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BackgroundPoor representation of pregnant and lactating women and people in clinical trials has marginalised their health concerns and denied the maternal-fetal/infant dyad benefits of innovation in therapeutic research and development. This mixed-methods systematic review synthesised factors affecting the participation of pregnant and lactating women in clinical trials, across all levels of the research ecosystem.Methods and findingsWe searched 8 databases from inception to 14 February 2024 to identify qualitative, quantitative, and mixed-methods studies that described factors affecting participation of pregnant and lactating women in vaccine and therapeutic clinical trials in any setting. We used thematic synthesis to analyse the qualitative literature and assessed confidence in each qualitative review finding using the GRADE-CERQual approach. We compared quantitative data against the thematic synthesis findings to assess areas of convergence or divergence. We mapped review findings to the Theoretical Domains Framework (TDF) and Capability, Opportunity, and Motivation Model of Behaviour (COM-B) to inform future development of behaviour change strategies. We included 60 papers from 27 countries. We grouped 24 review findings under 5 overarching themes: (a) interplay between perceived risks and benefits of participation in women's decision-making; (b) engagement between women and the medical and research ecosystems; (c) gender norms and decision-making autonomy; (d) factors affecting clinical trial recruitment; and (e) upstream factors in the research ecosystem. Women's willingness to participate in trials was affected by: perceived risk of the health condition weighed against an intervention's risks and benefits, therapeutic optimism, intervention acceptability, expectations of receiving higher quality care in a trial, altruistic motivations, intimate relationship dynamics, and power and trust in medicine and research. Health workers supported women's participation in trials when they perceived clinical equipoise, had hope for novel therapeutic applications, and were convinced an intervention was safe. For research staff, developing reciprocal relationships with health workers, having access to resources for trial implementation, ensuring the trial was visible to potential participants and health workers, implementing a woman-centred approach when communicating with potential participants, and emotional orientations towards the trial were factors perceived to affect recruitment. For study investigators and ethics committees, the complexities and subjectivities in risk assessments and trial design, and limited funding of such trials contributed to their reluctance in leading and approving such trials. All included studies focused on factors affecting participation of cisgender pregnant women in clinical trials; future research should consider other pregnancy-capable populations, including transgender and nonbinary people.ConclusionsThis systematic review highlights diverse factors across multiple levels and stakeholders affecting the participation of pregnant and lactating women in clinical trials. By linking identified factors to frameworks of behaviour change, we have developed theoretically informed strategies that can help optimise pregnant and lactating women's engagement, participation, and trust in such trials.

Uterotonics are essential in preventing postpartum hemorrhage (PPH), the leading direct cause of maternal death worldwide. However, uterotonics are often substandard in low- and middle-income countries, contributing to poor maternal health outcomes. This study examines the health and economic impact of substandard uterotonics in Ghana. A decision-tree model was built to simulate vaginal and cesarean section births across health facilities, uterotonic quality and utilization, PPH risk and diagnosis, and resulting health and economic outcomes. We utilized delivery data from Ghana's maternal health survey, risks of health outcomes from a Cochrane review, and E-MOTIVE trial data for health outcomes related to oxytocin quality. We compared scenarios with and without substandard uterotonics, as well as scenarios altering uterotonic use and care-seeking behaviors. We found that substandard uterotonic use contributes to $18.8 million in economic burden annually, including $6.3 million and $4.8 million in out-of-pocket expenditures in public and private sectors, respectively. Annually, the National Health Insurance Scheme bears $1.6 million in costs due to substandard uterotonic use. Substandard uterotonics contribute to $6 million in long-term productivity losses from maternal mortality annually. Improving the quality of uterotonics could reduce 20,000 (11%) PPH cases, 5,000 (11%) severe PPH cases, and 100 (11%) deaths due to PPH annually in Ghana. Ensuring the quality of uterotonics would result in millions of dollars in cost savings and improve maternal health outcomes for the government and families in Ghana. Cost savings from improving uterotonic quality would provide financial protection and help Ghana advance toward Universal Health Coverage.

Abstract Background There are few medicines in clinical use for managing preterm labor or preventing spontaneous preterm birth from occurring. We previously developed two target product profiles (TPPs) for medicines to prevent spontaneous preterm birth and manage preterm labor. The objectives of this study were to 1) analyse the research and development pipeline of medicines for preterm birth and 2) compare these medicines to target product profiles for spontaneous preterm birth to identify the most promising candidates. Methods Adis Insight, Pharmaprojects, WHO international clinical trials registry platform (ICTRP), PubMed and grant databases were searched to identify candidate medicines (including drugs, dietary supplements and biologics) and populate the Accelerating Innovations for Mothers (AIM) database. This database was screened for all candidates that have been investigated for preterm birth. Candidates in clinical development were ranked against criteria from TPPs, and classified as high, medium or low potential. Preclinical candidates were categorised by product type, archetype and medicine subclass. Results The AIM database identified 178 candidates. Of the 71 candidates in clinical development, ten were deemed high potential (Prevention: Omega-3 fatty acid, aspirin, vaginal progesterone, oral progesterone, L-arginine, and selenium; Treatment: nicorandil, isosorbide dinitrate, nicardipine and celecoxib) and seven were medium potential (Prevention: pravastatin and lactoferrin; Treatment: glyceryl trinitrate, retosiban, relcovaptan, human chorionic gonadotropin and Bryophyllum pinnatum extract). 107 candidates were in preclinical development. Conclusions This analysis provides a drug-agnostic approach to assessing the potential of candidate medicines for spontaneous preterm birth. Research should be prioritised for high-potential candidates that are most likely to meet the real world needs of women, babies, and health care professionals.

