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 .).

How women are treated during facility-based childbirth in four countries: a cross-sectional study with labour observations and community-based surveys.

BACKGROUND: Women across the world are mistreated during childbirth. We aimed to develop and implement evidence-informed, validated tools to measure mistreatment during childbirth, and report results from a cross-sectional study in four low-income and middle-income countries. METHODS: We prospectively recruited women aged at least 15 years in twelve health facilities (three per country) in Ghana, Guinea, Myanmar, and Nigeria between Sept 19, 2016, and Jan 18, 2018. Continuous observations of labour and childbirth were done from admission up to 2 h post partum. Surveys were administered by interviewers in the community to women up to 8 weeks post partum. Labour observations were not done in Myanmar. Data were collected on sociodemographics, obstetric history, and experiences of mistreatment. FINDINGS: 2016 labour observations and 2672 surveys were done. 838 (41·6%) of 2016 observed women and 945 (35·4%) of 2672 surveyed women experienced physical or verbal abuse, or stigma or discrimination. Physical and verbal abuse peaked 30 min before birth until 15 min after birth (observation). Many women did not consent for episiotomy (observation: 190 [75·1%] of 253; survey: 295 [56·1%] of 526) or caesarean section (observation: 35 [13·4%] of 261; survey: 52 [10·8%] of 483), despite receiving these procedures. 133 (5·0%) of 2672 women or their babies were detained in the facility because they were unable to pay the bill (survey). Younger age (15-19 years) and lack of education were the primary determinants of mistreatment (survey). For example, younger women with no education (odds ratio [OR] 3·6, 95% CI 1·6-8·0) and younger women with some education (OR 1·6, 1·1-2·3) were more likely to experience verbal abuse, compared with older women (≥30 years), adjusting for marital status and parity. INTERPRETATION: More than a third of women experienced mistreatment and were particularly vulnerable around the time of birth. Women who were younger and less educated were most at risk, suggesting inequalities in how women are treated during childbirth. Understanding drivers and structural dimensions of mistreatment, including gender and social inequalities, is essential to ensure that interventions adequately account for the broader context. FUNDING: United States Agency for International Development and the UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction, Department of Reproductive Health and Research, WHO.

Progression of the first stage of spontaneous labour: A prospective cohort study in two sub-Saharan African countries.

BACKGROUND: Escalation in the global rates of labour interventions, particularly cesarean section and oxytocin augmentation, has renewed interest in a better understanding of natural labour progression. Methodological advancements in statistical and computational techniques addressing the limitations of pioneer studies have led to novel findings and triggered a re-evaluation of current labour practices. As part of the World Health Organization's Better Outcomes in Labour Difficulty (BOLD) project, which aimed to develop a new labour monitoring-to-action tool, we examined the patterns of labour progression as depicted by cervical dilatation over time in a cohort of women in Nigeria and Uganda who gave birth vaginally following a spontaneous labour onset. METHODS AND FINDINGS: This was a prospective, multicentre, cohort study of 5,606 women with singleton, vertex, term gestation who presented at ≤ 6 cm of cervical dilatation following a spontaneous labour onset that resulted in a vaginal birth with no adverse birth outcomes in 13 hospitals across Nigeria and Uganda. We independently applied survival analysis and multistate Markov models to estimate the duration of labour centimetre by centimetre until 10 cm and the cumulative duration of labour from the cervical dilatation at admission through 10 cm. Multistate Markov and nonlinear mixed models were separately used to construct average labour curves. All analyses were conducted according to three parity groups: parity = 0 (n = 2,166), parity = 1 (n = 1,488), and parity = 2+ (n = 1,952). We performed sensitivity analyses to assess the impact of oxytocin augmentation on labour progression by re-examining the progression patterns after excluding women with augmented labours. Labour was augmented with oxytocin in 40% of nulliparous and 28% of multiparous women. The median time to advance by 1 cm exceeded 1 hour until 5 cm was reached in both nulliparous and multiparous women. Based on a 95th percentile threshold, nulliparous women may take up to 7 hours to progress from 4 to 5 cm and over 3 hours to progress from 5 to 6 cm. Median cumulative duration of labour indicates that nulliparous women admitted at 4 cm, 5 cm, and 6 cm reached 10 cm within an expected time frame if the dilatation rate was ≥ 1 cm/hour, but their corresponding 95th percentiles show that labour could last up to 14, 11, and 9 hours, respectively. Substantial differences exist between actual plots of labour progression of individual women and the 'average labour curves' derived from study population-level data. Exclusion of women with augmented labours from the study population resulted in slightly faster labour progression patterns. CONCLUSIONS: Cervical dilatation during labour in the slowest-yet-normal women can progress more slowly than the widely accepted benchmark of 1 cm/hour, irrespective of parity. Interventions to expedite labour to conform to a cervical dilatation threshold of 1 cm/hour may be inappropriate, especially when applied before 5 cm in nulliparous and multiparous women. Averaged labour curves may not truly reflect the variability associated with labour progression, and their use for decision-making in labour management should be de-emphasized.

