynamics, abortion service delivery and health system and health outcomes indicators-to draw cross-cutting lessons learnt to improve current implementation and inform future safe abortion policy development., Methods and Analysis: A mixed-method design will be used in the five countries to address the four dimensions through the Availability, Accessibility, Acceptability and Quality of Care model. The data collection tools include desk reviews and semi-structured interviews with key actors. Analysis will be performed using thematic analysis and stakeholder analysis. A regional synthesis exercise will be conducted to draw lessons on barriers, facilitators and the strategies., Ethics and Dissemination: The project has been approved by the WHO Research Ethics Review Committee (ID: A66023) and by the local research ethics committees. Informed consent will be obtained from participants. Data will be treated with careful attention to protecting privacy and confidentiality. Findings from the study will be disseminated through a multipurpose strategy to target diverse audiences to foster the use of the study findings to inform the public debate agenda and policy implementation at national level. The strategy will include academic, advocacy and policy arenas and actors, including peer-reviewed publication and national and regional dissemination workshops., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: Improving the understanding of non-clinical factors that lead to the increasing caesarean section (CS) rates in many low- and middle-income countries is currently necessary to meet the challenge of implementing effective interventions in hospitals to reverse the trend. The objective of this study was to study the influence of organizational factors on the CS use in Argentina, Vietnam, Thailand and Burkina Faso., Methods: A cross-sectional hospital-based postpartum survey was conducted in 32 hospitals (8 per country). We selected women with no potential medical need for CS among a random sample of women who delivered at each of the participating facilities during the data collection period. We used multilevel multivariable logistic regression to analyse the association between CS use and organizational factors, adjusted on women's characteristics., Results: A total of 2,092 low-risk women who had given birth in the participating hospitals were included. The overall CS rate was 24.1%, including 4.9% of pre-labour CS and 19.3% of intra-partum CS. Pre-labour CS was significantly associated with a 24-hour anaesthetist dedicated to the delivery ward (ORa = 3.70 [1.41; 9.72]) and with the possibility to have an individual room during labour and delivery (ORa = 0.28 [0.09; 0.87]). Intra-partum CS was significantly associated with a higher bed occupancy level (ORa = 1.45 [1.09; 1.93]): intrapartum CS rate would increase of 6.3% points if the average number of births per delivery bed per day increased by 10%., Conclusion: Our results suggest that organisational norms and convenience associated with inadequate use of favourable resources, as well as the lack of privacy favouring women's preference for CS, and the excessive workload of healthcare providers drive the CS overuse in these hospitals. It is also crucial to enhance human and physical resources in delivery rooms and the organisation of intrapartum care to improve the birth experience and the working environment for those providing care., Trial Registration: The QUALI-DEC trial is registered on the Current Controlled Trials website ( https://www.isrctn.com/ ) under the number ISRCTN67214403., (© 2024. The Author(s).)

The project 'Quality Decision-making by women and providers' (QUALI-DEC) combines four non-clinical interventions to promote informed decision-making surrounding mode of birth, improve women's birth experiences, and reduce caesarean sections among low-risk women. QUALI-DEC is currently being implemented in 32 healthcare facilities across Argentina, Burkina Faso, Thailand, and Viet Nam. In this paper, we detail implementation processes and the planned process evaluation, which aims to assess how and for whom QUALI-DEC worked, the mechanisms of change and their interactions with context and setting; adaptations to intervention and implementation strategies, feasibility of scaling-up, and cost-effectiveness of the intervention. We developed a project theory of change illustrating how QUALI-DEC might lead to impact. The theory of change, together with on the ground observations of implementation processes, guided the process evaluation strategy including what research questions and perspectives to prioritise. Main data sources will include: 1) regular monitoring visits in healthcare facilities, 2) quantitative process and output indicators, 3) a before and after cross-sectional survey among post-partum women, 4) qualitative interviews with all opinion leaders, and 5) qualitative interviews with postpartum women and health workers in two healthcare facilities per country, as part of a case study approach. We foresee that the QUALI-DEC process evaluation will generate valuable information that will improve interpretation of the effectiveness evaluation. At the policy level, we anticipate that important lessons and methodological insights will be drawn, with application to other settings and stakeholders looking to implement complex interventions aiming to improve maternal and newborn health and wellbeing. Trial registration : ISRCTN67214403.

Objectives: Daily calcium supplements are recommended for pregnant women from 20 weeks' gestation to prevent pre-eclampsia in populations with low dietary calcium intake. We aimed to improve understanding of barriers and facilitators for calcium supplement intake during pregnancy to prevent pre-eclampsia., Design: Mixed-method systematic review, with confidence assessed using the Grading of Recommendations, Assessment, Development and Evaluations-Confidence in the Evidence from Reviews of Qualitative research approach., Data Sources: MEDLINE and EMBASE (via Ovid), CINAHL and Global Health (via EBSCO) and grey literature databases were searched up to 17 September 2022., Eligibility Criteria: We included primary qualitative, quantitative and mixed-methods studies reporting implementation or use of calcium supplements during pregnancy, excluding calcium fortification and non-primary studies. No restrictions were imposed on settings, language or publication date., Data Extraction and Synthesis: Two independent reviewers extracted data and assessed risk of bias. We analysed the qualitative data using thematic synthesis, and quantitative findings were thematically mapped to qualitative findings. We then mapped the results to behavioural change frameworks to identify barriers and facilitators., Results: Eighteen reports from nine studies were included in this review. Women reported barriers to consuming calcium supplements included limited knowledge about calcium supplements and pre-eclampsia, fears and experiences of side effects, varying preferences for tablets, dosing, working schedules, being away from home and taking other supplements. Receiving information regarding pre-eclampsia and safety of calcium supplement use from reliable sources, alternative dosing options, supplement reminders, early antenatal care, free supplements and support from families and communities were reported as facilitators. Healthcare providers felt that consistent messaging about benefits and risks of calcium, training, and ensuring adequate staffing and calcium supply is available would be able to help them in promoting calcium., Conclusion: Relevant stakeholders should consider the identified barriers and facilitators when formulating interventions and policies on calcium supplement use. These review findings can inform implementation to ensure effective and equitable provision and scale-up of calcium interventions., Prospero Registration Number: CRD42021239143., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Introduction: Low dietary calcium intake is a risk factor for pre-eclampsia, a major contributor to maternal and perinatal mortality and morbidity worldwide. Calcium supplementation can prevent pre-eclampsia in women with low dietary calcium. However, the optimal dose and timing of calcium supplementation are not known. We plan to undertake an individual participant data (IPD) meta-analysis of randomised trials to determine the effects of various calcium supplementation regimens in preventing pre-eclampsia and its complications and rank these by effectiveness. We also aim to evaluate the cost-effectiveness of calcium supplementation to prevent pre-eclampsia., Methods and Analysis: We will identify randomised trials on calcium supplementation before and during pregnancy by searching major electronic databases including Embase, CINAHL, MEDLINE, CENTRAL, PubMed, Scopus, AMED, LILACS, POPLINE, AIM, IMSEAR, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform, without language restrictions, from inception to February 2022. Primary researchers of the identified trials will be invited to join the International Calcium in Pregnancy Collaborative Network and share their IPD. We will check each study's IPD for consistency with the original authors before standardising and harmonising the data. We will perform a series of one-stage and two-stage IPD random-effect meta-analyses to obtain the summary intervention effects on pre-eclampsia with 95% CIs and summary treatment-covariate interactions (maternal risk status, dietary intake, timing of intervention, daily dose of calcium prescribed and total intake of calcium). Heterogeneity will be summarised using tau 2 , I 2 and 95% prediction intervals for effect in a new study. Sensitivity analysis to explore robustness of statistical and clinical assumptions will be carried out. Minor study effects (potential publication bias) will be investigated using funnel plots. A decision analytical model for use in low-income and middle-income countries will assess the cost-effectiveness of calcium supplementation to prevent pre-eclampsia., Ethics and Dissemination: No ethical approvals are required. We will store the data in a secure repository in an anonymised format. The results will be published in peer-reviewed journals., Prospero Registration Number: CRD42021231276., Competing Interests: Competing interests: None declared., (© World Health Organization 2023. Licensee BMJ.)

Women's fear and uncertainty about vaginal delivery and lack of empowerment in decision-making generate decision conflict and is one of the main determinants of high caesarean section rates in low- and middle-income countries (LMICs). This study aims to develop a decision analysis tool (DAT) to help pregnant women make an informed choice about the planned mode of delivery and to evaluate its acceptability in Vietnam, Thailand, Argentina, and Burkina Faso. The DAT targets low-risk pregnant women with a healthy, singleton foetus, without any medical or obstetric disorder, no previous caesarean scarring, and eligibility for labour trials. We conducted a systematic review to determine the short- and long-term maternal and offspring risks and benefits of planned caesarean section compared to planned vaginal delivery. We carried out individual interviews and focus group discussions with key informants to capture informational needs for decision-making, and to assess the acceptability of the DAT in participating hospitals. The DAT meets 20 of the 22 Patient Decision Aid Standards for decision support. It includes low- to moderate-certainty evidence-based information on the risks and benefits of both modes of birth, and helps pregnant women clarify their personal values. It has been well accepted by women and health care providers. Adaptations have been made in each country to fit the context and to facilitate its implementation in current practice, including the development of an App. DAT is a simple method to improve communication and facilitate shared decision-making for planned modes of birth. It is expected to build trust and foster more effective, satisfactory dialogue between pregnant women and providers. It can be easily adapted and updated as new evidence emerges. We encourage further studies in LMICs to assess the impact of DAT on quality decision-making for the appropriate use of caesarean section in these settings., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Dumont et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: To compare the risk of severe adverse maternal outcomes (SMO) and neonatal outcomes (SNO) and analyse their maternal correlates in adolescent mother-newborn and young mother-newborn dyads in secondary and tertiary care users in Latin America., Methods: We performed a secondary analysis of the WHO Multicountry Survey on Maternal and Newborn Health database in 83 secondary and tertiary hospitals in seven countries in Latin America. We constructed a composite indicator of both SMO and SNO and estimated odds ratios (OR) comparing adolescent mothers (aged 12-19) with young mothers (aged 20-24). Our unit of analysis was the mother-newborn dyad., Results: We found that the combination of SMO and SNO was three times more likely in adolescent mother as compared to young mother dyads (OR 3.56; 95% CI 1.67-7.59). SNO either alone or in combination with SMO were more likely in adolescents aged 12 to 16 than in young women (OR 1.27 and 4.87, respectively)., Conclusions for Practice: Adolescent mothers and their newborns are at an increased risk of severe adverse outcomes during child birth and in the first week postpartum compared to young mother dyads, especially young adolescents. Focusing on the dyad as a whole may facilitate a step towards integrated care which maximizes the health benefits of both mother and newborn. Continued efforts are needed to improve health care and prevention initiatives directed towards adolescent women and their newborns in Latin America., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Obstetric haemorrhage continues to be a leading cause of maternal mortality, contributing to more than a quarter of the 2,443,000 maternal deaths reported between 2003 and 2009. During this period, about 70% of the haemorrhagic deaths occurred postpartum. In addition to other identifiable risk factors for greater postpartum blood loss, the duration of the third stage of labour (TSL) seems to be important, as literature shows that a longer TSL can be associated with more blood loss. To better describe the association between the duration of TSL and postpartum blood loss in women receiving active management of third stage of labour (AMTSL), this secondary analysis of the WHO CHAMPION trial data has been conducted., Methods: This was a secondary analysis of the WHO CHAMPION trial conducted in twenty-three sites in ten countries. We studied the association between the TSL duration and blood loss in the sub cohort of women from the CHAMPION trial (all of whom received AMTSL), with TSL upto 60 min and no interventions for postpartum haemorrhage. We used a general linear model to fit blood loss as a function of TSL duration on the log scale, arm and center, using a normal distribution and the log link function. We showed this association separately for oxytocin and for Heat stable (HS) carbetocin., Results: For the 10,040 women analysed, blood loss rose steeply with third stage duration in the first 10 min, but more slowly after 10 min. This trend was observed for both Oxytocin and HS carbetocin and the difference in the trends for both drugs was not statistically significant (p-value = 0.2070)., Conclusions: There was a positive association between postpartum blood loss and TSL duration with either uterotonic. Blood loss rose steeply with TSL duration until 10 min, and more slowly after 10 min. Study registration The main trial was registered with Australian New Zealand Clinical Trials Registry ACTRN12614000870651 and Clinical Trial Registry of India CTRI/2016/05/006969., (© 2021. The Author(s).)