Abstract Background The Accelerating Innovation for Mothers (AIM) project established a database of candidate medicines in research and development (R&D) between 2000 and 2021 for five pregnancy-related conditions, including pre-eclampsia. In parallel, we published target product profiles (TPPs) that describe optimal characteristics of medicines for use in preventing/treating pre-eclampsia. The study objective was to use systematic double screening and extraction to identify all candidate medicines being investigated for pre-eclampsia prevention/treatment and rank their potential based on the TPPs. Methods Adis Insight, Pharmaprojects, WHO international clinical trials registry platform (ICTRP), PubMed and grant databases were searched (Jan–May 2021). The AIM database was screened for all candidates being investigated for pre-eclampsia. Candidates in clinical development were evaluated against nine prespecified criteria from TPPs identified as key for wide-scale implementation, and classified as high, medium or low potential based on matching to the TPPs. Preclinical candidates were categorised by product type, archetype and medicine subclass. Results The AIM database identified 153 candidates for pre-eclampsia. Of the 87 candidates in clinical development, seven were classified as high potential (prevention: esomeprazole, l-arginine, chloroquine, vitamin D and metformin; treatment: sulfasalazine and metformin) and eight as medium potential (prevention: probiotic lactobacilli, dalteparin, selenium and omega-3 fatty acid; treatment: sulforaphane, pravastatin, rosuvastatin and vitamin B3). Sixty-six candidates were in preclinical development, the most common being amino acid/peptides, siRNA-based medicines and polyphenols. Conclusions This is a novel, evidence-informed approach to identifying promising candidates for pre-eclampsia prevention and treatment — a vital step in stimulating R&D of new medicines for pre-eclampsia suitable for real-world implementation.

Objective To identify current and emerging self-care interventions to improve maternity healthcare.Design Scoping review.Data sources MEDLINE, Embase, EmCare, PsycINFO, Cochrane CENTRAL/CDSR, CINAHL Plus (last searched on 17 October 2021).Eligibility criteria Evidence syntheses, interventional or observational studies describing any tool, resource or strategy to facilitate self-care in women preparing to get pregnant, currently pregnant, giving birth or post partum.Data extraction/synthesis Screening and data collection were conducted independently by two reviewers. Self-care interventions were identified based on predefined criteria and inductively organised into 11 categories. Characteristics of study design, interventions, participants and outcomes were recorded.Results We identified eligible 580 studies. Many included studies evaluated interventions in high-income countries (45%) and during antenatal care (76%). Self-care categories featuring highest numbers of studies were diet and nutrition (26% of all studies), physical activity (24%), psychosocial strategies (18%) and other lifestyle adjustments (17%). Few studies featured self-care interventions for sexual health and postpartum family planning (2%), self-management of medication (3%) and self-testing/sampling (3%). Several venues to introduce self-care were described: health facilities (44%), community venues (14%), digital platforms (18%), partner/peer support (7%) or over-the-counter products (13%). Involvement of health and community workers were described in 38% and 8% of studies, who supported self-care interventions by providing therapeutics for home use, training or counselling. The most common categories of outcomes evaluated were neonatal outcomes (eg, birth weight) (31%), maternal mental health (26%) and labour outcomes (eg, duration of labour) (22%).Conclusion Self-care interventions in maternal care are diverse in their applications, implementation characteristics and intended outcomes. Many self-care interventions were implemented with support from the health system at initial stages of use and uptake. Some promising self-care interventions require further primary research, though several are matured and up-to-date evidence syntheses are needed. Research on self-care in the preconception period is lacking.

Abstract The World Health Organization 2019 WHO consolidated guideline on self-care interventions for health: sexual and reproductive health and rights includes recommendations on self-administration of injectable contraception, over-the-counter (OTC) oral contraception and self-management of medical abortion. A review of the regulatory status of these two self-care interventions can highlight processes required to ensure that the quality of the medicines and safety of individuals are safeguarded in the introduction and scale-up in countries. This review outlines the legal regulatory status of prescription-only medicine (POM) and OTC contraceptives, including emergency contraception, and drugs for medical abortion in Egypt, Jordan, Lebanon, Morocco and Tunisia using information obtained from internet searches, regulatory information databases and personal contacts. In addition, the review examines whether the national medicines regulatory authorities have documented procedures available to allow for a change in status from a POM to OTC to allow for increased accessibility, availability and uptake of self-care interventions recommended by WHO. Egypt, Jordan and Lebanon have a documented national OTC list available. The only contraceptive product mentioned in the OTC lists across all five countries is ellaOne (ulipristal acetate for emergency contraception), which is publicly registered in Lebanon. None of the five countries has an official documented procedure to apply for the change of POM to OTC. Informal procedures exist, such as the ability to apply to the national medicines regulatory authority for OTC status if the product has OTC status in the original country of manufacture. However, many of these procedures are not officially documented, highlighting the need for establishing sound, affordable and effective regulation of medical products as an important part of health system strengthening. From a public health perspective, it would be advantageous for licensed products to be available OTC. This is particularly the case for settings where the health system is under-resourced or over-stretched due to health emergencies. Readiness of national regulatory guidelines and OTC procedures could lead to increased access, availability and usage of essential self-care interventions for sexual and reproductive health and rights.