Methodological development of tools to measure how women are treated during facility-based childbirth in four countries: labor observation and community survey.

BACKGROUND: Efforts to improve maternal health are increasingly focused on improving the quality of care provided to women at health facilities, including the promotion of respectful care and eliminating mistreatment of women during childbirth. A WHO-led multi-country research project aims to develop and validate two tools (labor observation and community survey) to measure how women are treated during facility-based childbirth. This paper describes the development process for these measurement tools, and how they were implemented in a multi-country study (Ghana, Guinea, Myanmar and Nigeria). METHODS: An iterative mixed-methods approach was used to develop two measurement tools. Methodological development was conducted in four steps: (1) initial tool development; (2) validity testing, item adjustment and piloting of paper-based tools; (3) conversion to digital, tablet-based tools; and (4) data collection and analysis. These steps included systematic reviews, primary qualitative research, mapping of existing tools, item consolidation, peer review by key stakeholders and piloting. RESULTS: The development, structure, administration format, and implementation of the labor observation and community survey tools are described. For the labor observations, a total of 2016 women participated: 408 in Nigeria, 682 in Guinea, and 926 in Ghana. For the community survey, a total of 2672 women participated: 561 in Nigeria, 644 in Guinea, 836 in Ghana, and 631 in Myanmar. Of the 2016 women who participated in the labor observations, 1536 women (76.2%) also participated in the community survey and have linked data: 779 in Ghana, 425 in Guinea, and 332 in Nigeria. CONCLUSIONS: An important step to improve the quality of maternity care is to understand the magnitude and burden of mistreatment across contexts. Researchers and healthcare providers in maternal health are encouraged to use and implement these tools, to inform the development of more women-centered, respectful maternity healthcare services. By measuring the prevalence of mistreatment of women during childbirth, we will be able to design and implement programs and policies to transform maternity services.

Risk factors for peripartum hysterectomy among women with postpartum haemorrhage: analysis of data from the WOMAN trial.

BACKGROUND: Peripartum hysterectomy can cause significant morbidity and mortality. Most studies of peripartum hysterectomy are from high income countries. This cohort study examined risk factors for peripartum hysterectomy using data from Africa, Asia, Europe and the Americas. METHODS: We used data from the World Maternal Antifibrinolytic (WOMAN) trial carried out in 193 hospitals in 21 countries. Peripartum hysterectomy was defined as hysterectomy within 6 weeks of delivery as a complication of postpartum haemorrhage. Univariable and multivariable random effects logistic regression models were used to analyse risk factors. A hierarchical conceptual framework guided our multivariable analysis. RESULTS: Five percent of women had a hysterectomy (1020/20,017). Haemorrhage from placenta praevia/accreta carried a higher risk of hysterectomy (17%) than surgical trauma/tears (5%) and uterine atony (3%). The adjusted odds ratio (AOR) for hysterectomy in women with placenta praevia/accreta was 3.2 (95% CI: 2.7-3.8), compared to uterine atony. The risk of hysterectomy increased with maternal age. Caesarean section was associated with fourfold higher odds of hysterectomy than vaginal delivery (AOR 4.3, 95% CI: 3.6-5.0). Mothers in Asia had a higher hysterectomy incidence (7%) than mothers in Africa (5%) (AOR: 1.2, 95% CI: 0.9-1.7). CONCLUSIONS: Placenta praevia/accreta is associated with a higher risk of peripartum hysterectomy. Other risk factors for hysterectomy are advanced maternal age, caesarean section and giving birth in Asia.