Introduction: Abortion-related complications are a significant cause of morbidity and mortality among women in many Latin American and Caribbean (LAC) countries. The objective of this study was to characterise abortion-related complication severity, describe the management of these complications and report women's experiences with abortion care in selected countries of the Americas region., Methods: This is a cross-sectional study of 70 health facilities across six countries in the region. We collected data on women's characteristics including socio-demographics, obstetric history, clinical information, management procedures and using Audio Computer-Assisted Self-Interviewing (ACASI) survey the experience of abortion care. Descriptive bivariate analysis was performed for women's characteristics, management of complications and reported experiences of abortion care by severity of complications, organised in five hierarchical mutually exclusive categories based on indicators present at assessment. Generalised linear estimation models were used to assess the association between women's characteristics and severity of complications., Results: We collected data on 7983 women with abortion-related complications. Complications were classified as mild (46.3%), moderate (49.5%), potentially life-threatening (3.1%), near-miss cases (1.1%) and deaths (0.2%). Being single, having a gestational age of ≥13 weeks and having expelled products of conception before arrival at the facility were significantly associated with experiencing severe maternal outcomes compared with mild complications.Management of abortion-related complications included both uterotonics and uterine evacuation for two-thirds of the women while one-third received uterine evacuation only. Surgical uterine evacuation was performed in 93.2% (7437/7983) of women, being vacuum aspiration the most common one (5007/7437, 67.4%).Of the 327 women who completed the ACASI survey, 16.5% reported having an induced abortion, 12.5% of the women stated that they were not given explanations regarding their care nor were able to ask questions during their examination and treatment with percentages increasing with the severity of morbidity., Conclusions: This is one of the first studies using a standardised methodology to measure severity of abortion-related complications and women's experiences with abortion care in LAC. Results aim to inform policies and programmes addressing sexual and reproductive rights and health in the region., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Background: The safety and efficacy of antenatal glucocorticoids in women in low-resource countries who are at risk for preterm birth are uncertain., Methods: We conducted a multicountry, randomized trial involving pregnant women between 26 weeks 0 days and 33 weeks 6 days of gestation who were at risk for preterm birth. The participants were assigned to intramuscular dexamethasone or identical placebo. The primary outcomes were neonatal death alone, stillbirth or neonatal death, and possible maternal bacterial infection; neonatal death alone and stillbirth or neonatal death were evaluated with superiority analyses, and possible maternal bacterial infection was evaluated with a noninferiority analysis with the use of a prespecified margin of 1.25 on the relative scale., Results: A total of 2852 women (and their 3070 fetuses) from 29 secondary- and tertiary-level hospitals across Bangladesh, India, Kenya, Nigeria, and Pakistan underwent randomization. The trial was stopped for benefit at the second interim analysis. Neonatal death occurred in 278 of 1417 infants (19.6%) in the dexamethasone group and in 331 of 1406 infants (23.5%) in the placebo group (relative risk, 0.84; 95% confidence interval [CI], 0.72 to 0.97; P = 0.03). Stillbirth or neonatal death occurred in 393 of 1532 fetuses and infants (25.7%) and in 444 of 1519 fetuses and infants (29.2%), respectively (relative risk, 0.88; 95% CI, 0.78 to 0.99; P = 0.04); the incidence of possible maternal bacterial infection was 4.8% and 6.3%, respectively (relative risk, 0.76; 95% CI, 0.56 to 1.03). There was no significant between-group difference in the incidence of adverse events., Conclusions: Among women in low-resource countries who were at risk for early preterm birth, the use of dexamethasone resulted in significantly lower risks of neonatal death alone and stillbirth or neonatal death than the use of placebo, without an increase in the incidence of possible maternal bacterial infection. (Funded by the Bill and Melinda Gates Foundation and the World Health Organization; Australian and New Zealand Clinical Trials Registry number, ACTRN12617000476336; Clinical Trials Registry-India number, CTRI/2017/04/008326.)., (Copyright © 2020 Massachusetts Medical Society.)

Background: While cesarean sections (CSs) are a life-saving intervention, an increasing number are performed without medical reasons in low- and middle-income countries (LMICs). Unnecessary CS diverts scarce resources and thereby reduces access to healthcare for women in need. Argentina, Burkina Faso, Thailand, and Vietnam are committed to reducing unnecessary CS, but many individual and organizational factors in healthcare facilities obstruct this aim. Nonclinical interventions can overcome these barriers by helping providers improve their practices and supporting women's decision-making regarding childbirth. Existing evidence has shown only a modest effect of single interventions on reducing CS rates, arguably because of the failure to design multifaceted interventions effectively tailored to the context. The aim of this study is to design, adapt, and test a multifaceted intervention for the appropriate use of CS in Argentina, Burkina Faso, Thailand, and Vietnam., Methods: We designed an intervention (QUALIty DECision-making-QUALI-DEC) with four components: (1) opinion leaders at heathcare facilities to improve adherence to best practices among clinicians, (2) CS audits and feedback to help providers identify potentially avoidable CS, (3) a decision analysis tool to help women make an informed decision on the mode of birth, and (4) companionship to support women during labor. QUALI-DEC will be implemented and evaluated in 32 hospitals (8 sites per country) using a pragmatic hybrid effectiveness-implementation design to test our implementation strategy, and information regarding its impact on relevant maternal and perinatal outcomes will be gathered. The implementation strategy will involve the participation of women, healthcare professionals, and organizations and account for the local environment, needs, resources, and social factors in each country., Discussion: There is urgent need for interventions and implementation strategies to optimize the use of CS while improving health outcomes and satisfaction in LMICs. This can only be achieved by engaging all stakeholders involved in the decision-making process surrounding birth and addressing their needs and concerns. The study will generate robust evidence about the effectiveness and the impact of this multifaceted intervention. It will also assess the acceptability and scalability of the intervention and the capacity for empowerment among women and providers alike., Trial Registration: ISRCTN67214403.

Objective: To characterise the occurrence of fever (≥38.0°C) after treatment for post-partum haemorrhage (PPH) with sublingual misoprostol 800 mcg in Latin America, where elevated rates of misoprostol's thermoregulatory effects and recipients' increased susceptibility to high fever have been documented., Methods: A prospective observational study in hospitals in Argentina enrolled consenting women with atonic PPH after vaginal delivery, eligible to receive misoprostol. Corporal temperature was assessed at 30, 60, 90 and 120 min post-treatment; other effects were recorded. The incidence of high fever ≥ 40.0°C (primary outcome) was compared to the rate observed previously in Ecuador. Logistic regressions were performed to identify clinical and population-based predictors of misoprostol-induced fever., Results: Transient shivering and fever were experienced by 75.5% (37/49) of treated participants and described as acceptable by three-quarters of women interviewed (35/47). The high fever rate was 12.2% (6/49), [95% Confidence Interval (CI) 4.6, 24.8], compared to Ecuador's rate following misoprostol treatment (35.6% (58/163) [95% CI 28.3, 43.5], P = 0.002). Significant predictors of misoprostol-induced fever (model dependent) were as follows: pre-delivery haemoglobin < 11.0g/dl, rapid placental expulsion, and higher age of the woman. No serious outcomes were reported prior to discharge., Conclusions: Misoprostol to treat PPH in Argentina resulted in a significantly lower rate of high fever than in Ecuador, although both are notably higher than rates seen elsewhere. A greater understanding of misoprostol's side effects and factors involved in their occurrence, including genetics, will help alleviate concerns. The onset of shivering may be the simplest way to know if fever can also be expected., (© 2020 The Authors Tropical Medicine & International Health Published by John Wiley & Sons Ltd.)

Objective: We assessed the impact of intravenous (IV) infusion versus intramuscular (IM) oxytocin on postpartum blood loss and rates of postpartum hemorrhage (PPH) when administered during the third stage of labor. While oxytocin is recommended for prevention of PPH, few double-blind studies have compared outcomes by routes of administration., Methods: A double-blind, placebo-controlled randomized trial was conducted at a hospital in Argentina. Participants were assigned to receive 10 IU oxytocin via IV infusion or IM injection and a matching saline ampoule for the other route after vaginal birth. Blood loss was measured using a calibrated receptacle for a 1-hour minimum. Shock index (SI) was also calculated, based on vital signs measurements, and additional interventions were recorded. Primary outcomes included: the frequency of blood loss ≥500ml and mean blood loss., Results: 239 (IV infusion) and 241 (IM) women were enrolled with comparable baseline characteristics. Mean blood loss was 43ml less in the IV infusion group (p = 0.161). Rates of blood loss ≥500ml were similar (IV infusion = 21%; IM = 24%, p = 0.362). Women in the IV infusion group received significantly fewer additional uterotonics (5%), than women in the IM group (12%, p = 0.007). Women with PPH in the IM group experienced a larger increase in SI after delivery, which may have influenced recourse to additional interventions., Conclusions: The route of oxytocin administration for PPH prevention did not significantly impact measured blood loss after vaginal birth. However, differences were observed in recourse to additional uterotonics, favoring IV infusion over IM. In settings where IV lines are routinely placed, oxytocin infusion may be preferable to IM injection., Competing Interests: The authors have declared that no competing interests exist.