Abstract Objective Access to quality, effective lifesaving uterotonics in low and middle-income countries (LMICs) remains a major barrier to reducing maternal deaths from postpartum haemorrhage (PPH). Our objective was to assess the costs of care for women who receive different preventative uterotonics, and with PPH and no-PPH so that the differences, if significant, can inform better resource allocation for maternal health care. Methods The costs of direct hospital care of women who received oxytocin or heat-stable carbetocin for prevention of PPH in selected tertiary care facilities in India, Kenya, Nigeria, and Uganda were assessed. We collected data from all women who had PPH, as well as a random sample of women without PPH. Cost data was collected for the cost of stay, PPH interventions, transfusions and medications for 2966 women. We analyzed the difference in cost of care at a facility level between women who experienced a PPH event and those who did not. Key findings The mean cost of care of a woman experiencing PPH in the study sites in India, Kenya, Nigeria, and Uganda exceeded the cost of care of a woman who did not experience PPH by between 21% and 309%. There was a large variation in cost across hospitals within a country and across countries. Conclusion Our results quantify the increased cost of PPH of up to 4.1 times that for a birth without PPH. PPH cost information can help countries to evaluate options across different conditions and in the formulation of appropriate guidelines for intrapartum care, including rational selection of quality-assured, effective medicines. This information can be applied to national assessment and adaptation of international recommendations such as the World Health Organization’s recommendations on uterotonics for the prevention of PPH or other interventions used to treat PPH. Trial registration HRP Trial A65870; UTN U1111-1162-8519; ACTRN12614000870651; CTRI/2016/05/006969, EUDRACT 2014–004445-26. Date of registration 14 August 2014 Plain English summary Access to quality, effective lifesaving medicines in low and middle-income countries remains a major barrier to reducing maternal deaths from bleeding after childbirth. Information on to what extent treatments for bleeding increases the cost of care of women after childbirth is important for informed resource allocation. We collected data from all women who had bleeding after childbirth, as well as a random sample of women without bleeding in selected hospitals in India, Kenya, Nigeria, and Uganda. Cost data was collected for the cost of stay and interventions to manage bleeding for 2966 women. We compared the difference in cost of care between women who experienced a bleeding event and those who did not. The mean cost of care of a woman with bleeding in the study sites exceeded the cost of care of a woman who did not experience PPH by between 21% and 309%. There was a large variation in cost across hospitals within a country and across countries. Our results indicate an increased cost of bleeding of up to 4.1 times that for birth without bleeding. Effective prevention reduces the cost of care. Cost information can help countries to evaluate options across different conditions and in the formulation of appropriate guidelines for intrapartum care, including rational selection of quality-assured, effective medicines. This information can be applied to national assessment and adaptation of international recommendations such as the World Health Organization’s recommendations on medications for the prevention of bleeding after childbirth or other interventions used to treat bleeding.

Abstract Objective Understanding the price components of the mifepristone/misoprostol (combi-pack) for medical abortion to improve access is critical for identifying strategies to reduce product costs for quality-assured formulations and expanding its availability and use. Methods We constructed a cost of goods sold analysis using data collected from manufacturing companies in Bangladesh, China and India supported by publicly available information related to the product formulation, active pharmaceutical ingredients (API), manufacturing location, manufacturer profiles and other individual model components. Key model components were the active pharmaceutical ingredients (quality-assured or not), excipients, labour cost, operating cost and packaging. Results Combi-pack direct production cost ranges from US$1.08 for finished products which are not quality assured to US$3.05 for products containing quality assured active pharmaceutical ingredients, which means that with a 30% administrative fee applied to those prices, it could be made available between US$1.40 and US$3.97 depending on location, manufacturer’s profile, optimal market situation and the quality of the active pharmaceutical ingredients. The main model component impacting on the cost range is the purchase price of mifepristone active pharmaceutical ingredient and the current differential between quality-assured material supported by adequate documentation and API for which quality assurance cannot be demonstrated. Compared to India cost of goods sold is lower in Bangladesh primarily due to lower operating costs, including the cost of labour. Conclusions It is feasible to lower the cost of quality-assured combi-packs, through reducing mifepristone API cost and selection of the manufacturing location. However, manufacturers need to be incentivised to achieve WHO pre-qualification with a carefully built business case and require support in identifying and sourcing competitively priced material and manufacturing products to the necessary standard.

Abstract Background To identify risk factors associated with a composite adverse maternal outcomes in women undergoing intrapartum cesarean birth. Methods We used the facility-based, multi-country, cross-sectional WHO Global Survey of Maternal and Perinatal Health (2004–2008) to examine associations between woman-, labor/obstetric-, and facility-level characteristics and a composite adverse maternal outcome of postpartum morbidity and mortality. This analysis was performed among women who underwent intrapartum cesarean birth during the course of labor. Results We analyzed outcomes of 29,516 women from low- and middle-income countries who underwent intrapartum cesarean birth between the gestational ages of 24 and 43 weeks, 3.5% (1040) of whom experienced the composite adverse maternal outcome. In adjusted analyses, factors associated with a decreased risk of the adverse maternal outcome associated with intrapartum cesarean birth included having four or more antenatal visits (AOR 0.60; 95% CI: 0.43–0.84; p = 0.003), delivering in a medium- or high-human development index country (vs. low-human development index country: AOR 0.07; 95% CI: 0.01–0.85 and AOR 0.02; 95% CI: 0.001–0.39, respectively; p = 0.03), and malpresentation (vs. cephalic: breech AOR 0.52; CI: 0.31–0.87; p = 0.04). Women who were medically high risk (vs. not medically high risk: AOR 1.81; CI: 1.30–2.51, p

BackgroundPreeclampsia and eclampsia are a leading cause of global maternal and newborn mortality. Currently, there are few effective medicines that can prevent or treat preeclampsia. Target Product Profiles (TPPs) are important tools for driving new product development by specifying upfront the characteristics that new products should take. Considering the lack of investment and innovation around new medicines for obstetric conditions, we aimed to develop two new TPPs for medicines to prevent and treat preeclampsia.Methods and findingsWe used a multi-methods approach comprised of a literature review, stakeholder interviews, online survey, and public consultation. Following an initial literature review, diverse stakeholders (clinical practice, research, academia, international organizations, funders, consumer representatives) were invited for in-depth interviews and an online international survey, as well as public consultation on draft TPPs. The level of stakeholder agreement with TPPs was assessed, and findings from interviews were synthesised to inform the final TPPs. We performed 23 stakeholder interviews and received 46 survey responses. A high level of agreement was observed in survey results, with 89% of TPP variables reaching consensus (75% agree or strongly agree). Points of discussion were raised around the target population for preeclampsia prevention and treatment, as well as the acceptability of cold-chain storage and routes of administration.ConclusionThere is consensus within the maternal health research community on the parameters that new medicines for preeclampsia prevention and treatment must achieve to meet real-world health needs. These TPPs provide necessary guidance to spur interest, innovation and investment in the development of new medicines to prevent and treat preeclampsia.