The impact of early outcome events on the effect of tranexamic acid in post-partum haemorrhage: an exploratory subgroup analysis of the WOMAN trial.

BACKGROUND: In severe post-partum haemorrhage, death can occur within hours of bleeding onset so interventions to control the bleeding must be given immediately. In clinical trials of treatments for life-threatening bleeding, established treatments are given priority and the trial treatment is usually given last. However, enrolling patients in whom severe maternal morbidity or death is imminent or inevitable at the time of randomisation may dilute the effects of a trial treatment. METHODS: We conducted an exploratory analysis of data from the WOMAN trial, an international, randomised placebo-controlled trial of the effects of tranexamic acid on death and surgical intervention in 20,060 women with post-partum haemorrhage. We assessed the impact of early maternal death or hysterectomy due to exsanguination on the effect of tranexamic acid on each of these respective outcomes. We conducted repeated analyses excluding patients with these outcomes at increasing intervals from the time of randomisation. We quantified treatment effects using risk ratios (RR) and 99% confidence intervals (CI) and prepared cumulative failure plots. RESULTS: Among 14,923 women randomised within 3 h of delivery (7518 tranexamic acid and 7405 placebo), there were 216 bleeding deaths (1.5%) and 383 hysterectomies due to bleeding (2.8%). After excluding deaths from exsanguination at increasing time intervals following randomization, there was a significant reduction in the risk of death due to bleeding with tranexamic acid (RR = 0.41; 99% CI 0.19-0.89). However, after excluding hysterectomies at increasing time intervals post-randomization, there was no reduction in the risk of hysterectomy due to bleeding with tranexamic acid (RR = 0.79; 99% CI 0.33-1.86). CONCLUSIONS: Findings from this analysis provide further evidence that tranexamic acid reduces the risk of death from exsanguination in women who experience postpartum haemorrhage. It is uncertain whether tranexamic acid reduces the risk of hysterectomy for bleeding after excluding early hysterectomies. TRIAL REGISTRATION: ISRCTN trial registration number ISRCTN76912190, 8 Dec 2008; ClinicalTrials.gov number NCT00872469, 30 March 2009; PACTR number PACTR201007000192283, 9 Feb 2010; EudraCT number 2008-008441-38, 8 Dec 2010 (retrospectively registered).

Haematological and fibrinolytic status of Nigerian women with post-partum haemorrhage.

BACKGROUND: Early treatment with tranexamic acid reduces deaths due to bleeding after post-partum haemorrhage. We report the prevalence of haematological, coagulation and fibrinolytic abnormalities in Nigerian women with postpartum haemorrhage. METHODS: We performed a secondary analysis of the WOMAN trial to assess laboratory data and rotational thromboelastometry (ROTEM) parameters in 167 women with postpartum haemorrhage treated at University College Hospital, Ibadan, Nigeria. We defined hyper-fibrinolysis as EXTEM maximum lysis (ML) > 15% on ROTEM. We defined coagulopathy as EXTEM clot amplitude at 5 min (A5) < 40 mm or prothrombin ratio > 1.5. RESULTS: Among the study cohort, 53 (40%) women had severe anaemia (haemoglobin< 70 g/L) and 17 (13%) women had severe thrombocytopenia (platelet count < 50 × 109/L). Thirty-five women (23%) had ROTEM evidence of hyper-fibrinolysis. Based on prothrombin ratio criteria, 16 (12%) had coagulopathy. Based on EXTEM A5 criteria, 49 (34%) had coagulopathy. CONCLUSION: Our findings suggest that, based on a convenience sample of women from a large teaching hospital in Nigeria, hyper-fibrinolysis may commonly occur in postpartum haemorrhage. Further mechanistic studies are needed to examine hyper-fibrinolysis associated with postpartum haemorrhage. Findings from such studies may optimize treatment approaches for postpartum haemorrhage. TRIAL REGISTRATION: The Woman trial was registered: NCT00872469; ISRCTN76912190 (Registration date: 22/03/2012).

The global maternal sepsis study and awareness campaign (GLOSS): study protocol.