Background: Almost 358,000 women die each year in childbirth, mainly in low-income countries. More than half of all maternal deaths occur within 24 hours of giving birth; severe bleeding in the postpartum period is the single most important cause. Depending on the rate of blood loss and other factors, such as pre-existing anaemia, untreated postpartum haemorrhage (PPH) can lead to hypovolaemic shock, multi-organ dysfunction, and maternal death, within two to six hours.This review investigated different methods for estimating blood loss. The most common method of measuring blood loss during the third stage of labour is visual estimation, during which the birth attendant makes a quantitative or semi-quantitative estimate of the amount of blood lost. In direct blood collection, all blood lost during the third stage of labour (except for the placenta and membranes) is contained in a disposable, funnelled, plastic collector bag, which is attached to a plastic sheet, and placed under the woman's buttocks. When the bleeding stops, there are two options: the bag can be weighed (also called gravimetric technique), or the bag can be calibrated, allowing for a direct measurement. A more precise measurement of blood loss is haemoglobin concentration (Hb) in venous blood sampling and spectrophotometry. With the dye dilution technique, a known quantity of dye is injected into the vein and its plasmatic concentration is monitored after the uterus stops bleeding. Using nuclear medicine, a radioactive tracer is injected, and its concentration is monitored after the uterus stops bleeding. Although hypothetically, these advanced methods could provide a better quantification of blood loss, they are difficult to perform and are not accessible in most settings., Objectives: To evaluate the effect of alternative methods to estimate blood loss during the third stage of labour, to help healthcare providers reduce the adverse consequences of postpartum haemorrhage after vaginal birth., Search Methods: We searched Cochrane Pregnancy and Childbirth's Trials Register (2 February 2018), ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP; 21 March 2018), and reference lists of retrieved studies., Selection Criteria: All randomised trials, including cluster-randomised trials, evaluating methods for estimating blood loss after vaginal birth., Data Collection and Analysis: Two review authors independently assessed trials for inclusion and risk of bias, extracted data, and checked them for accuracy., Main Results: The search retrieved 62 reports in total. Of these, we assessed 12 reports in full, corresponding to six trials. We included three trials and excluded one; two trials are ongoing.The included trials were conducted in hospital settings. Two trials were conducted in India; the third trial was a large cluster-randomised trial, which took place in 13 European countries. Overall, we judged the included trials to be at a low risk of bias. One study evaluated the use of calibrated drapes versus visual estimation, another evaluated the use of calibrated drapes versus the gravimetric technique (weight of blood-soaked materials), therefore, we were unable to pool the data from the two studies. The third study did not measure any of the outcomes of interest, so did not contribute data to the analyses.Direct measurement using calibrated drapes versus visual estimationOne cluster-randomised controlled trial in 13 western European countries, with over 25,000 women, examined this comparison.The trial did not report on postpartum anaemia (defined as Hb lower than 9 mg/dL), blood loss greater than 500 mL, or maternal infection.Moderate-quality evidence suggests there is probably little or no difference between groups in: severe morbidity (coagulopathy, organ failure, intensive care unit admission; adjusted risk ratio (RR) 0.82, 95% confidence interval (CI) 0.48 to 1.39); the risk of blood transfusion (adjusted RR 0.82, 95% CI 0.46 to 1.46); the use of plasma expanders (adjusted RR 0.77, 95% CI 0.42 to 1.42); and the use of therapeutic uterotonics (adjusted RR 0.87, 95% CI 0.42 to 1.76).Direct measurement using calibrated drapes (Excellent BRASSS-V Drape™) versus gravimetric techniqueOne randomised controlled trial in India, with 900 women, examined this comparison.The trial did not report on postpartum anaemia (defined as Hb lower than 9 mg/dL), severe morbidity, or maternal infection.High-quality evidence showed that using calibrated drapes improved the detection of blood loss greater than 500 mL when compared with the gravimetric technique (RR 1.86, 95% CI 1.11 to 3.11). Low-quality evidence suggests there may be little or no difference in the risk of blood transfusion between the two groups (RR 1.00, 95% CI 0.06 to 15.94), or in the use of plasma expanders, reported as intravenous fluids given for PPH treatment (RR 0.67; 95% CI 0.19 to 2.35). High-quality evidence showed little or no difference in the use of therapeutic uterotonics (RR 1.01, 95% CI 0.90 to 1.13), but the use of therapeutic uterotonics was extremely high in both arms of the study (57% and 56%)., Authors' Conclusions: Overall, the evidence in this review is insufficient to support the use of one method over another for blood loss estimation after vaginal birth. In general, the quality of evidence for our predefined outcomes ranged from low to high quality, with downgrading decisions due to imprecision. The included trials did not report on many of our primary and secondary outcomes.In trials that evaluate methods for estimating blood loss during vaginal birth, we believe it is important to measure their impact on clinical maternal and neonatal outcomes, along with their diagnostic accuracy. This body of knowledge needs further, well designed, appropriately powered, randomised controlled trials that correlate blood loss with relevant clinical outcomes, such as those listed in this review.

Background: Postpartum hemorrhage is the most common cause of maternal death. Oxytocin is the standard therapy for the prevention of postpartum hemorrhage, but it requires cold storage, which is not available in many countries. In a large trial, we compared a novel formulation of heat-stable carbetocin with oxytocin., Methods: We enrolled women across 23 sites in 10 countries in a randomized, double-blind, noninferiority trial comparing intramuscular injections of heat-stable carbetocin (at a dose of 100 μg) with oxytocin (at a dose of 10 IU) administered immediately after vaginal birth. Both drugs were kept in cold storage (2 to 8°C) to maintain double-blinding. There were two primary outcomes: the proportion of women with blood loss of at least 500 ml or the use of additional uterotonic agents, and the proportion of women with blood loss of at least 1000 ml. The noninferiority margins for the relative risks of these outcomes were 1.16 and 1.23, respectively., Results: A total of 29,645 women underwent randomization. The frequency of blood loss of at least 500 ml or the use of additional uterotonic agents was 14.5% in the carbetocin group and 14.4% in the oxytocin group (relative risk, 1.01; 95% confidence interval [CI], 0.95 to 1.06), a finding that was consistent with noninferiority. The frequency of blood loss of at least 1000 ml was 1.51% in the carbetocin group and 1.45% in the oxytocin group (relative risk, 1.04; 95% CI, 0.87 to 1.25), with the confidence interval crossing the margin of noninferiority. The use of additional uterotonic agents, interventions to stop bleeding, and adverse effects did not differ significantly between the two groups., Conclusions: Heat-stable carbetocin was noninferior to oxytocin for the prevention of blood loss of at least 500 ml or the use of additional uterotonic agents. Noninferiority was not shown for the outcome of blood loss of at least 1000 ml; low event rates for this outcome reduced the power of the trial. (Funded by Merck Sharpe & Dohme; CHAMPION Australian New Zealand Clinical Trials Registry number, ACTRN12614000870651 ; EudraCT number, 2014-004445-26 ; and Clinical Trials Registry-India number, CTRI/2016/05/006969 .).

[This corrects the article DOI: 10.1371/journal.pmed.1002220.].

Background: Some clinicians believe that routine episiotomy, a surgical cut of the vagina and perineum, will prevent serious tears during childbirth. On the other hand, an episiotomy guarantees perineal trauma and sutures., Objectives: To assess the effects on mother and baby of a policy of selective episiotomy ('only if needed') compared with a policy of routine episiotomy ('part of routine management') for vaginal births., Search Methods: We searched Cochrane Pregnancy and Childbirth's Trials Register (14 September 2016) and reference lists of retrieved studies., Selection Criteria: Randomised controlled trials (RCTs) comparing selective versus routine use of episiotomy, irrespective of parity, setting or surgical type of episiotomy. We included trials where either unassisted or assisted vaginal births were intended. Quasi-RCTs, trials using a cross-over design or those published in abstract form only were not eligible for inclusion in this review., Data Collection and Analysis: Two authors independently screened studies, extracted data, and assessed risk of bias. A third author mediated where there was no clear consensus. We observed good practice for data analysis and interpretation where trialists were review authors. We used fixed-effect models unless heterogeneity precluded this, expressed results as risk ratios (RR) and 95% confidence intervals (CI), and assessed the certainty of the evidence using GRADE., Main Results: This updated review includes 12 studies (6177 women), 11 in women in labour for whom a vaginal birth was intended, and one in women where an assisted birth was anticipated. Two were trials each with more than 1000 women (Argentina and the UK), and the rest were smaller (from Canada, Germany, Spain, Ireland, Malaysia, Pakistan, Columbia and Saudi Arabia). Eight trials included primiparous women only, and four trials were in both primiparous and multiparous women. For risk of bias, allocation was adequately concealed and reported in nine trials; sequence generation random and adequately reported in three trials; blinding of outcomes adequate and reported in one trial, blinding of participants and personnel reported in one trial.For women where an unassisted vaginal birth was anticipated, a policy of selective episiotomy may result in 30% fewer women experiencing severe perineal/vaginal trauma (RR 0.70, 95% CI 0.52 to 0.94; 5375 women; eight RCTs; low-certainty evidence). We do not know if there is a difference for blood loss at delivery (an average of 27 mL less with selective episiotomy, 95% CI from 75 mL less to 20 mL more; two trials, 336 women, very low-certainty evidence). Both selective and routine episiotomy have little or no effect on infants with Apgar score less than seven at five minutes (four trials, no events; 3908 women, moderate-certainty evidence); and there may be little or no difference in perineal infection (RR 0.90, 95% CI 0.45 to 1.82, three trials, 1467 participants, low-certainty evidence).For pain, we do not know if selective episiotomy compared with routine results in fewer women with moderate or severe perineal pain (measured on a visual analogue scale) at three days postpartum (RR 0.71, 95% CI 0.48 to 1.05, one trial, 165 participants, very low-certainty evidence). There is probably little or no difference for long-term (six months or more) dyspareunia (RR1.14, 95% CI 0.84 to 1.53, three trials, 1107 participants, moderate-certainty evidence); and there may be little or no difference for long-term (six months or more) urinary incontinence (average RR 0.98, 95% CI 0.67 to 1.44, three trials, 1107 participants, low-certainty evidence). One trial reported genital prolapse at three years postpartum. There was no clear difference between the two groups (RR 0.30, 95% CI 0.06 to 1.41; 365 women; one trial, low certainty evidence). Other outcomes relating to long-term effects were not reported (urinary fistula, rectal fistula, and faecal incontinence). Subgroup analyses by parity (primiparae versus multiparae) and by surgical method (midline versus mediolateral episiotomy) did not identify any modifying effects. Pain was not well assessed, and women's preferences were not reported.One trial examined selective episiotomy compared with routine episiotomy in women where an operative vaginal delivery was intended in 175 women, and did not show clear difference on severe perineal trauma between the restrictive and routine use of episiotomy, but the analysis was underpowered., Authors' Conclusions: In women where no instrumental delivery is intended, selective episiotomy policies result in fewer women with severe perineal/vaginal trauma. Other findings, both in the short or long term, provide no clear evidence that selective episiotomy policies results in harm to mother or baby.The review thus demonstrates that believing that routine episiotomy reduces perineal/vaginal trauma is not justified by current evidence. Further research in women where instrumental delivery is intended may help clarify if routine episiotomy is useful in this particular group. These trials should use better, standardised outcome assessment methods.