Background Preeclampsia and eclampsia are a leading cause of global maternal and newborn mortality. Currently, there are few effective medicines that can prevent or treat preeclampsia. Target Product Profiles (TPPs) are important tools for driving new product development by specifying upfront the characteristics that new products should take. Considering the lack of investment and innovation around new medicines for obstetric conditions, we aimed to develop two new TPPs for medicines to prevent and treat preeclampsia. Methods and findings We used a multi-methods approach comprised of a literature review, stakeholder interviews, online survey, and public consultation. Following an initial literature review, diverse stakeholders (clinical practice, research, academia, international organizations, funders, consumer representatives) were invited for in-depth interviews and an online international survey, as well as public consultation on draft TPPs. The level of stakeholder agreement with TPPs was assessed, and findings from interviews were synthesised to inform the final TPPs. We performed 23 stakeholder interviews and received 46 survey responses. A high level of agreement was observed in survey results, with 89% of TPP variables reaching consensus (75% agree or strongly agree). Points of discussion were raised around the target population for preeclampsia prevention and treatment, as well as the acceptability of cold-chain storage and routes of administration. Conclusion There is consensus within the maternal health research community on the parameters that new medicines for preeclampsia prevention and treatment must achieve to meet real-world health needs. These TPPs provide necessary guidance to spur interest, innovation and investment in the development of new medicines to prevent and treat preeclampsia.

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.

Abstract Self-care interventions and remote care offer innovative and equitable ways to strengthen access to sexual and reproductive health services. Self-isolation during COVID-19 provided the opportunity for obstetric facilities and healthcare providers to integrate and increase the usage of interventions for self-care and remote care for pregnant women and to improve the quality of care overall.

Abstract Background 2500 g has been used worldwide as the definition of low birthweight (LBW) for almost a century. While previous studies have used statistical approaches to define LBW cutoffs, a LBW definition using an outcome-based approach has not been evaluated. We aimed to identify an outcome-based definition of LBW for live births in low- and middle-income countries (LMICs), using data from a WHO cross-sectional survey on maternal and perinatal health outcomes in 23 countries. Methods We performed a secondary analysis of all singleton live births in the WHO Global Survey (WHOGS) on Maternal and Perinatal Health, conducted in African and Latin American countries (2004–2005) and Asian countries (2007–2008). We used a two-level logistic regression model to assess the risk of early neonatal mortality (ENM) associated with subgroups of birthweight (

Abstracto Antecedentes La pérdida de grandes cantidades de sangre después del parto puede llevar a morbilidad y mortalidad materna severas. Entender la naturaleza de la pérdida de sangre postparto es crítico para el desarrollo de técnicas de análisis eficientes cuando se comparan tratamientos para prevenir este evento. Cuando se mide la pérdida de sangre, que resulta en una variable continua, frecuentemente esta variable se categoriza en clases y se reduce a un indicador de volumen mayor que un cierto punto de corte. Esta reducción del volumen a categorías conlleva una pérdida sustancial de información. En consecuencia, son necesarios ensayos muy grandes para evaluar diferencias clínicamente importantes entre tratamientos de prevención de hemorragia postparto. Métodos Los autores examinan la naturaleza de la distribución de pérdida de sangre postparto, suponiendo que las propiedades físicas de la pérdida de sangre resultan en una distribución lognormal. Los datos de cuatro ensayos clínicos y de un estudio observacional se usan como confirmación empírica. Las estimaciones de la probabilidad del evento hemorragia postparto ‘pérdida de sangre mayor que un cierto punto de corte’ y riesgos relativos se obtienen del ajuste de las distribuciones lognormales. Los intervalos de confianza para el riesgo relativo se obtienen usando técnicas de bootstrap. Resultados Una variante de la distribución lognormal, la distribución lognormal con tres parámetros, produjo un excelente ajuste a los datos de pérdida de sangre postparto para los cuatro ensayos y para el estudio observacional. Una evaluación de la calidad de las medidas mostró que problemas de preferencia de dígito y de límite mínimo de detección eran bien controlados por el ajuste lognormal. El análisis del evento hemorragia postparto basado en la distribución lognormal mejoró la eficiencia de las estimaciones. El cálculo de tamaño de muestra para un futuro ensayo hipotético mostró que la aplicación de este procedimiento permite reducir el tamaño de muestra requerido para comparar tratamientos. Conclusión Una variante de la distribución lognormal ajustó muy bien a los datos de pérdida de sangre postparto de diferentes áreas geográficas, sugiriendo que la distribución lognormal podría ajustar a la pérdida de sangre postparto universalmente. Una estrategia de análisis para los eventos de hemorragia postparto basada en la distribución lognormal mejora la eficiencia de las estimaciones de probabilidades y de riesgo relativo, y permite una reducción del tamaño de muestra para comparar tratamientos. Registro de los ensayos Este artículo reporta análisis secundarios para ensayos registrados en los siguientes registros: Australian New Zealand Clinical Trials Registry (ACTRN 12608000434392 y ACTRN12614000870651); clinicaltrials.gov (NCT00781066).

Abstract 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.