BACKGROUND: Maternal sepsis is the underlying cause of 11% of all maternal deaths and a significant contributor to many deaths attributed to other underlying conditions. The effective prevention, early identification and adequate management of maternal and neonatal infections and sepsis can contribute to reducing the burden of infection as an underlying and contributing cause of morbidity and mortality. The objectives of the Global Maternal Sepsis Study (GLOSS) include: the development and validation of identification criteria for possible severe maternal infection and maternal sepsis; assessment of the frequency of use of a core set of practices recommended for prevention, early identification and management of maternal sepsis; further understanding of mother-to-child transmission of bacterial infection; assessment of the level of awareness about maternal and neonatal sepsis among health care providers; and establishment of a network of health care facilities to implement quality improvement strategies for better identification and management of maternal and early neonatal sepsis. METHODS: This is a facility-based, prospective, one-week inception cohort study. This study will be implemented in health care facilities located in pre-specified geographical areas of participating countries across the WHO regions of Africa, Americas, Eastern Mediterranean, Europe, South East Asia, and Western Pacific. During a seven-day period, all women admitted to or already hospitalised in participating facilities with suspected or confirmed infection during any stage of pregnancy through the 42nd day after abortion or childbirth will be included in the study. Included women will be followed during their stay in the facilities until hospital discharge, death or transfer to another health facility. The maximum intra-hospital follow-up period will be 42 days. DISCUSSION: GLOSS will provide a set of actionable criteria for identification of women with possible severe maternal infection and maternal sepsis. This study will provide data on the frequency of maternal sepsis and uptake of effective diagnostic and therapeutic interventions in obstetrics in different hospitals and countries. We will also be able to explore links between interventions and maternal and perinatal outcomes and identify priority areas for action.

Mistreatment of women during childbirth in Abuja, Nigeria: a qualitative study on perceptions and experiences of women and healthcare providers.

BACKGROUND: Global efforts have increased facility-based childbirth, but substantial barriers remain in some settings. In Nigeria, women report that poor provider attitudes influence their use of maternal health services. Evidence also suggests that women in Nigeria may experience mistreatment during childbirth; however, there is limited understanding of how and why mistreatment this occurs. This study uses qualitative methods to explore women and providers' experiences and perceptions of mistreatment during childbirth in two health facilities and catchment areas in Abuja, Nigeria. METHODS: In-depth interviews (IDIs) and focus group discussions (FGDs) were used with a purposive sample of women of reproductive age, midwives, doctors and facility administrators. Instruments were semi-structured discussion guides. Participants were asked about their experiences and perceptions of, and perceived factors influencing mistreatment during childbirth. Thematic analysis was used to synthesize findings into meaningful sub-themes, narrative text and illustrative quotations, which were interpreted within the context of this study and an existing typology of mistreatment during childbirth. RESULTS: Women and providers reported experiencing or witnessing physical abuse including slapping, physical restraint to a delivery bed, and detainment in the hospital and verbal abuse, such as shouting and threatening women with physical abuse. Women sometimes overcame tremendous barriers to reach a hospital, only to give birth on the floor, unattended by a provider. Participants identified three main factors contributing to mistreatment: poor provider attitudes, women's behavior, and health systems constraints. CONCLUSIONS: Moving forward, findings from this study must be communicated to key stakeholders at the study facilities. Measurement tools to assess how often mistreatment occurs and in what manner must be developed for monitoring and evaluation. Any intervention to prevent mistreatment will need to be multifaceted, and implementers should consider lessons learned from related interventions, such as increasing audit and feedback including from women, promoting labor companionship and encouraging stress-coping training for providers.

Use of antenatal corticosteroids and tocolytic drugs in preterm births in 29 countries: an analysis of the WHO Multicountry Survey on Maternal and Newborn Health.

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. ß-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.

WHO Better Outcomes in Labour Difficulty (BOLD) project: innovating to improve quality of care around the time of childbirth.