Background: Perinatal mortality and morbidity continue to be major global health challenges strongly associated with prematurity and reduced fetal growth, an issue of further interest given the mounting evidence that fetal growth in general is linked to degrees of risk of common noncommunicable diseases in adulthood. Against this background, WHO made it a high priority to provide the present fetal growth charts for estimated fetal weight (EFW) and common ultrasound biometric measurements intended for worldwide use., Methods and Findings: We conducted a multinational prospective observational longitudinal study of fetal growth in low-risk singleton pregnancies of women of high or middle socioeconomic status and without known environmental constraints on fetal growth. Centers in ten countries (Argentina, Brazil, Democratic Republic of the Congo, Denmark, Egypt, France, Germany, India, Norway, and Thailand) recruited participants who had reliable information on last menstrual period and gestational age confirmed by crown-rump length measured at 8-13 wk of gestation. Participants had anthropometric and nutritional assessments and seven scheduled ultrasound examinations during pregnancy. Fifty-two participants withdrew consent, and 1,387 participated in the study. At study entry, median maternal age was 28 y (interquartile range [IQR] 25-31), median height was 162 cm (IQR 157-168), median weight was 61 kg (IQR 55-68), 58% of the women were nulliparous, and median daily caloric intake was 1,840 cal (IQR 1,487-2,222). The median pregnancy duration was 39 wk (IQR 38-40) although there were significant differences between countries, the largest difference being 12 d (95% CI 8-16). The median birthweight was 3,300 g (IQR 2,980-3,615). There were differences in birthweight between countries, e.g., India had significantly smaller neonates than the other countries, even after adjusting for gestational age. Thirty-one women had a miscarriage, and three fetuses had intrauterine death. The 8,203 sets of ultrasound measurements were scrutinized for outliers and leverage points, and those measurements taken at 14 to 40 wk were selected for analysis. A total of 7,924 sets of ultrasound measurements were analyzed by quantile regression to establish longitudinal reference intervals for fetal head circumference, biparietal diameter, humerus length, abdominal circumference, femur length and its ratio with head circumference and with biparietal diameter, and EFW. There was asymmetric distribution of growth of EFW: a slightly wider distribution among the lower percentiles during early weeks shifted to a notably expanded distribution of the higher percentiles in late pregnancy. Male fetuses were larger than female fetuses as measured by EFW, but the disparity was smaller in the lower quantiles of the distribution (3.5%) and larger in the upper quantiles (4.5%). Maternal age and maternal height were associated with a positive effect on EFW, particularly in the lower tail of the distribution, of the order of 2% to 3% for each additional 10 y of age of the mother and 1% to 2% for each additional 10 cm of height. Maternal weight was associated with a small positive effect on EFW, especially in the higher tail of the distribution, of the order of 1.0% to 1.5% for each additional 10 kg of bodyweight of the mother. Parous women had heavier fetuses than nulliparous women, with the disparity being greater in the lower quantiles of the distribution, of the order of 1% to 1.5%, and diminishing in the upper quantiles. There were also significant differences in growth of EFW between countries. In spite of the multinational nature of the study, sample size is a limiting factor for generalization of the charts., Conclusions: This study provides WHO fetal growth charts for EFW and common ultrasound biometric measurements, and shows variation between different parts of the world., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: GP is a WHO statistical consultant and has a contract to give statistical support to the Fetal Growth Study. GP has worked with WHO for 15 years and has a relationship with WHO, both paid (contracts) and unpaid. GP is also a good friend of many of the investigators involved in this study. LDP is a Board Member of the Perinatal Quality Foundation, a nonprofit organization related to the Society for Maternal Fetal Medicine. LDP has received research support from General Electric Medical Systems unrelated to fetal growth. LDP also lectures 1 or 2 times per year at an educational meeting supported by General Electric Medical Systems unrelated to fetal growth.

Background: Every year millions of women around the world suffer from pregnancy, childbirth and postpartum complications. Women who survive the most serious clinical conditions are regarded as to have experienced a severe acute maternal complication called maternal near miss (MNM). Information about MNM cases may complement the data collected through the analysis of maternal death, and was proposed as a helpful tool to identify strengths and weaknesses of health systems in relation to maternal health care. The purpose of this study is to evaluate the performance of a systematized form to detect severe maternal outcomes (SMO) in 20 selected maternity hospitals from Latin America (LAC)., Methods: Cross-sectional study. Data were obtained from analysis of hospital records for all women giving birth and all women who had a SMO in the selected hospitals. Univariate and multivariate adjusted logistic regression models were used to assess the predictive ability of different conditions to identify SMO cases. In parallel, external auditors were hired for reviewing and reporting the total number of discharges during the study period, in order to verify whether health professionals at health facilities identified all MNM and Potentially life-threatening condition (PLTC) cases., Results: Twenty hospitals from twelve LAC were initially included in the study and based on the level of coverage, 11 hospitals with a total of 3,196records were included for the final analysis. The incidence of SMO and MNM outcomes was 12.9 and 12.3 per 1,000 live births, respectively. The ratio of MNM to maternal death was 19 to 1, with a mortality index of 5.1 %. Both univariate and multivariate analysis showed a good performance for a number of clinical and laboratory conditions to predict a severe maternal outcome, however, their clinical relevance remains to be confirmed. Coherence between health professionals and external auditors to identify SMO was high (around 100 %)., Conclusions: The form tested, was well accepted by health professionals and was capable of identifying 100 % of MNM cases and more than 99 % of PLTC variables. Altered state of consciousness, oliguria, placenta accrete, pulmonary edema, and admission to Intensive Care Unit have a high (LR+ ≥80) capacity to anticipate a SMO.

Background: Postpartum haemorrhage (PPH) is the leading cause of maternal mortality in low-income countries and contributes to nearly a quarter of maternal deaths globally. The current available interventions for prevention of postpartum haemorrhage, oxytocin and carbetocin, are limited by their need for refrigeration to maintain potency, as the ability to maintain a cold chain across the drug distribution and storage network is inconsistent, thus restricting their use in countries with the highest burden of maternal mortality. We describe a randomized, double-blind non-inferiority trial comparing a newly developed room temperature stable formulation of carbetocin to the standard intervention (oxytocin) for the prevention of PPH after vaginal birth., Methods/design: Approximately 30,000 women delivering vaginally will be recruited across 22 centres in 10 countries. The primary objectives are to evaluate the non-inferiority of room temperature stable carbetocin (100 μg intramuscular) versus oxytocin (10 IU intramuscular) in the prevention of PPH and severe PPH after vaginal birth. The primary endpoints are blood loss ≥500 mL or the use of additional uterotonics (composite endpoint required by drug regulatory authorities) and blood loss ≥1,000 mL (WHO requirement). Non-inferiority will be assessed using a two-sided 95 % confidence interval for the relative risk of the above endpoints for room temperature stable carbetocin versus oxytocin. The upper limit of the two-sided 95 % confidence interval for the relative risk for the composite endpoint of blood loss ≥500 mL or the use of additional uterotonics, and for the endpoint of blood loss ≥1,000 mL, will be compared to a non-inferiority margin of 1.16 and 1.23, respectively. If the upper limit is below the corresponding margin, non-inferiority will have been demonstrated. The safety analysis will include all women receiving treatment. Safety and tolerability will be assessed by a review of adverse events, by conducting inferential testing with significance levels for between-group comparisons., Discussion: If the results of the study show that room temperature stable carbetocin is a safe and effective alternative to oxytocin, this could have a substantial impact on the prevention of postpartum haemorrhage and maternal survival worldwide., Trial Registration: ACTRN12614000870651 (14 August 2014).

Objective: To assess the accuracy of angiogenic biomarkers to predict pre-eclampsia., Design: Prospective multicentre study. From 2006 to 2009, 5121 pregnant women with risk factors for pre-eclampsia (nulliparity, diabetes, previous pre-eclampsia, chronic hypertension) from Argentina, Colombia, Peru, India, Italy, Kenya, Switzerland and Thailand had their serum tested for sFlt-1, PlGF and sEng levels and their urine for PlGF levels at ⩽20, 23-27 and 32-35weeks' gestation (index tests, results blinded from carers). Women were monitored for signs of pre-eclampsia, diagnosed by systolic blood pressure ⩾140mmHg and/or diastolic blood pressure ⩾90mmHg, and proteinuria (protein/creatinine ratio ⩾0.3, protein ⩾1g/l, or one dipstick measurement ⩾2+) appearing after 20weeks' gestation. Early pre-eclampsia was defined when these signs appeared ⩽34weeks' gestation., Main Outcome Measure: Pre-eclampsia., Results: Pre-eclampsia was diagnosed in 198 of 5121 women tested (3.9%) of whom 47 (0.9%) developed it early. The median maternal serum concentrations of index tests were significantly altered in women who subsequently developed pre-eclampsia than in those who did not. However, the area under receiver operating characteristics curve at ⩽20weeks' gestation were closer to 0.5 than to 1.0 for all biomarkers both for predicting any pre-eclampsia or at ⩽34weeks' gestation. The corresponding sensitivity, specificity and likelihood ratios were poor. Multivariable models combining sEng with clinical features slightly improved the prediction capability., Conclusions: Angiogenic biomarkers in first half of pregnancy do not perform well enough in predicting the later development of pre-eclampsia., (Copyright © 2015. Published by Elsevier B.V.)