Summary: Background: Amid efforts to improve the quality of care for women and neonates during childbirth, there is growing interest in the experience of care, including respectful care practices. However, there is little research on the prevalence of practices that might constitute mistreatment of neonates. This study aims to describe the care received by neonates up to 2 h after birth in a sample of three countries in west Africa. Methods: Data from this multicountry, facility-based, observational study were collected on 15 neonatal care practices across nine facilities in Ghana, Guinea, and Nigeria, as part of WHO's wider multicountry study on how women are treated during childbirth. Women were eligible if they were admitted to the participating health facilities for childbirth, in early established labour or active labour, aged 15 years or older, and provided written informed consent on behalf of themselves and their neonate. All labour observations were continuous, one-to-one observations of women and neonates by independent data collectors. Descriptive statistics and multivariate logistic regressions were used to examine associations between these neonatal care practices, maternal and neonate characteristics, and maternal mistreatment. Early neonate deaths, stillbirths, and higher order multiple births were excluded from analysis. Findings: Data collection took place from Sept 19, 2016, to Feb 26, 2017, in Nigeria; from Aug 1, 2017, to Jan 18, 2018, in Ghana; and from July 1 to Oct 30, 2017, in Guinea. We included data for 362 women–neonate dyads (356 [98%] with available data for neonatal care practices) in Nigeria, 760 (749 [99%]) in Ghana, and 558 (522 [94%]) in Guinea. Delayed cord clamping was done for most neonates (1493 [91·8%] of 1627); other practices, such as skin-to-skin contact, were less commonly done (1048 [64·4%]). During the first 2 h after birth, separation of the mother and neonate occurred in 844 (51·9%) of 1627 cases; and was more common for mothers who were single (adjusted odds ratio [AOR; adjusting for country, maternal age, education, marital status, neonate weight at birth, and neonate sex] 1·8, 95% CI 1·3–2·6) than those who were married or cohabiting. Lack of maternal education was associated with increased likelihood of neonates not receiving recommended breastfeeding practices. Neonates with a low birthweight (

Introduction Complications due to unsafe abortions are an important cause of morbidity and mortality in many sub-Saharan African countries. We aimed to characterise abortion-related complication severity, describe their management, and to report women’s experience of abortion care in Africa.Methods A cross-sectional study was implemented in 210 health facilities across 11 sub-Saharan African countries. Data were collected on women’s characteristics, clinical information and women’s experience of abortion care (using the audio computer-assisted self-interviewing (ACASI) system). Severity of abortion complications were organised in five hierarchical mutually exclusive categories based on indicators present at assessment. Descriptive bivariate analysis was performed for women’s characteristics, management of complications and reported experiences of abortion care by severity. Generalised linear estimation models were used to assess the association between women’s characteristics and severity of complications.Results There were 13 657 women who had an abortion-related complication: 323 (2.4%) women were classified with severe maternal outcomes, 957 (7.0%) had potentially life-threatening complications, 7953 (58.2%) had moderate complications and 4424 (32.4%) women had mild complications. Women who were single, multiparous, presenting ≥13 weeks of gestational age and where expulsion of products of conception occurred prior to arrival to facility were more likely to experience severe complications. For management, the commonly used mechanical methods of uterine evacuation were manual vacuum aspiration (76.9%), followed by dilation and curettage (D&C) (20.1%). Most frequently used uterotonics were oxytocin (50∙9%) and misoprostol (22.7%). Via ACASI, 602 (19.5%) women reported having an induced abortion. Of those, misoprostol was the most commonly reported method (54.3%).Conclusion There is a critical need to increase access to and quality of evidence-based safe abortion, postabortion care and to improve understanding around women’s experiences of abortion care.

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

The use of substandard and counterfeit medicines (SCM) leads to significant health and economic consequences, like treatment failure, rise of antimicrobial resistance, extra expenditures of individuals or households and serious adverse drug reactions including death. Our objective was to systematically search, identify and compare relevant available mobile applications (apps) for smartphones and tablets, which use could potentially affect clinical and public health outcomes. We carried out a systematic review of the literature in January 2020, including major medical databases, and app stores. We used the validated Mobile App Rating Scale (MARS) to assess the quality of apps, (1 worst score, 3 acceptable score, and 5 best score). We planned to evaluate the accuracy of the mobile apps to detect SCM. We retrieved 335 references through medical databases and 42 from Apple, Google stores and Google Scholar. We finally included two studies of the medical database, 25 apps (eight from the App Store, eight from Google Play, eight from both stores, and one from Google Scholar), and 16 websites. We only found one report on the accuracy of a mobile apps detecting SCMs. Most apps use the imprint, color or shape for pill identification, and only a few offer pill detection through photographs or bar code. The MARS mean score for the apps was 3.17 (acceptable), with a maximum of 4.9 and a minimum of 1.1. The 'functionality' dimension resulted in the highest mean score (3.4), while the 'engagement' and 'information' dimensions showed the lowest one (3.0). In conclusion, we found a remarkable evidence gap about the accuracy of mobile apps in detecting SCMs. However, mobile apps could potentially be useful to screen for SCM by assessing the physical characteristics of pills, although this should still be assessed in properly designed research studies.

Objective To evaluate changes in awareness of maternal sepsis among healthcare providers resulting from the WHO Global Maternal Sepsis Study (GLOSS) awareness campaign.Design Independent sample precampaign/postcampaign through online and paper-based surveys available for over 30 days before campaign roll-out (pre) and after study data collection (post). Descriptive statistics were used for campaign recognition and exposure, and odds ratio (OR) and percentage change were calculated for differences in awareness, adjusting for confounders using multivariate logistic regression.Setting and participants Healthcare providers from 398 participating facilities in 46 low, middle and high-income countries.Intervention An awareness campaign to accompany GLOSS launched 3 weeks prior to data collection and lasting the entire study period (28 November 2017 to 15 January 2018) and beyond.Main outcome measures Campaign recognition and exposure, and changes in awareness.Results A total of 2188 surveys were analysed: 1155 at baseline and 1033 at postcampaign. Most survey respondents found the campaign materials helpful (94%), that they helped increase awareness (90%) and that they helped motivate to act differently (88%). There were significant changes with regard to: not having heard of maternal sepsis (−63.4% change, pre-OR/post-OR 0.35, 95% CI 0.18 to 0.68) and perception of confidence in making the right decisions with regard to maternal sepsis identification and management (7.3% change, pre-OR/post-OR 1.44, 95% CI 1.01 to 2.06).Conclusions Awareness raising campaigns can contribute to an increase in having heard of maternal sepsis and an increase in provider perception of confidence in making correct decisions. Offering the information to make accurate and timely decisions while promoting environments that enable self-confidence and support could improve maternal sepsis identification and management.