As most pregnancy-related deaths and morbidities are clustered around the time of childbirth, quality of care during this period is critical to the survival of pregnant women and their babies. Despite the wide acceptance of partograph as the central tool to optimize labour outcomes for over 40 years, its use has not successfully improved outcomes in many settings for several reasons. There are also increasing questions about the validity and applicability of its central feature - "the alert line" - to all women regardless of their labour characteristics. Apart from the known deficiencies in labour care, attempts to improve quality of care in low resource settings have also failed to address and integrate women's birth experience into quality improvement processes. It was against this background that the World Health Organization (WHO) embarked on the Better Outcomes in Labour Difficulty (BOLD) project to improve the quality of intrapartum care in low- and middle-income countries. The main goal of the BOLD project is to reduce intrapartum-related stillbirths, maternal and newborn mortalities and morbidities by addressing the critical barriers to the process of good quality intrapartum care and enhancing the connection between health systems and communities. The project seeks to achieve this goal by (1) developing an evidence-based, easy to use, labour monitoring-to-action decision-support tool (currently termed Simplified, Effective, Labour Monitoring-to-Action - SELMA); and (2) by developing innovative service prototypes/tools, co-designed with users of health services (women, their families and communities) and health providers, to promote access to respectful, dignified and emotionally supportive care for pregnant women and their companions at the time of birth ("Passport to Safer Birth"). This two-pronged approach is expected to positively impact on important domains of quality of care relating to both provision and experience of care. In this paper, we briefly describe the rationale for innovative thinking in relation to improving quality of care around the time of childbirth and introduce WHO current plans to improve care through research, design and implementation of innovative tools and services in the post-2015 era.Please see related articles ' http://dx.doi.org/10.1186/s12978-015-0029-4 ' and ' http://dx.doi.org/10.1186/s12978-015-0028-5 '.

Formative research and development of innovative tools for "Better Outcomes in Labour Difficulty" (BOLD): study protocol.

BACKGROUND: Most complications during labour and childbirth could be averted with timely interventions by skilled healthcare providers. Yet, the quality and outcomes of childbirth care remains suboptimal in many health facilities in low-resource settings. To accelerate the reduction of childbirth-related maternal, fetal and newborn mortality and morbidity, the World Health Organization has initiated the "Better Outcomes in Labour Difficulty" (BOLD) project to address weaknesses in labour care processes and better connect health systems and communities. The project seeks to develop a "Simplified, Effective, Labour Monitoring-to-Action" tool (SELMA) to assist healthcare providers to monitor labour and take decisive actions more efficiently; and by developing an innovative set of service prototypes and/or tools termed "Passport to Safer Birth", designed with communities and healthcare providers, to promote access to quality care for women during childbirth. This protocol describes the formative research activities to support the development of these tools. METHODS/DESIGN: We will employ qualitative research and service design methodologies in eight health facilities and their catchment communities in Nigeria and Uganda. In the health facilities, focus group discussions (FGD) and in-depth interviews (IDI) will be conducted among different cadres of healthcare providers and facility administrators. In the communities, FGDs and IDIs will be conducted among women who have delivered in a health facility. We will use service design methods to explore women's journey to access and receive childbirth care in order to innovate and design services around the needs and expectations of women, within the context of the health system. DISCUSSION: This formative research will serve several roles. First, it will provide an in-depth understanding of healthcare providers and health system issues to be accounted for in the final design and implementation of SELMA. Second, it will help to identify key moments ("touch points") where women's experiences of childbirth care are shaped, and where the overall experience of quality care could be improved. The synthesis of findings from the qualitative and service design activities will help identify potential areas for behaviour change related to the provision and experience of childbirth care, and serve as the basis for the development of Passport to Safer Birth. Please see related articles 'http://dx.doi.org/ 10.1186/s12978-015-0027-6 ' and 'http://dx.doi.org/ 10.1186/s12978-015-0029-4 '.

The development of a Simplified, Effective, Labour Monitoring-to-Action (SELMA) tool for Better Outcomes in Labour Difficulty (BOLD): study protocol.