Background: The number of visits for antenatal (prenatal) care developed without evidence of how many visits are necessary. The content of each visit also needs evaluation., Objectives: To compare the effects of antenatal care programmes with reduced visits for low-risk women with standard care., Search Methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (23 March 2015), reference lists of articles and contacted researchers in the field., Selection Criteria: Randomised trials comparing a reduced number of antenatal visits, with or without goal-oriented care, versus standard care., Data Collection and Analysis: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked for accuracy. We assessed studies for risk of bias and graded the quality of the evidence., Main Results: We included seven trials (more than 60,000 women): four in high-income countries with individual randomisation; three in low- and middle-income countries with cluster randomisation (clinics as the unit of randomisation). Most of the data included in the review came from the three large, well-designed cluster-randomised trials that took place in Argentina, Cuba, Saudi Arabia, Thailand and Zimbabwe. All results have been adjusted for the cluster design effect. All of the trials were at some risk of bias as blinding of women and staff was not feasible with this type of intervention. For primary outcomes, evidence was graded as being of moderate or low quality, with downgrading decisions due to risks of bias and imprecision of effects.The number of visits for standard care varied, with fewer visits in low- and middle- income country trials. In studies in high-income countries, women in the reduced visits groups, on average, attended between 8.2 and 12 times. In low- and middle- income country trials, many women in the reduced visits group attended on fewer than five occasions, although in these trials the content as well as the number of visits was changed, so as to be more 'goal-oriented'.Perinatal mortality was increased for those randomised to reduced visits rather than standard care, and this difference was borderline for statistical significance (risk ratio (RR) 1.14; 95% confidence interval (CI) 1.00 to 1.31; five trials, 56,431 babies; moderate-quality evidence). In the subgroup analysis, for high-income countries the number of deaths was small (32/5108), and there was no clear difference between the groups (RR 0.90; 95% CI 0.45 to 1.80, two trials); for low- and middle-income countries perinatal mortality was significantly higher in the reduced visits group (RR 1.15; 95% CI 1.01 to 1.32, three trials).There was no clear difference between groups for our other primary outcomes: maternal death (RR 1.13, 95%CI 0.50 to 2.57, three cluster-randomised trials, 51,504 women, low-quality evidence); hypertensive disorders of pregnancy (various definitions including pre-eclampsia) (RR 0.95, 95% CI 0.80 to 1.12, six studies, 54,108 women, low-quality evidence); preterm birth (RR 1.02, 95% CI 0.94 to 1.11; seven studies, 53,661 women, moderate-quality evidence); and small-for-gestational age (RR 0.99, 95% CI 0.91 to 1.09, four studies 43,045 babies, moderate-quality evidence).Reduced visits were associated with a reduction in admission to neonatal intensive care that was borderline for significance (RR 0.89; 95% CI 0.79 to 1.02, five studies, 43,048 babies, moderate quality evidence). There were no clear differences between the groups for the other secondary clinical outcomes.Women in all settings were less satisfied with the reduced visits schedule and perceived the gap between visits as too long. Reduced visits may be associated with lower costs., Authors' Conclusions: In settings with limited resources where the number of visits is already low, reduced visits programmes of antenatal care are associated with an increase in perinatal mortality compared to standard care, although admission to neonatal intensive care may be reduced. Women prefer the standard visits schedule. Where the standard number of visits is low, visits should not be reduced without close monitoring of fetal and neonatal outcome.

Objective: To test whether the proposed features of the Obstetric Transition Model-a theoretical framework that may explain gradual changes that countries experience as they eliminate avoidable maternal mortality-are observed in a large, multicountry, maternal and perinatal health database; and to discuss the dynamic process of maternal mortality reduction using this model as a theoretical framework., Methods: This was a secondary analysis of a cross-sectional study by the World Health Organization that collected information on more than 300 000 women who delivered in 359 health facilities in 29 countries in Africa, Asia, Latin America, and the Middle East, during a 2-4-month period in 2010-2011. The ratios of Potentially Life-Threatening Conditions, Severe Maternal Outcomes, Maternal Near Miss, and Maternal Death were estimated and stratified by stages of obstetric transition. The characteristics of each stage are defined., Results: Data from 314 623 women showed that female fertility, indirectly estimated by parity, was higher in countries at a lower obstetric transition stage, ranging from a mean of 3 children in Stage II to 1.8 children in Stage IV. Medicalization increased with obstetric transition stage. In Stage IV, women had 2.4 times the cesarean deliveries (15.3% in Stage II and 36.7% in Stage IV) and 2.6 times the labor inductions (7.1% in Stage II and 18.8% in Stage IV) as women in Stage II. The mean age of primiparous women also increased with stage. The occurrence of uterine rupture had a decreasing trend, dropping by 5.2 times, from 178 to 34 cases per 100 000 live births, as a country transitioned from Stage II to IV., Conclusions: This analysis supports the concept of obstetric transition using multicountry data. The Obstetric Transition Model could provide justification for customizing strategies for reducing maternal mortality according to a country's stage in the obstetric transition.

Background: Despite the global burden of morbidity and mortality associated with preterm birth, little evidence is available for use of antenatal corticosteroids and tocolytic drugs in preterm births in low-income and middle-income countries. We analysed data from the WHO Multicountry Survey on Maternal and Newborn Health (WHOMCS) to assess coverage for these interventions in preterm deliveries., Methods: WHOMCS is a facility-based, cross-sectional survey database of birth outcomes in 359 facilities in 29 countries, with data collected prospectively from May 1, 2010, to Dec 31, 2011. For this analysis, we included deliveries after 22 weeks' gestation and we excluded births that occurred outside a facility or quicker than 3 h after arrival. We calculated use of antenatal corticosteroids in women who gave birth between 26 and 34 weeks' gestation, when antenatal corticosteroids are known to be most beneficial. We also calculated use in women at 22-25 weeks' and 34-36 weeks' gestation. We assessed tocolytic drug use, with and without antenatal corticosteroids, in spontaneous, uncomplicated preterm deliveries at 26-34 weeks' gestation., Findings: Of 303,842 recorded deliveries after 22 weeks' gestation, 17,705 (6%) were preterm. 3900 (52%) of 7547 women who gave birth at 26-34 weeks' gestation, 94 (19%) of 497 women who gave birth at 22-25 weeks' gestation, and 2276 (24%) of 9661 women who gave birth at 35-36 weeks' gestation received antenatal corticosteroids. Rates of antenatal corticosteroid use varied between countries (median 54%, range 16-91%; IQR 30-68%). Of 4677 women who were potentially eligible for tocolysis drugs, 1276 (27%) were treated with bed rest or hydration and 2248 (48%) received no treatment. β-agonists alone (n=346, 7%) were the most frequently used tocolytic drug. Only 848 (18%) of potentially eligible women received both a tocolytic drug and antenatal corticosteroids., Interpretation: Use of interventions was generally poor, despite evidence for their benefit for newborn babies. A substantial proportion of antenatal corticosteroid use occurred at gestational ages at which benefit is controversial, and use of less effective or potentially harmful tocolytic drugs was common. Implementation research and contextualised health policies are needed to improve drug availability and increase compliance with best obstetric practice., Funding: UNDP-UNFPA-UNICEF-WHO-World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP); WHO; USAID; Ministry of Health, Labour and Welfare of Japan; Gynuity Health Projects., (Copyright © 2014 World Health Organization. Published by Elsevier Ltd/Inc/BV. All rights reserved. Published by Elsevier Ltd. All rights reserved.)

Background: Maternal mortality has declined by nearly half since 1990, but over a quarter million women still die every year of causes related to pregnancy and childbirth. Maternal-health related targets are falling short of the 2015 Millennium Development Goals and a post-2015 Development Agenda is emerging. In connection with this, setting global research priorities for the next decade is now required., Methods: We adapted the methods of the Child Health and Nutrition Research Initiative (CHNRI) to identify and set global research priorities for maternal and perinatal health for the period 2015 to 2025. Priority research questions were received from various international stakeholders constituting a large reference group, and consolidated into a final list of research questions by a technical working group. Questions on this list were then scored by the reference working group according to five independent and equally weighted criteria. Normalized research priority scores (NRPS) were calculated, and research priority questions were ranked accordingly., Results: A list of 190 priority research questions for improving maternal and perinatal health was scored by 140 stakeholders. Most priority research questions (89%) were concerned with the evaluation of implementation and delivery of existing interventions, with research subthemes frequently concerned with training and/or awareness interventions (11%), and access to interventions and/or services (14%). Twenty-one questions (11%) involved the discovery of new interventions or technologies., Conclusions: Key research priorities in maternal and perinatal health were identified. The resulting ranked list of research questions provides a valuable resource for health research investors, researchers and other stakeholders. We are hopeful that this exercise will inform the post-2015 Development Agenda and assist donors, research-policy decision makers and researchers to invest in research that will ultimately make the most significant difference in the lives of mothers and babies.

Background: In 2006 WHO presented the infant and child growth charts suggested for universal application. However, major determinants for perinatal outcomes and postnatal growth are laid down during antenatal development. Accordingly, monitoring fetal growth in utero by ultrasonography is important both for clinical and scientific reasons. The currently used fetal growth references are derived mainly from North American and European population and may be inappropriate for international use, given possible variances in the growth rates of fetuses from different ethnic population groups. WHO has, therefore, made it a high priority to establish charts of optimal fetal growth that can be recommended worldwide., Methods: This is a multi-national study for the development of fetal growth standards for international application by assessing fetal growth in populations of different ethnic and geographic backgrounds. The study will select pregnant women of high-middle socioeconomic status with no obvious environmental constraints on growth (adequate nutritional status, non-smoking), and normal pregnancy history with no complications likely to affect fetal growth. The study will be conducted in centres from ten developing and industrialized countries: Argentina, Brazil, Democratic Republic of Congo, Denmark, Egypt, France, Germany, India, Norway, and Thailand. At each centre, 140 pregnant women will be recruited between 8 + 0 and 12 + 6 weeks of gestation. Subsequently, visits for fetal biometry will be scheduled at 14, 18, 24, 28, 32, 36, and 40 weeks (+/- 1 week) to be performed by trained ultrasonographers.The main outcome of the proposed study will be the development of fetal growth standards (either global or population specific) for international applications., Discussion: The data from this study will be incorporated into obstetric practice and national health policies at country level in coordination with the activities presently conducted by WHO to implement the use of the Child Growth Standards.

Background: Mode of delivery remains a topic of debate in vertex/non-vertex twin pregnancies. We used the WHO Global Survey dataset to determine the risk of adverse maternal/perinatal outcomes associated with presentation of the second twin, following vaginal delivery of a vertex first twin., Methods: We analysed a derived dataset of twin pregnancies ≥ 32 weeks gestation where the first twin was vertex and delivered vaginally. Maternal, delivery and neonatal characteristics and adverse outcomes were reported by presentation of the second twin. Logistic regression models (adjusted for maternal and perinatal confounders, mode of delivery and region) were developed to determine odds of adverse outcomes associated with presentation., Results: 1,424 twin pregnancies were included, 25.9% of these had a non-vertex second twin and Caesarean was more common in non-vertex presentations (6.2% vs 0.9%, p < 0.001). While the odds of Apgar < 7 at 5 minutes were higher in non-vertex presenting second twins (16.0% vs 11.4%, AOR 1.42 95% CI 1.01-2.00), the odds of maternal ICU admission (4.6% vs 1.7%, AOR 1.30, 95% CI 0.88-1.94), blood transfusion (6.0% vs 3.4%, AOR 1.23, 95% CI 0.67-2.25), stillbirth (7.6% vs 4.7%, AOR 1.15, 95% CI 0.72-1.73), early neonatal death (3.8% vs 2.1%, AOR 1.68, 95% CI 0.96-2.94), and NICU admission (26.6% vs 23.2%, AOR 0.93, 95% CI 0.62-1.39) were not., Conclusion: After a vaginal delivery of a vertex first twin, non-vertex presentation of the second twin is associated with increased odds of Apgar <7 at 5 minutes, but not of other maternal/perinatal outcomes. Presentation of the second twin is not as important a consideration in planning twin vaginal birth as previously considered.