Summary: Background: Maternal infections are an important cause of maternal mortality and severe maternal morbidity. We report the main findings of the WHO Global Maternal Sepsis Study, which aimed to assess the frequency of maternal infections in health facilities, according to maternal characteristics and outcomes, and coverage of core practices for early identification and management. Methods: We did a facility-based, prospective, 1-week inception cohort study in 713 health facilities providing obstetric, midwifery, or abortion care, or where women could be admitted because of complications of pregnancy, childbirth, post-partum, or post-abortion, in 52 low-income and middle-income countries (LMICs) and high-income countries (HICs). We obtained data from hospital records for all pregnant or recently pregnant women hospitalised with suspected or confirmed infection. We calculated ratios of infection and infection-related severe maternal outcomes (ie, death or near-miss) per 1000 livebirths and the proportion of intrahospital fatalities across country income groups, as well as the distribution of demographic, obstetric, clinical characteristics and outcomes, and coverage of a set of core practices for identification and management across infection severity groups. Findings: Between Nov 28, 2017, and Dec 4, 2017, of 2965 women assessed for eligibility, 2850 pregnant or recently pregnant women with suspected or confirmed infection were included. 70·4 (95% CI 67·7–73·1) hospitalised women per 1000 livebirths had a maternal infection, and 10·9 (9·8–12·0) women per 1000 livebirths presented with infection-related (underlying or contributing cause) severe maternal outcomes. Highest ratios were observed in LMICs and the lowest in HICs. The proportion of intrahospital fatalities was 6·8% among women with severe maternal outcomes, with the highest proportion in low-income countries. Infection-related maternal deaths represented more than half of the intrahospital deaths. Around two-thirds (63·9%, n=1821) of the women had a complete set of vital signs recorded, or received antimicrobials the day of suspicion or diagnosis of the infection (70·2%, n=1875), without marked differences across severity groups. Interpretation: The frequency of maternal infections requiring management in health facilities is high. Our results suggest that contribution of direct (obstetric) and indirect (non-obstetric) infections to overall maternal deaths is greater than previously thought. Improvement of early identification is urgently needed, as well as prompt management of women with infections in health facilities by implementing effective evidence-based practices. Funding: UNDP–UNFPA–UNICEF–WHO–World Bank Special Programme of Research, Development and Research Training in Human Reproduction, WHO, Merck for Mothers, and United States Agency for International Development.

Abstract Background A prolonged and complicated second stage of labour is associated with serious perinatal complications. The Odon device is an innovation intended to perform instrumental vaginal delivery presently under development. We present an evaluation of the feasibility and safety of delivery with early prototypes of this device from an early terminated clinical study. Methods Hospital-based, multi-phased, open-label, pilot clinical study with no control group in tertiary hospitals in Argentina and South Africa. Multiparous and nulliparous women, with uncomplicated singleton pregnancies, were enrolled during the third trimester of pregnancy. Delivery with Odon device was attempted under non-emergency conditions during the second stage of labour. The feasibility outcome was delivery with the Odon device defined as successful expulsion of the fetal head after one-time application of the device. Results Of the 49 women enrolled, the Odon device was inserted successfully in 46 (93%), and successful Odon device delivery as defined above was achieved in 35 (71%) women. Vaginal, first and second degree perineal tears occurred in 29 (59%) women. Four women had cervical tears. No third or fourth degree perineal tears were observed. All neonates were born alive and vigorous. No adverse maternal or infant outcomes were observed at 6-weeks follow-up for all dyads, and at 1 year for the first 30 dyads. Conclusions Delivery using the Odon device is feasible. Observed genital tears could be due to the device or the process of delivery and assessment bias. Evaluating the effectiveness and safety of the further developed prototype of the BD Odon Device™ will require a randomized-controlled trial. Trial registration ANZCTR ACTRN12613000141741 Registered 06 February 2013. Retrospectively registered.

Résumé Contexte: Le sepsis maternel est la cause sous-jacente de 11% des décès maternels et un facteur contributif majeur dans des décès imputables à d’autres affections. La prévention efficace, l’identification précoce et la prise en charge adéquate des infections maternelles et néonatales et du sepsis peuvent contribuer à réduire le fardeau des infections. Les objectifs de l’étude mondiale sur le sepsis maternel (GLOSS pour son acronyme en anglais) sont: développer et valider des critères d’identification pour des infection maternelle potentiellement sévère et du sepsis maternel; évaluer la fréquence d’utilisation de pratiques recommandées pour la prévention, l’identification précoce et la prise en charge du sepsis maternel; contribuer à la compréhension de la transmission mère-enfant de l’infection bactérienne; évaluer le niveau de sensibilisation des professionnelles de santé au sujet du sepsis maternel et néonatal; mettre en place un réseau d’établissements de santé pour la mise en place des stratégies d’amélioration de la qualité permettant une meilleure identification et prise en charge du sepsis maternel et du sepsis néonatal précoce. Méthodes: Etude prospective de cohorte avec une phase initiale d’une semaine, dans des établissements de santé situés dans des zones géographiques prédéfinies de pays participants dans les régions OMS de l’Afrique, des Amériques, de la Méditerranée orientale, de l’Europe, de l’Asie du Sud-Est et du Pacifique occidental. Pendant sept jours, toutes les femmes admises ou déjà hospitalisées dans des établissements participants présentant une infection présumée ou confirmée pendant la grossesse et jusqu’au 42e jour après l’avortement ou l’accouchement seront incluses dans l’étude. Les femmes seront suivies jusqu’à leur sortie de l’établissement de santé, leur décès ou leur transfert dans un autre établissement. La période maximale de suivi intra-hospitalier sera de 42 jours. Discussion: GLOSS fournira un ensemble de critères d’action pour l’identification des femmes avec une infection maternelle potentiellement sévère ou sepsis maternel. Cette étude fournira des données sur la fréquence du sepsis maternel et l’adoption d’interventions diagnostiques et thérapeutiques efficaces dans différents établissements et pays. Nous allons également explorer les liens entre les interventions et les issues maternelles et périnatales et d’identifier les domaines d’action prioritaires.

