Women's caesarean section preferences: A multicountry cross-sectional survey in low- and middle-income countries.

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 (ß=+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.

Third stage of labor: evidence-based practice for prevention of adverse maternal and neonatal outcomes.

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.

How does hospital organisation influence the use of caesarean sections in low- and middle-income countries? A cross-sectional survey in Argentina, Burkina Faso, Thailand and Vietnam for the QUALI-DEC project.

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.

Multicountry research on comprehensive abortion policy implementation in Latin America: a mixed-methods study protocol.

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.

Implementing the QUALI-DEC project in Argentina, Burkina Faso, Thailand and Viet Nam: a process delineation and theory-driven process evaluation protocol.

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.

Factors affecting the implementation of calcium supplementation strategies during pregnancy to prevent pre-eclampsia: a mixed-methods systematic review.

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.

Calcium supplementation to prevent pre-eclampsia: protocol for an individual participant data meta-analysis, network meta-analysis and health economic evaluation.

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 tau2, I2 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.

Severe Adverse Maternal and Neonatal Outcomes in Adolescent Mother-Newborn Dyads: A Multicentre Study in Latin America.

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.

Caesarean section or vaginal delivery for low-risk pregnancy? Helping women make an informed choice in low- and middle-income countries.

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.

Duration of third stage labour and postpartum blood loss: a secondary analysis of the WHO CHAMPION trial data.

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.

The duration of the third stage of labour (TSL) seems to be an important risk factor for greater postpartum blood loss, as literature shows that a longer TSL can be associated with more blood loss. Active management of third stage of labour (AMTSL), included in the WHO guidelines for prevention of postpartum haemorrhage (PPH), is effective in reducing both the amount of postpartum blood loss and the duration of the third stage. To better describe the association between duration of TSL and postpartum blood loss in women receiving AMTSL, we conducted this secondary analysis of WHO CHAMPION trial data.To assess the association between the duration of third stage of labour and postpartum blood loss, a subcohort of the CHAMPION modified ITT population was selected by excluding women with missing blood loss or missing TSL duration or TSL duration more than 60 min and women with interventions. Thus, the subcohort consisted of 10,040 women.In women with vaginal birth and not receiving interventions for treating atonic PPH or other sources of bleeding, and with TSL duration up to 60 min, there was a positive association between duration of the TSL and postpartum blood loss. The blood loss rose steeply with duration in women with TSL of 10 min or less, while in women with longer TSL duration the slope was less steep.There was no evidence of a difference between oxytocin and HS carbetocin in the pattern of association of duration of the TSL and blood loss.

Abortion-related morbidity in six Latin American and Caribbean countries: findings of the WHO/HRP multi-country survey on abortion (MCS-A).

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.

Correction: The World Health Organization Fetal Growth Charts: A Multinational Longitudinal Study of Ultrasound Biometric Measurements and Estimated Fetal Weight.

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

Implementation and evaluation of nonclinical interventions for appropriate use of cesarean section in low- and middle-income countries: protocol for a multisite hybrid effectiveness-implementation type III trial.

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.

High fever after sublingual administration of misoprostol for treatment of post-partum haemorrhage: a hospital-based, prospective observational study in Argentina.

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.