Background: We report the main findings of the WHO Multicountry Survey on Maternal and Newborn Health (WHOMCS), which aimed to assess the burden of complications related to pregnancy, the coverage of key maternal health interventions, and use of the maternal severity index (MSI) in a global network of health facilities., Methods: In our cross-sectional study, we included women attending health facilities in Africa, Asia, Latin America, and the Middle East that dealt with at least 1000 childbirths per year and had the capacity to provide caesarean section. We obtained data from analysis of hospital records for all women giving birth and all women who had a severe maternal outcome (SMO; ie, maternal death or maternal near miss). We regarded coverage of key maternal health interventions as the proportion of the target population who received an indicated intervention (eg, the proportion of women with eclampsia who received magnesium sulphate). We used areas under the receiver operator characteristic curves (AUROC) with 95% CI to externally validate a previously reported MSI as an indicator of severity. We assessed the overall performance of care (ie, the ability to produce a positive effect on health outcomes) through standardised mortality ratios., Results: From May 1, 2010, to Dec 31, 2011, we included 314,623 women attending 357 health facilities in 29 countries (2538 had a maternal near miss and 486 maternal deaths occurred). The mean period of data collection in each health facility was 89 days (SD 21). 23,015 (7.3%) women had potentially life-threatening disorders and 3024 (1.0%) developed an SMO. 808 (26.7%) women with an SMO had post-partum haemorrhage and 784 (25.9%) had pre-eclampsia or eclampsia. Cardiovascular, respiratory, and coagulation dysfunctions were the most frequent organ dysfunctions in women who had an SMO. Reported mortality in countries with a high or very high maternal mortality ratio was two-to-three-times higher than that expected for the assessed severity despite a high coverage of essential interventions. The MSI had good accuracy for maternal death prediction in women with markers of organ dysfunction (AUROC 0.826 [95% CI 0.802-0.851])., Interpretation: High coverage of essential interventions did not imply reduced maternal mortality in the health-care facilities we studied. If substantial reductions in maternal mortality are to be achieved, universal coverage of life-saving interventions need to be matched with comprehensive emergency care and overall improvements in the quality of maternal health care. The MSI could be used to assess the performance of health facilities providing care to women with complications related to pregnancy., Funding: UNDP-UNFPA-UNICEF-WHO-World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP); WHO; USAID; Ministry of Health, Labour and Welfare of Japan; Gynuity Health Projects., (Copyright © 2013 World Health Organization. Published by Elsevier Ltd/Inc/BV. All rights reserved. Published by Elsevier Ltd. All rights reserved.)

Background: In 2001, the WHO Antenatal Care Trial (WHOACT) concluded that an antenatal care package of evidence-based screening, therapeutic interventions and education across four antenatal visits for low-risk women was not inferior to standard antenatal care and may reduce cost. However, an updated Cochrane review in 2010 identified an increased risk of perinatal mortality of borderline statistical significance in three cluster-randomized trials (including the WHOACT) in developing countries. We conducted a secondary analysis of the WHOACT data to determine the relationship between the reduced visits, goal-oriented antenatal care package and perinatal mortality., Methods: Exploratory analyses were conducted to assess the effect of baseline risk and timing of perinatal death. Women were stratified by baseline risk to assess differences between intervention and control groups. We used linear modeling and Poisson regression to determine the relative risk of fetal death, neonatal death and perinatal mortality by gestational age., Results: 12,568 women attended the 27 intervention clinics and 11,958 women attended the 26 control clinics. 6,160 women were high risk and 18,365 women were low risk. There were 161 fetal deaths (1.4%) in the intervention group compared to 119 fetal deaths in the control group (1.1%) with an increased overall adjusted relative risk of fetal death (Adjusted RR 1.27; 95% CI 1.03, 1.58). This was attributable to an increased relative risk of fetal death between 32 and 36 weeks of gestation (Adjusted RR 2.24; 95% CI 1.42, 3.53) which was statistically significant for high and low risk groups., Conclusion: It is plausible the increased risk of fetal death between 32 and 36 weeks gestation could be due to reduced number of visits, however heterogeneity in study populations or differences in quality of care and timing of visits could also be playing a role. Monitoring maternal, fetal and neonatal outcomes when implementing antenatal care protocols is essential. Implementing reduced visit antenatal care packages demands careful monitoring of maternal and perinatal outcomes, especially fetal death.

Context: For evidence-based practice to embed culturally in the workplace, teaching of evidence-based medicine (EBM) should be clinically integrated. In low-middle-income countries (LMICs) there is a scarcity of EBM-trained clinical tutors, lack of protected time for teaching EBM, and poor access to relevant databases in languages other than English., Objective: To evaluate the effects of a clinically integrated e-learning EBM course incorporating the World Health Organization (WHO) Reproductive Health Library (RHL) on knowledge, skills, and educational environment compared with traditional EBM teaching., Design, Setting, and Participants: International cluster randomized trial conducted between April 2009 and November 2010 among postgraduate trainees in obstetrics-gynecology in 7 LMICs (Argentina, Brazil, Democratic Republic of the Congo, India, Philippines, South Africa, Thailand). Each training unit was randomized to an experimental clinically integrated course consisting of e-modules using the RHL for learning activities and trainee assessments (31 clusters, 123 participants) or to a control self-directed EBM course incorporating the RHL (29 clusters, 81 participants). A facilitator with EBM teaching experience was available at all teaching units. Courses were administered for 8 weeks, with assessments at baseline and 4 weeks after course completion. The study was completed in 24 experimental clusters (98 participants) and 22 control clusters (68 participants)., Main Outcome Measures: Primary outcomes were change in EBM knowledge (score range, 0-62) and skills (score range, 0-14). Secondary outcome was educational environment (5-point Likert scale anchored between 1 [strongly agree] and 5 [strongly disagree])., Results: At baseline, the study groups were similar in age, year of training, and EBM-related attitudes and knowledge. After the trial, the experimental group had higher mean scores in knowledge (38.1 [95% CI, 36.7 to 39.4] in the control group vs 43.1 [95% CI, 42.0 to 44.1] in the experimental group; adjusted difference, 4.9 [95% CI, 2.9 to 6.8]; P < .001) and skills (8.3 [95% CI, 7.9 to 8.7] vs 9.1 [95% CI, 8.7 to 9.4]; adjusted difference, 0.7 [95% CI, 0.1 to 1.3]; P = .02). Although there was no difference in improvement for the overall score for educational environment (6.0 [95% CI, -0.1 to 12.0] vs 13.6 [95% CI, 8.0 to 19.2]; adjusted difference, 9.6 [95% CI, -6.8 to 26.1]; P = .25), there was an associated mean improvement in the domains of general relationships and support (-0.5 [95% CI, -1.5 to 0.4] vs 0.3 [95% CI, -0.6 to 1.1]; adjusted difference, 2.3 [95% CI, 0.2 to 4.3]; P = .03) and EBM application opportunities (0.5 [95% CI, -0.7 to 1.8] vs 2.9 [95%, CI, 1.8 to 4.1]; adjusted difference, 3.3 [95% CI, 0.1 to 6.5]; P = .04)., Conclusion: In a group of LMICs, a clinically integrated e-learning EBM curriculum in reproductive health compared with a self-directed EBM course resulted in higher knowledge and skill scores and improved educational environment., Trial Registration: anzctr.org.au Identifier: ACTRN12609000198224.

Background: Supplementary feeding is defined as the provision of extra food to children or families beyond the normal ration of their home diets. The impact of food supplementation on child growth merits careful evaluation in view of the reliance of many states and non-governmental organisations on this intervention to improve child health in low and middle income countries (LMIC). This is an update of a Cochrane review first published in 2005., Objectives: To evaluate the effectiveness of community-based supplementary feeding for promoting the physical growth of children under five years of age in LMIC., Search Methods: For this updated review  we searched the following databases on 31 January 2011: CENTRAL (The Cochrane Library), MEDLINE (1948 to January week 3, 2011), EMBASE (1980 to week 3, 2011), CINAHL (1937 to 27 January 2011), LILACS (all years), WorldCat for dissertations and theses (all years) and ClinicalTrials.gov (all years)., Selection Criteria: Randomised controlled trials (RCTs) evaluating supplementary feeding in comparison to a control group (no intervention or a placebo such as food with a very low number of nutrients and calories) in children from birth to five years of age in LMIC., Data Collection and Analysis: Two review authors independently extracted and analysed the data., Main Results: We included eight RCTs (n = 1243 children) that were at relatively high risk of bias. We found high levels of clinical heterogeneity in the participants, interventions and outcome measures across studies. Nevertheless, in order to quantify pooled effects of supplementary feeding, we decided to combine studies according to prespecified characteristics. These were the children's age (younger or older than 24 months), their nutritional status at baseline (stunted or wasted, or not stunted or wasted) and the duration of the intervention (less or more than 12 months). A statistically significant difference of effect was only found for length during the intervention in children aged less than 12 months (two studies; 795 children; mean difference 0.19 cm; 95% confidence interval (CI) 0.07 to 0.31). Based on the summary statistic calculated for each study, the mean difference (MD) between intervention and control groups ranged from 0.48 cm (95% CI 0.07 to 0.89) to 1.3 cm (95% CI 0.03 to 2.57) after 3 and 12 months of intervention, respectively. Data on potential adverse effects were lacking., Authors' Conclusions: The scarcity of available studies and their heterogeneity makes it difficult to reach any firm conclusions. The review findings suggest supplementary feeding has a negligible impact on child growth; however, the pooled results should be interpreted with great caution because the studies included in the review are clinically diverse. Future studies should address issues of research design, including sample size calculation, to detect meaningful clinical effects and adequate intervention allocation concealment. In the meantime, families and children in need should be provided appropriate feeding, health care and sanitation without waiting for new RCTs to establish a research basis for feeding children.