Abstract Background We conducted a process evaluation to assess how the World Health Organization’s (WHO) Strategic Approach to strengthening sexual and reproductive health policies and programs (“the SA”) was used in 15 countries that requested WHO’s technical support in addressing unintended pregnancy and unsafe abortion. The SA is a three-stage planning, policy, and program implementation process. We used the social ecological model (SEM) to analyze the contextual factors that influenced SA implementation. Methods We used a two-phased sequential approach to data collection and analysis. In Phase A, we conducted a document and literature review and synthesized data thematically. In Phase B, we conducted interviews with stakeholders who used the SA in the countries of interest. We used a qualitative method triangulation technique to analyze and combine data from both phases to understand how the SA was implemented in each country. Results Data from 145 documents and 19 interviews described the SA process and activities in each country. All 15 countries completed Stage 1 activities. The activities of Stage 1 determined activities in subsequent stages and varied across countries. Following Stage 1, some countries focused on reforming policies to improve access to sexual and reproductive health (SRH) services whereas others focused on improving provider-level capacity to enhance SRH service quality and improving community-level SRH education. We identified factors across SEM levels that affected SA implementation, including individual- and community-level perceptions of using the SA and the recommendations that emerged from its use, organizational capacity to conduct SA activities, and how well these activities aligned with the existing political climate. Stakeholders perceived SA implementation to be country-driven and systematic in bringing attention to important SRH issues in their countries. Conclusion We identified key success factors for influencing the individual, organization, and system change required for implementing the SA. These include sustaining stakeholder engagement for all SA stages, monitoring and reporting on activities, and leveraging activities and outputs from each SA stage to obtain technical and financial support for subsequent stages. Results may be used to optimize ongoing implementation efforts to improve access to and the quality of SRH services.

An amendment to this paper has been published and can be accessed via the original article.

Abstract Background Information about design, implementation, monitoring and evaluation is central to understand the impact of programmes within the field of sexual, reproductive, maternal, newborn, child and adolescent health (SRMNCAH). Existing reporting guidelines do not orient on reporting of contextual and implementation issues in sufficient detail. We therefore developed Programme Reporting Standards (PRS) to be used by SRMNCAH programme implementers and researchers. Methods Building on the first step of the PRS development (a systematic review to identify reporting items), we conducted a three-round online Delphi consensus survey with experts. Consensus was defined a-priori as 80% agreement of items as essential. This was followed by a technical consultation with a group of experts to refine the items, definitions and their structuring. The revised PRS was piloted to assess its relevance to current SRMNCAH programme reports and identify key issues regarding the use of the PRS. Results Of the 81 participants invited to the Delphi survey, 20 responded to all three rounds. In the final round, 27 items received consensus as essential; three items were ranked as “borderline” essential; 20 items as supplementary. The items were subsequently revised, followed by a technical consultation with 29 experts to further review and refine the PRS. The feedback resulted in substantial changes to the structure and content of the PRS into 24 items across five domains: Programme overview; Programme components and implementation; Monitoring of Implementation; Evaluation and Results; and Synthesis. This version was used in a piloting exercise, where questions regarding how much information to report and how to comment on the quality of the information reported were addressed. All items were kept in the PRS following the pilot although minor changes were made to the flow and description of items. Conclusions The PRS 1.0 is the result of a structured, collaborative process, including methods to incorporate input from SRMNCAH stakeholders. The World Health Organization will develop a document that explains the items in greater detail, and will also apply the PRS to on-going initiatives. We welcome continuous input from the field, while it is being used, to improve its relevance and usefulness.

Abstract Background There is a need for a clear and actionable definition of maternal sepsis, in order to better assess the burden of this condition, trigger timely and effective treatment and allow comparisons across facilities and countries. The objective of this study was to review maternal sepsis definitions and identification criteria and to report on the results of an expert consultation to develop a new international definition of maternal sepsis. Methods All original and review articles and WHO documents, as well as clinical guidelines providing definitions and/or identification criteria of maternal sepsis were included. A multidisciplinary international panel of experts was surveyed through an online consultation in March-April 2016 on their opinion on the existing sepsis definitions, including new definition of sepsis proposed for the adult population (2016 Third International Consensus Definitions for Sepsis and Septic Shock) and importance of different criteria for identification of maternal sepsis. The definition was agreed using an iterative process in an expert face-to-face consensus development meeting convened by WHO and Jhpiego. Results Standardizing the definition of maternal sepsis and aligning it with the current understanding of sepsis in the adult population was considered a mandatory step to improve the assessment of the burden of maternal sepsis by the expert panel. The literature review and expert consultation resulted in a new WHO consensus definition “Maternal sepsis is a life-threatening condition defined as organ dysfunction resulting from infection during pregnancy, child-birth, post-abortion, or post-partum period”. Plans are in progress to validate the new WHO definition of maternal sepsis in a large international population. Conclusion The operationalization of the new maternal sepsis definition requires generation of a set of practical criteria to identify women with sepsis. These criteria should enable clinicians to focus on the timely initiation of actionable elements of care (administration of antimicrobials and fluids, support of vital organ functions, and referral) and improve maternal outcomes.