BACKGROUND: The partograph is currently the main tool available to support decision-making of health professionals during labour. However, the rate of appropriate use of the partograph is disappointingly low. Apart from limitations that are associated with partograph use, evidence of positive impact on labour-related health outcomes is lacking. The main goal of this study is to develop a Simplified, Effective, Labour Monitoring-to-Action (SELMA) tool. The primary objectives are: to identify the essential elements of intrapartum monitoring that trigger the decision to use interventions aimed at preventing poor labour outcomes; to develop a simplified, monitoring-to-action algorithm for labour management; and to compare the diagnostic performance of SELMA and partograph algorithms as tools to identify women who are likely to develop poor labour-related outcomes. METHODS/DESIGN: A prospective cohort study will be conducted in eight health facilities in Nigeria and Uganda (four facilities from each country). All women admitted for vaginal birth will comprise the study population (estimated sample size: 7,812 women). Data will be collected on maternal characteristics on admission, labour events and pregnancy outcomes by trained research assistants at the participating health facilities. Prediction models will be developed to identify women at risk of intrapartum-related perinatal death or morbidity (primary outcomes) throughout the course of labour. These predictions models will be used to assemble a decision-support tool that will be able to suggest the best course of action to avert adverse outcomes during the course of labour. To develop this set of prediction models, we will use up-to-date techniques of prognostic research, including identification of important predictors, assigning of relative weights to each predictor, estimation of the predictive performance of the model through calibration and discrimination, and determination of its potential for application using internal validation techniques. DISCUSSION: This research offers an opportunity to revisit the theoretical basis of the partograph. It is envisioned that the final product would help providers overcome the challenging tasks of promptly interpreting complex labour information and deriving appropriate clinical actions, and thus increase efficiency of the care process, enhance providers' competence and ultimately improve labour outcomes. Please see related articles ' http://dx.doi.org/10.1186/s12978-015-0027-6 ' and ' http://dx.doi.org/10.1186/s12978-015-0028-5 '.

How women are treated during facility-based childbirth: development and validation of measurement tools in four countries - phase 1 formative research study protocol.

BACKGROUND: Every woman has the right to dignified, respectful care during childbirth. Recent evidence has demonstrated that globally many women experience mistreatment during labour and childbirth in health facilities, which can pose a significant barrier to women attending facilities for delivery and can contribute to poor birth experiences and adverse outcomes for women and newborns. However there is no clear consensus on how mistreatment of women during childbirth in facilities is defined and measured. We propose using a two-phased, mixed-methods study design in four countries to address these research gaps. This protocol describes the Phase 1 qualitative research activities. METHODS/DESIGN: We will employ qualitative research methodologies among women, healthcare providers and administrators in the facility catchment areas of two health facilities in each country: Ghana, Guinea, Myanmar and Nigeria. In-depth interviews (IDIs) and focus group discussions (FGDs) will be conducted among women of reproductive age (15-49 years) to explore their perceptions and experiences of facility-based childbirth care, focused on how they were treated by healthcare workers and perceived factors affecting how they were treated. IDIs will also be conducted with healthcare providers of different cadres (e.g.: nurses, midwives, medical officers, specialist obstetricians) and facility administrators working in the selected facilities to explore healthcare providers' perceptions and experiences of facility-based childbirth care and how staff are treated, colleagues and supervisors. Audio recordings will be transcribed and translated to English. Textual data will be analysed using a thematic framework approach and will consist of two levels of analysis: (1) conduct of local analysis workshops with the research assistants in each country; and (2) line-by-line coding to develop a thematic framework and coding scheme. DISCUSSION: This study serves several roles. It will provide an in-depth understanding of how women are treated during childbirth in four countries and perceived factors associated with this mistreatment. It will also provide data on where and how an intervention could be developed to reduce mistreatment and promote respectful care. The findings from this study will contribute to the development of tools to measure the prevalence of mistreatment of women during facility-based childbirth.

Moving beyond essential interventions for reduction of maternal mortality (the WHO Multicountry Survey on Maternal and Newborn Health): a cross-sectional study.

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.

Extra fluids for breastfeeding mothers for increasing milk production.