Background: Active management of the third stage of labour reduces the risk of post-partum haemorrhage. We aimed to assess whether controlled cord traction can be omitted from active management of this stage without increasing the risk of severe haemorrhage., Methods: We did a multicentre, non-inferiority, randomised controlled trial in 16 hospitals and two primary health-care centres in Argentina, Egypt, India, Kenya, the Philippines, South Africa, Thailand, and Uganda. Women expecting to deliver singleton babies vaginally (ie, not planned caesarean section) were randomly assigned (in a 1:1 ratio) with a centrally generated allocation sequence, stratified by country, to placental delivery with gravity and maternal effort (simplified package) or controlled cord traction applied immediately after uterine contraction and cord clamping (full package). After randomisation, allocation could not be concealed from investigators, participants, or assessors. Oxytocin 10 IU was administered immediately after birth with cord clamping after 1-3 min. Uterine massage was done after placental delivery according to local policy. The primary (non-inferiority) outcome was blood loss of 1000 mL or more (severe haemorrhage). The non-inferiority margin for the risk ratio was 1·3. Analysis was by modified intention-to-treat, excluding women who had emergency caesarean sections. This trial is registered with the Australian and New Zealand Clinical Trials Registry, ACTRN 12608000434392., Findings: Between June 1, 2009, and Oct 30, 2010, 12,227 women were randomly assigned to the simplified package group and 12,163 to the full package group. After exclusion of women who had emergency caesarean sections, 11,861 were in the simplified package group and 11,820 were in the full package group. The primary outcome of blood loss of 1000 mL or more had a risk ratio of 1·09 (95% CI 0·91-1·31) and the upper 95% CI limit crossed the pre-stated non-inferiority margin. One case of uterine inversion occurred in the full package group. Other adverse events were haemorrhage-related., Interpretation: Although the hypothesis of non-inferiority was not met, omission of controlled cord traction has very little effect on the risk of severe haemorrhage. Scaling up of haemorrhage prevention programmes for non-hospital settings can safely focus on use of oxytocin., Funding: United States Agency for International Development and UN Development Programme/UN Population Fund/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction, Department of Reproductive Health and Research., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: Postpartum haemorrhage is among the biggest contributor to maternal mortality worldwide. Prevention of this condition includes routine use of uterotonic in the third stage of labour, which has been recommended throughout the world. Use of umbilical route to deliver this uterotonic after delivery of the baby has been proposed. Therapeutic use of this has been assessed, although routine (prophylactic) use of this has not been evaluated., Objectives: To compare, from the best available evidence, the effects of umbilical vein injection of a saline solution alone or with any uterotonic drug versus an alternative solution with or without any other uterotonic agent or expectant management or any other method for routine management of the third stage of labour, on maternal and perinatal outcomes., Search Methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 January 2012) and reference lists of retrieved studies., Selection Criteria: We included all randomised controlled trials comparing the effects of umbilical vein injection of a saline solution alone or with any uterotonic drug versus any other alternative methods., Data Collection and Analysis: Two review authors independently assessed the eligibility and trial quality. Two review authors extracted data. Data were checked for accuracy., Main Results: We included nine studies involving 1118 women.We identified four comparisons. One comparison included six studies (which randomised 394 women) comparing umbilical vein injection of normal saline plus oxytocin versus that of normal saline, as well as three other comparisons, each of which includes one study. Comparing intraumbilical injection of normal saline plus oxytocin with intraumbilical injection of saline only, there was no evidence of difference in any of the relevant outcomes reported namely the number of women who required blood transfusion, the incidence of manual removal of placenta, blood loss, and length of the third stage of labour. Subgroup analyses by both total amount of solution administered and dose of oxytocin showed no evidence of difference. Other comparisons included only one study for each, and there was no relevant information available., Authors' Conclusions: Routine use of oxytocin or any other uterotonics with normal saline via umbilical vein injection is not recommended until new evidence is available. Further research should be conducted to show effectiveness of oxytocin with normal saline via umbilical vein injection.

Background: Effective interventions to reduce mortality and morbidity in maternal and newborn health already exist. Information about quality and performance of care and the use of critical interventions are useful for shaping improvements in health care and strengthening the contribution of health systems towards the Millennium Development Goals 4 and 5. The near-miss concept and the criterion-based clinical audit are proposed as useful approaches for obtaining such information in maternal and newborn health care. This paper presents the methods of the World Health Organization Multicountry Study in Maternal and Newborn Health. The main objectives of this study are to determine the prevalence of maternal near-miss cases in a worldwide network of health facilities, evaluate the quality of care using the maternal near-miss concept and the criterion-based clinical audit, and develop the near-miss concept in neonatal health., Methods/design: This is a large cross-sectional study being implemented in a worldwide network of health facilities. A total of 370 health facilities from 29 countries will take part in this study and produce nearly 275,000 observations. All women giving birth, all maternal near-miss cases regardless of the gestational age and delivery status and all maternal deaths during the study period comprise the study population. In each health facility, medical records of all eligible women will be reviewed during a data collection period that ranges from two to three months according to the annual number of deliveries., Discussion: Implementing the systematic identification of near-miss cases, mapping the use of critical evidence-based interventions and analysing the corresponding indicators are just the initial steps for using the maternal near-miss concept as a tool to improve maternal and newborn health. The findings of projects using approaches similar to those described in this manuscript will be a good starter for a more comprehensive dialogue with governments, professionals and civil societies, health systems or facilities for promoting best practices, improving quality of care and achieving better health for mothers and children.

Objective: To assess the frequency of elective induction of labour and its determinants in selected Latin America countries; quantify success in attaining vaginal delivery, and compare rates of caesarean and adverse maternal and perinatal outcomes after elective induction versus spontaneous labour in low-risk pregnancies., Methods: Of 37,444 deliveries in women with low-risk pregnancies, 1847 (4.9%) were electively induced. The factors associated with adverse maternal and perinatal outcomes among cases of spontaneous and induced onset of labour were compared. Odds ratios for factors potentially associated with adverse outcomes were calculated, as were the relative risks of having an adverse maternal or perinatal outcome (both with their 95% confidence intervals). Adjustment using multiple logistic regression models followed these analyses., Findings: Of 11,077 cases of induced labour, 1847 (16.7%) were elective. Elective inductions occurred in 4.9% of women with low-risk pregnancies (37,444). Oxytocin was the most common method used (83% of cases), either alone or combined with another. Of induced deliveries, 88.2% were vaginal. The most common maternal adverse events were: (i) a higher postpartum need for uterotonic drugs, (ii) a nearly threefold risk of admission to the intensive care unit; (iii) a fivefold risk of postpartum hysterectomy, and (iv) an increased need for anaesthesia/analgesia. Perinatal outcomes were satisfactory except for a 22% higher risk of delayed breastfeeding (i.e. initiation between 1 hour and 7 days postpartum)., Conclusion: Caution is mandatory when indicating elective labour induction because the increased risk of maternal and perinatal adverse outcomes is not outweighed by clear benefits.

Background: If a retained placenta is left untreated, there is a high risk of maternal death. However, manual removal of the placenta is an invasive procedure with serious complications of haemorrhage, infection or genital tract trauma., Objectives: To assess the use of umbilical vein injection (UVI) of saline solution alone or with oxytocin in comparison either with expectant management or with an alternative solution or other uterotonic agent for retained placenta., Search Strategy: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (28 February 2011)., Selection Criteria: Randomized trials comparing UVI of saline or other fluids, with or without oxytocics, either with expectant management or with an alternative solution or other uterotonic agent, in the management of retained placenta., Data Collection and Analysis: Two review authors assessed the methodological quality of the studies and extracted the data., Main Results: We included 15 trials (1704 women). The trials were of variable quality. Compared with expectant management, UVI of saline solution alone did not show any significant difference in the incidence of manual removal of the placenta (risk ratio (RR) 0.99; 95% confidence interval (CI) 0.84 to 1.16). UVI of oxytocin solution compared with expectant management showed no reduction in the need for manual removal (RR 0.87; 95% CI 0.74 to 1.03).Oxytocin solution compared with saline solution alone showed a reduction in manual removal of the placenta, but this was not statistically significant (RR 0.91; 95% CI 0.82 to 1.00). When only high-quality studies were assessed, there was no statistical difference (RR 0.92; 95% CI 0.83 to 1.01). We detected no differences in any of the other outcomes.UVI of oxytocin solution compared with UVI of plasma expander showed no statistically significant difference in the outcomes assessed by the only one small trial included. Prostaglandin solution compared with saline solution alone was associated with a statistically significant lower incidence in manual removal of placenta (RR 0.42; 95% CI 0.22 to 0.82) but we observed no difference in the other outcomes evaluated. Prostaglandin plus saline solution showed a statistically significant reduction in manual removal of placenta when compared with oxytocin plus saline solution (RR 0.43; 95% CI 0.25 to 0.75), and we also observed a small reduction in time from injection to placental delivery (mean difference -6.00; 95% CI -8.78 to -3.22). However, there were only two small trials contributing to this meta-analysis., Authors' Conclusions: UVI of oxytocin solution is an inexpensive and simple intervention that could be performed while placental delivery is awaited. However, high-quality randomized trials show that the use of oxytocin has little or no effect. Further research into the optimal timing of manual removal and into UVI of prostaglandins or plasma expander is warranted.

Background: The number of visits for antenatal (prenatal) care developed without evidence of how many visits are necessary. The content of each visit also needs evaluation., Objectives: To compare the effects of antenatal care programmes with reduced visits for low-risk women with standard care., Search Strategy: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (April 2010), reference lists of articles and contacted researchers in the field., Selection Criteria: Randomised trials comparing a reduced number of antenatal visits, with or without goal-oriented care, with standard care., Data Collection and Analysis: Two authors assessed trial quality and extracted data independently., Main Results: We included seven trials (more than 60,000 women): four in high-income countries with individual randomisation; three in low- and middle-income countries with cluster randomisation (clinics as the unit of randomisation). The number of visits for standard care varied, with fewer visits in low- and middle- income country trials. In studies in high-income countries, women in the reduced visits groups, on average, attended between 8.2 and 12 times. In low- and middle- income country trials, many women in the reduced visits group attended on fewer than five occasions, although in these trials the content as well as the number of visits was changed, so as to be more 'goal oriented'.Perinatal mortality was increased for those randomised to reduced visits rather than standard care, and this difference was borderline for statistical significance (five trials; risk ratio (RR) 1.14; 95% confidence interval (CI) 1.00 to 1.31). In the subgroup analysis, for high-income countries the number of deaths was small (32/5108), and there was no clear difference between the groups (2 trials; RR 0.90; 95% CI 0.45 to 1.80); for low- and middle-income countries perinatal mortality was significantly higher in the reduced visits group (3 trials RR 1.15; 95% CI 1.01 to 1.32). Reduced visits were associated with a reduction in admission to neonatal intensive care that was borderline for significance (RR 0.89; 95% CI 0.79 to 1.02). There were no clear differences between the groups for the other reported clinical outcomes.Women in all settings were less satisfied with the reduced visits schedule and perceived the gap between visits as too long. Reduced visits may be associated with lower costs., Authors' Conclusions: In settings with limited resources where the number of visits is already low, reduced visits programmes of antenatal care are associated with an increase in perinatal mortality compared to standard care, although admission to neonatal intensive care may be reduced. Women prefer the standard visits schedule. Where the standard number of visits is low, visits should not be reduced without close monitoring of fetal and neonatal outcome.

Background: Delayed umbilical cord clamping could increase iron stores and prevent iron deficiency in infants. To test this hypothesis we measured serum ferritin and hemoglobin levels at six months of age in term infants who had participated in a randomized controlled trial, assessing the effect of cord clamping timing on neonatal hematocrit values and clinical outcome. Main outcome measure. Serum ferritin level at six months of age., Methods: Out of the 276 mothers and their infants that participated in the initial study, 255 (92.4%) were followed up to six months and included in this study. Of these, 86 had their cords clamped within the first 15 seconds (early clamping), 83 at one minute, and 83 at three minutes. The pediatricians in charge of the evaluations during the follow-up period and personnel in charge of the biochemical tests were blinded to the assignment group. In all but 3 infants the ferritin levels and hemoglobin levels were measured at six months of age., Results: Mothers and infants in the three groups had similar baseline characteristics. Serum ferritin levels were significantly higher in the infants of the three minutes group than in the infants of the early group: 33.2 microg/L vs. 20.9 microg/L (geometric mean ratio: 1.6; 95% CI: 1.2 to 2.11) but no difference was observed in one minute group (25.5 microg/L) vs. early group. There were no significant differences in mean hemoglobin values, 10.6 g/dl (SD 1,1); 10.8 g/dl (SD 0.9) and 10.7 g/dl (SD 1.0) between groups early, one minute, and three minutes, respectively. Although there were no significant differences between groups, the prevalence of iron deficiency anemia (hemoglobin < 10.5 g/dl and ferritin < 9 microg/L) was 3 times more frequent in early clampling group (7.2%) than in three minutes group (2.4%) (RR: 0.30; IC 95%: 0.10-1.60)., Conclusions: Delayed umbilical cord clamping at three minutes significantly increases serum ferritin levels in infants at 6 months of age. No significant differences were found between groups in mean hemoglobin levels.