OBJECTIF: Caractériser la survenue de fièvre (≥ 38,0°C) après traitement d'une hémorragie post-partum (HPP) avec du misoprostol sublingual à 800 mcg en Amérique latine, où des taux élevés d'effets thermorégulateurs du misoprostol et une sensibilité accrue des receveurs à une forte fièvre ont été documentés. MÉTHODES: Une étude observationnelle prospective dans des hôpitaux en Argentine a recruté des femmes consentantes atteintes d'HPP atonique après un accouchement vaginal éligibles pour recevoir du misoprostol. La température corporelle a été évaluée 30, 60, 90 et 120 minutes après le traitement; d'autres effets ont été enregistrés. L'incidence d'une fièvre élevée ≥40,0°C (critère principal) a été comparée au taux observé précédemment en Equateur. Des régressions logistiques ont été effectuées pour identifier les prédicteurs cliniques et ceux basés sur la population de la fièvre induite par le misoprostol . RÉSULTATS: Des frissons transitoires et de la fièvre ont été ressentis par 75% (37/49) des participantes traitées et décrits comme acceptables par les trois quarts des femmes interrogées (35/47). Le taux de fièvre élevé était de 12% (6/49), [intervalle de confiance (IC) à 95%: 4,6, 24,8] contre 35,6% en Equateur après traitement au misoprostol (58/163) [IC95%: 28,3, 43,5], p = 0,002). Les prédicteurs significatifs de la fièvre induite par le misoprostol (selon le modèle) étaient: hémoglobine avant l'accouchement <11,0 g/dL, expulsion placentaire rapide et âge plus élevé de la femme. Aucun résultat sévère n'a été signalé avant le sortie d'hôpital. CONCLUSIONS: Le misoprostol pour traiter l'HPP en Argentine a entraîné un taux de fièvre élevée significativement plus bas qu'en Equateur, bien que les taux dans les deux pays soient notablement plus élevés que les taux observés ailleurs. Une meilleure compréhension des effets secondaires du misoprostol et des facteurs impliqués dans leur apparition, y compris la génétique, aidera à atténuer les inquiétudes. L'apparition de frissons peut être le moyen le plus simple de savoir si l'on peut également s'attendre à de la fièvre.

Does route matter? Impact of route of oxytocin administration on postpartum bleeding: A double-blind, randomized controlled trial.

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.

Methods for blood loss estimation after vaginal birth.

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.

Effect of high dose folic acid supplementation in pregnancy on pre-eclampsia (FACT): double blind, phase III, randomised controlled, international, multicentre trial.

OBJECTIVE: To determine the efficacy of high dose folic acid supplementation for prevention of pre-eclampsia in women with at least one risk factor: pre-existing hypertension, prepregnancy diabetes (type 1 or 2), twin pregnancy, pre-eclampsia in a previous pregnancy, or body mass index ≥35. DESIGN: Randomised, phase III, double blinded international, multicentre clinical trial. SETTING: 70 obstetrical centres in five countries (Argentina, Australia, Canada, Jamaica, and UK). PARTICIPANTS: 2464 pregnant women with at least one high risk factor for pre-eclampsia were randomised between 2011 and 2015 (1144 to the folic acid group and 1157 to the placebo group); 2301 were included in the intention to treat analyses. INTERVENTION: Eligible women were randomised to receive either daily high dose folic acid (four 1.0 mg oral tablets) or placebo from eight weeks of gestation to the end of week 16 of gestation until delivery. Clinicians, participants, adjudicators, and study staff were masked to study treatment allocation. MAIN OUTCOME MEASURE: The primary outcome was pre-eclampsia, defined as hypertension presenting after 20 weeks' gestation with major proteinuria or HELLP syndrome (haemolysis, elevated liver enzymes, low platelets). RESULTS: Pre-eclampsia occurred in 169/1144 (14.8%) women in the folic acid group and 156/1157 (13.5%) in the placebo group (relative risk 1.10, 95% confidence interval 0.90 to 1.34; P=0.37). There was no evidence of differences between the groups for any other adverse maternal or neonatal outcomes. CONCLUSION: Supplementation with 4.0 mg/day folic acid beyond the first trimester does not prevent pre-eclampsia in women at high risk for this condition. TRIAL REGISTRATION: Current Controlled Trials ISRCTN23781770 and ClinicalTrials.gov NCT01355159.

Heat-Stable Carbetocin versus Oxytocin to Prevent Hemorrhage after Vaginal Birth.

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 .).

Correction: The World Health Organization Fetal Growth Charts: A Multinational Longitudinal Study of Ultrasound Biometric Measurements and Estimated Fetal Weight.

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