BACKGROUND: Breastfeeding is known to be the biological norm. Despite this, many women wean their babies because of perceived insufficient breast milk production. Mothers are sometimes advised to increase their fluid intake in the hope that this could improve breast milk production. The effect of extra fluid on human breast milk production is not well established, however. OBJECTIVES: To assess the effect of extra fluid for breastfeeding mothers on milk production/supply and infant growth. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (27 April 2014), MEDLINE (1966 to 27 April 2014), African Journals Online (27 April 2014) and reference lists of retrieved studies. SELECTION CRITERIA: Randomised controlled trials and quasi-randomised controlled trials on extra fluids for breastfeeding mothers. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the potential studies for inclusion and assessed trial quality. MAIN RESULTS: Five trial reports were retrieved using the search strategies. Four trials were excluded. We did not identify any randomised controlled trials for inclusion but we included one quasi-randomised study (involving 210 women) that evaluated the effect of extra fluid for breastfeeding mothers on breastfeeding outcomes. The study was considered to be at a high risk of bias. Only one of this review's primary outcomes was reported (breast milk production (as defined by the trialist)) but data were not in a suitable format for analysis (no standard deviations or standard errors were reported). The trialist reported that advising women to drink extra fluids did not improve breast milk production. No data were reported for the review's other primary outcomes: satisfactory weight gain in the infant (as defined by the trialists) and duration of exclusive breastfeeding (months). Similarly, no data were reported for any of this review's secondary outcomes: duration of any breastfeeding; mother's satisfaction with breastfeeding; hydration in mother; dehydration in the infant; or episodes of gastrointestinal illness. AUTHORS' CONCLUSIONS: This review only identified one small quasi-randomised controlled trial of low quality and high risk of bias. The study provided limited data on only one of this review's primary outcomes, breast milk production, but the data were not reported in a format that permitted further analysis. The trialist reported that extra fluids did not improve breast milk production. However, this outcome was measured by using test feeds (also known as test weighing). In the 1950s, when the study was conducted, it was common for babies in developed countries to be weighed before and after a feed, known as test weighing or test feeding. However, this practice is not now routinely practiced for term infants due to concerns about lack of precision as a measure of breast milk production. The included study did not report on this review's other primary outcomes (satisfactory weight gain in the infant or duration of exclusive breastfeeding) nor any of the review's secondary outcomes.The effect of additional fluids for breastfeeding mothers remains unknown, due to a lack of well-conducted trials. However, because the physiological basis for any such improvement remains unclear, the conduct of further clinical trials may not be a priority. There is not enough evidence to support an increased fluid intake beyond what breastfeeding mothers are likely to require to meet their physiological needs.

Maternal oxygen administration for fetal distress.

BACKGROUND: Maternal oxygen administration has been used in an attempt to lessen fetal distress by increasing the available oxygen from the mother. This has been used for suspected fetal distress during labour, and prophylactically during the second stage of labour on the assumption that the second stage is a time of high risk for fetal distress. OBJECTIVES: The objective of this review was to assess the effects of maternal oxygenation for fetal distress during labour and to assess the effects of prophylactic oxygen therapy during the second stage of labour on perinatal outcome. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (22 October 2012) and searched reference lists of retrieved studies. SELECTION CRITERIA: Randomized trials comparing maternal oxygen administration for fetal distress during labour and prophylactic oxygen administration during the second stage of labour with a control group (dummy or no oxygen therapy). DATA COLLECTION AND ANALYSIS: Both review authors assessed eligibility and trial quality. Data were extracted, checked and entered into Review Manager software. For dichotomous data, we calculated relative risks (RR) and 95% confidence intervals (CI). For continuous data, we calculated weighted mean differences and 95% CI. MAIN RESULTS: We located no trials addressing maternal oxygen therapy for fetal distress. We included two trials which addressed prophylactic oxygen administration during labour. Abnormal cord blood pH values (less than 7.2) were recorded significantly more frequently in the oxygenation group than the control group (RR 3.51, 95% CI 1.34 to 9.19). There were no other statistically significant differences between the groups. There were conflicting conclusions on the effect of the duration of oxygen administration on umbilical artery pH values between the two trials. AUTHORS' CONCLUSIONS: Implications for practice There is not enough evidence to support the use of prophylactic oxygen therapy for women in labour, nor to evaluate its effectiveness for fetal distress.Implications for research In view of the widespread use of oxygen administration during labour and the possibility that it may be ineffective or harmful, there is an urgent need for randomized trials to assess its effects.

Treatments for suppression of lactation.