Background: Post-partum haemorrhage is a leading cause of global maternal morbidity and mortality. Misoprostol, a prostaglandin analogue with uterotonic activity, is an attractive option for treatment because it is stable, active orally, and inexpensive. We aimed to assess the effectiveness of misoprostol as an adjunct to standard uterotonics compared with standard uterotonics alone for treatment of post-partum haemorrhage., Methods: Women delivering vaginally who had clinically diagnosed post-partum haemorrhage due to uterine atony were enrolled from participating hospitals in Argentina, Egypt, South Africa, Thailand, and Vietnam between July, 2005, and August, 2008. Computer-generated randomisation was used to assign women to receive 600 microg misoprostol or matching placebo sublingually; both groups were also given routine injectable uterotonics. Allocation was concealed by distribution of sealed and sequentially numbered treatment packs in the order that women were enrolled. Providers and women were masked to treatment assignment. The primary outcome was blood loss of 500 mL or more within 60 min after randomisation. Analysis was by intention to treat. This study is registered, number ISRCTN34455240., Findings: 1422 women were assigned to receive misoprostol (n=705) or placebo (n=717). The proportion of women with blood loss of 500 mL or more within 60 min was similar between the misoprostol group (100 [14%]) and the placebo group (100 [14%]; relative risk 1.02, 95% CI 0.79-1.32). In the first 60 min, an increased proportion of women on misoprostol versus placebo, had shivering (455/704 [65%] vs 230/717 [32%]; 2.01, 1.79-2.27) and body temperature of 38 degrees C or higher (303/704 [43%] vs 107/717 [15%]; 2.88, 2.37-2.50)., Interpretation: Findings from this study do not support clinical use of 600 microg sublingual misoprostol in addition to standard injectable uterotonics for treatment of post-partum haemorrhage., Funding: Bill & Melinda Gates Foundation, and UNDP/UNFPA/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Background and Objectives: Evidence-based health care requires clinicians to engage with use of evidence in decision-making at the workplace. A learner-centred, problem-based course that integrates e-learning in the clinical setting has been developed for application in obstetrics and gynaecology units. The course content uses the WHO reproductive health library (RHL) as the resource for systematic reviews. This project aims to evaluate a clinically integrated teaching programme for incorporation of evidence provided through the WHO RHL. The hypothesis is that the RHL-EBM (clinically integrated e-learning) course will improve participants' knowledge, skills and attitudes, as well as institutional practice and educational environment, as compared to the use of standard postgraduate educational resources for EBM teaching that are not clinically integrated., Methods: The study will be a multicentre, cluster randomized controlled trial, carried out in seven countries (Argentina, Brazil, Democratic Republic of Congo, India, Philippines, South Africa, Thailand), involving 50-60 obstetrics and gynaecology teaching units. The trial will be carried out on postgraduate trainees in the first two years of their training. In the intervention group, trainees will receive the RHL-EBM course. The course consists of five modules, each comprising self-directed e-learning components and clinically related activities, assignments and assessments, coordinated between the facilitator and the postgraduate trainee. The course will take about 12 weeks, with assessments taking place pre-course and 4 weeks post-course. In the control group, trainees will receive electronic, self-directed EBM-teaching materials. All data collection will be online.The primary outcome measures are gain in EBM knowledge, change in attitudes towards EBM and competencies in EBM measured by multiple choice questions (MCQs) and a skills-assessing questionniare administered eletronically. These questions have been developed by using questions from validated questionnaires and adapting them to the current course. Secondary outcome measure will be educational environment towards EBM which will be assessed by a specifically developed questionnaire., Expected Outcomes: The trial will determine whether the RHL EBM (clinically integrated e-leraning) course will increase knowledge, skills and attitudes towards EBM and improve the educational environment as compared to standard teaching that is not clinically integrated. If effective, the RHL-EBM course can be implemented in teaching institutions worldwide in both, low-and middle income countries as well as industrialized settings. The results will have a broader impact than just EBM training because if the approach is successful then the same educational strategy can be used to target other priority clinical and methodological areas., Trial Registration: ACTRN12609000198224.

Background: There has been concern about rising rates of caesarean section worldwide. This Article reports the third phase of the WHO global survey, which aimed to estimate the rate of different methods of delivery and to examine the relation between method of delivery and maternal and perinatal outcomes in selected facilities in Africa and Latin America in 2004-05, and in Asia in 2007-08., Methods: Nine countries participated in the Asia global survey: Cambodia, China, India, Japan, Nepal, Philippines, Sri Lanka, Thailand, and Vietnam. In each country, the capital city and two other regions or provinces were randomly selected. We studied all women admitted for delivery during 3 months in institutions with 6000 or fewer expected deliveries per year and during 2 months in those with more than 6000 deliveries. We gathered data for institutions to obtain a detailed description of the health facility and its resources for obstetric care. We obtained data from women's medical records to summarise obstetric and perinatal events., Findings: We obtained data for 109 101 of 112 152 deliveries reported in 122 recruited facilities (97% coverage), and analysed 107 950 deliveries. The overall rate of caesarean section was 27.3% (n=29 428) and of operative vaginal delivery was 3.2% (n=3465). Risk of maternal mortality and morbidity index (at least one of: maternal mortality, admission to intensive care unit [ICU], blood transfusion, hysterectomy, or internal iliac artery ligation) was increased for operative vaginal delivery (adjusted odds ratio 2.1, 95% CI 1.7-2.6) and all types of caesarean section (antepartum without indication 2.7, 1.4-5.5; antepartum with indication 10.6, 9.3-12.0; intrapartum without indication 14.2, 9.8-20.7; intrapartum with indication 14.5, 13.2-16.0). For breech presentation, caesarean section, either antepartum (0.2, 0.1-0.3) or intrapartum (0.3, 0.2-0.4), was associated with improved perinatal outcomes, but also with increased risk of stay in neonatal ICU (2.0, 1.1-3.6; and 2.1, 1.2-3.7, respectively)., Interpretation: To improve maternal and perinatal outcomes, caesarean section should be done only when there is a medical indication., Funding: US Agency for International Development (USAID); UNDP/UNFPA/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), WHO, Switzerland; Ministry of Health, Labour and Welfare of Japan; Ministry of Public Health, China; and Indian Council of Medical Research., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Objective: To develop an indicator of maternal near miss as a proxy for maternal death and to study its association with maternal factors and perinatal outcomes., Methods: In a multicenter cross-sectional study, we collected maternal and perinatal data from the hospital records of a sample of women admitted for delivery over a period of two to three months in 120 hospitals located in eight Latin American countries. We followed a stratified multistage cluster random design. We assessed the intra-hospital occurrence of severe maternal morbidity and the latter's association with maternal characteristics and perinatal outcomes., Findings: Of the 97,095 women studied, 2964 (34 per 1000) were at higher risk of dying in association with one or more of the following: being admitted to the intensive care unit (ICU), undergoing a hysterectomy, receiving a blood transfusion, suffering a cardiac or renal complication, or having eclampsia. Being older than 35 years, not having a partner, being a primipara or para > 3, and having had a Caesarean section in the previous pregnancy were factors independently associated with the occurrence of severe maternal morbidity. They were also positively associated with an increased occurrence of low and very low birth weight, stillbirth, early neonatal death, admission to the neonatal ICU, a prolonged maternal postpartum hospital stay and Caesarean section., Conclusion: Women who survive the serious conditions described could be pragmatically considered cases of maternal near miss. Interventions to reduce maternal and perinatal mortality should target women in these high-risk categories.

Background: Retained placenta is associated with post-partum haemorrhage. Meta-analysis has suggested that umbilical injection of oxytocin could increase placental expulsion without the need for a surgeon or anaesthetic. We assessed the effect of high-dose umbilical vein oxytocin as a treatment for retained placenta., Methods: In this double-blind, placebo-controlled trial, haemodynamically stable women with a retained placenta for more than 30 min were recruited from 13 sites in the UK, Uganda, and Pakistan. 577 women were randomly assigned by a computer-generated randomisation list stratified by centre to 30 mL saline containing either 50 IU oxytocin (n=292) or 5 mL water (n=285), which was injected into the placenta through an umbilical vein catheter. All trial participants, study workers, and data handlers were masked to individual allocations. The primary outcome was the need for manual removal of the placenta. Analysis was by intention to treat. This study is registered, number ISRCTN 13204258., Findings: The primary outcome was recorded for all participants. We detected no difference between the groups in the need for manual removal of placenta (oxytocin 179/292 [61.3%] vs placebo 177/285 [62.1%]; relative risk 0.98, 95% CI 0.87-1.12; p=0.84). The need for manual removal was higher in the UK (overall 250/361 [69%]) than in Uganda (90/190 [47%]) or Pakistan (16/26 [62%]). Adverse events did not differ between the two groups., Interpretation: Umbilical oxytocin has no clinically significant effect on the need for manual removal for women with retained placenta., Funding: WHO, WellBeing of Women, Pakistan Higher Education Commission., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Calcium supplementation in mothers with low calcium intake has been of interest recently because of its association with optimal fetal growth and improved pre-eclampsia-related outcomes. While the effects of calcium supplementation have demonstrated benefits in prolonging gestation and subsequently improving birthweight, no specific studies have identified the longitudinal effects of supplementation on fetal growth in utero. Data were analysed in the context of the World Health Organization trial of calcium supplementation in calcium-deficient women. Five hundred and ten healthy, primiparous pregnant Argentinean women were randomised (at <20 weeks gestation) to either placebo (n = 230) or calcium supplements (1500 mg calcium/day in 3 divided doses; n = 231). Growth parameters in utero were assessed with serial ultrasound scans. Birthweight, length, head, abdominal and thigh circumferences were recorded at delivery. No differences were found in fetal biometric measurements recorded at 20, 24, 28, 32 and 36 weeks gestation between fetuses of women who were supplemented with calcium and those who were not. Similarly, neonatal characteristics and anthropometric measurements recorded at delivery were comparable in both groups. We conclude that calcium supplementation of 1500 mg calcium/day in pregnant women with low calcium intake does not appear to impact on fetal somatic or skeletal growth.