BACKGROUND: Various pharmacologic and non-pharmacologic interventions have been used to suppress lactation after childbirth and relieve associated symptoms. Despite the large volume of literature on the subject, there is currently no universal guideline on the most appropriate approach for suppressing lactation in postpartum women. OBJECTIVES: To evaluate the effectiveness and safety of interventions used for suppression of lactation in postpartum women (who have not breastfed or expressed breastmilk) to determine which approach has the greatest comparative benefits with least risk. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 June 2012). SELECTION CRITERIA: Randomised trials evaluating the effectiveness of treatments used for suppression of postpartum lactation. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. MAIN RESULTS: We included 62 trials (6428 women). Twenty-two trials did not contribute data to the meta-analyses. The trials were generally small and of limited quality. Three trials (107 women) indicated that bromocriptine significantly reduced the proportion of women lactating compared with no treatment at or within seven days postpartum (three trials, 107 women; risk ratio (RR) 0.36, 95% confidence interval (CI) 0.24 to 0.54). Seven trials involving oestrogen preparations (diethylstilbestrol, quinestrol, chlorotrianisene, hexestrol) suggested that they significantly reduced the proportion of lactating women compared with no treatment at or within seven days postpartum (RR 0.40, 95% CI 0.29 to 0.56). We found no trials comparing non-pharmacologic methods with no treatment. Trials comparing bromocriptine with other pharmacologic agents such as methergoline, prostaglandins, pyridoxine, carbegoline, diethylstilbestrol and cyclofenil suggested similarity in their effectiveness. Side effects were poorly reported in the trials and no case of thromboembolism was recorded in the four trials that reported it as an outcome. AUTHORS' CONCLUSIONS: There is weak evidence that some pharmacologic treatments (most of which are currently unavailable to the public) are better than no treatment for suppressing lactation symptoms in the first postpartum week. No evidence currently exists to indicate whether non-pharmacologic approaches are more effective than no treatment. Presently, there is insufficient evidence to address the side effects of methods employed for suppressing lactation. When women desire treatment, bromocriptine may be considered where it is registered for lactation suppression in those without predisposition to its major side effects of public concerns. Many trials did not contribute data that could be included in analyses. Large randomised trials are needed to compare the effectiveness of pharmacologic (especially bromocriptine) and non-pharmacologic methods with no treatment. Such trials should consider the acceptability of the intervention and lactation symptoms of concern to women and be large enough to detect clinically important differences in major side effects between comparison groups.

Advance misoprostol distribution for preventing and treating postpartum haemorrhage.

BACKGROUND: Advance community distribution of misoprostol for preventing or treating postpartum haemorrhage (PPH) has become an attractive strategy to expand uterotonic coverage to places where conventional uterotonic use is not feasible. However, the value and safety of this strategy remain contentious. OBJECTIVES: To assess the effectiveness and safety of a strategy of advance misoprostol distribution for PPH prevention and treatment in non-facility births. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (5 October 2011). We did not apply any language restrictions. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials of advance misoprostol distribution to lay health workers or pregnant women compared with usual care for PPH prevention or treatment in non-facility births. We excluded studies without any form of random design. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial eligibility for inclusion. MAIN RESULTS: The search strategies identified three studies. None of the studies met the inclusion criteria. AUTHORS' CONCLUSIONS: There is no evidence from randomised or quasi-randomised trials on the benefits or risks of a strategy of advance misoprostol distribution for PPH prevention or treatment in non-facility births. In view of the increasing interest to scale up this strategy, there is an urgent need for large and well-designed randomised trials to evaluate its comparative benefits and risks.

The Log-Normal zero-inflated cure regression model for labor time in an African obstetric population.

In obstetrics and gynecology, knowledge about how women's features are associated with childbirth is important. This leads to establishing guidelines and can help managers to describe the dynamics of pregnant women's hospital stays. Then, time is a variable of great importance and can be described by survival models. An issue that should be considered in the modeling is the inclusion of women for whom the duration of labor cannot be observed due to fetal death, generating a proportion of times equal to zero. Additionally, another proportion of women's time may be censored due to some intervention. The aim of this paper was to present the Log-Normal zero-inflated cure regression model and to evaluate likelihood-based parameter estimation by a simulation study. In general, the inference procedures showed a better performance for larger samples and low proportions of zero inflation and cure. To exemplify how this model can be an important tool for investigating the course of the childbirth process, we considered the Better Outcomes in Labor Difficulty project dataset and showed that parity and educational level are associated with the main outcomes. We acknowledge the World Health Organization for granting us permission to use the dataset.