Background: Many women experience mistreatment during childbirth in health facilities across the world. However, limited evidence exists on how social norms and attitudes of both women and providers influence mistreatment during childbirth. Contextually-specific evidence is needed to understand how normative factors affect how women are treated. This paper explores the acceptability of four scenarios of mistreatment during childbirth. Methods: Two facilities were identified in Abuja, Nigeria. Qualitative methods (in-depth interviews (IDIs) and focus group discussions (FGDs)) were used with a purposive sample of women, midwives, doctors and administrators. Participants were presented with four scenarios of mistreatment during childbirth: slapping, verbal abuse, refusing to help the woman and physical restraint. Thematic analysis was used to synthesize findings, which were interpreted within the study context and an existing typology of mistreatment during childbirth. Results: Eighty-four IDIs and 4 FGDs are included in this analysis. Participants reported witnessing and experiencing mistreatment during childbirth, including slapping, physical restraint to a delivery bed, shouting, intimidation, and threats of physical abuse or poor health outcomes. Some women and providers considered each of the four scenarios as mistreatment. Others viewed these scenarios as appropriate and acceptable measures to gain compliance from the woman and ensure a good outcome for the baby. Women and providers blamed a woman's “disobedience” and “uncooperativeness” during labor for her experience of mistreatment. Conclusions: Blaming women for mistreatment parallels the intimate partner violence literature, demonstrating how traditional practices and low status of women potentiate gender inequality. These findings can be used to facilitate dialogue in Nigeria by engaging stakeholders to discuss how to challenge these norms and hold providers accountable for their actions. Until women and their families are able to freely condemn poor quality care in facilities and providers are held accountable for their actions, there will be little incentive to foster change. Keywords: Maternal health, Childbirth, Mistreatment, Quality of care, Qualitative research, Nigeria

Background: Postpartum haemorrhage (PPH) is the leading cause of maternal mortality worldwide. Prophylactic uterotonic drugs can reduce blood loss and are routinely recommended. There are several uterotonic drugs for preventing PPH, but it is still debatable which drug or combination of drugs is the most effective. Objectives: To identify the most effective and cost-effective uterotonic drug(s) to prevent PPH, and generate a ranking according to their effectiveness and side-effect profile. Methods: The Cochrane Pregnancy and Childbirth’s Trials Register (1 June 2015), ClinicalTrials.gov and the World Health Organization (WHO)’s International Clinical Trials Registry Platform (ICTRP) were searched for unpublished trial reports (30 June 2015). In addition, reference lists of retrieved studies (updated October 2017) were searched for randomised trials evaluating uterotonic drugs for preventing PPH. The study estimated relative effects and rankings for preventing PPH, defined as blood loss of ≥ 500 ml and ≥ 1000 ml. Pairwise meta-analyses and network meta-analysis were performed to determine the relative effects and rankings of all available drugs and combinations thereof [ergometrine, misoprostol (Cytotec®; Pfizer Inc., New York, NY, USA), misoprostol plus oxytocin (Syntocinon®; Novartis International AG, Basel, Switzerland), carbetocin (Pabal®; Ferring Pharmaceuticals, Saint-Prex, Switzerland), ergometrine plus oxytocin (Syntometrine®; Alliance Pharma plc, Chippenham, UK), oxytocin, and a placebo or no treatment]. Primary outcomes were stratified according to the mode of birth, prior risk of PPH, health-care setting, drug dosage, regimen and route of drug administration. Sensitivity analyses were performed according to study quality and funding source, among others. A model-based economic evaluation compared the relative cost-effectiveness separately for vaginal births and caesareans with or without including side effects. Results: From 137 randomised trials and 87,466 women, ergometrine plus oxytocin, carbetocin and misoprostol plus oxytocin were found to reduce the risk of PPH blood loss of ≥ 500 ml compared with the standard drug, oxytocin [ergometrine plus oxytocin: risk ratio (RR) 0.69, 95% confidence interval (CI) 0.57 to 0.83; carbetocin: RR 0.72, 95% CI 0.52 to 1.00; misoprostol plus oxytocin: RR 0.73, 95% CI 0.6 to 0.9]. Each of these three strategies had 100% cumulative probability of being ranked first, second or third most effective. Oxytocin was ranked fourth, with an almost 0% cumulative probability of being ranked in the top three. Similar rankings were noted for the reduction of PPH blood loss of ≥ 1000 ml (ergometrine plus oxytocin: RR 0.77, 95% CI 0.61 to 0.95; carbetocin: RR 0.70, 95% CI 0.38 to 1.28; misoprostol plus oxytocin: RR 0.90, 95% CI 0.72 to 1.14), and most secondary outcomes. Ergometrine plus oxytocin and misoprostol plus oxytocin had the poorest ranking for side effects. Carbetocin had a favourable side-effect profile, which was similar to oxytocin. However, the analysis was restricted to high-quality studies, carbetocin lost its ranking and was comparable to oxytocin. The relative cost-effectiveness of the alternative strategies is inconclusive, and the results are affected by both the uncertainty and inconsistency in the data reported on adverse events. For vaginal delivery, when assuming no adverse events, ergometrine plus oxytocin is less costly and more effective than all strategies except carbetocin. The strategy of carbetocin is both more effective and more costly than all other strategies. When taking adverse events into consideration, all prevention strategies, except oxytocin, are more costly and less effective than carbetocin. For delivery by caesarean section, with and without adverse events, the relative cost-effectiveness is different, again because of the uncertainty in the available data. Limitations: There was considerable uncertainty in findings within the planned subgroup analyses, and subgroup effects cannot be ruled out. Conclusions: Ergometrine plus oxytocin, carbetocin and misoprostol plus oxytocin are more effective uterotonic drug strategies for preventing PPH than the current standard, oxytocin. Ergometrine plus oxytocin and misoprostol plus oxytocin cause significant side effects. Carbetocin has a favourable side-effect profile, which was similar to oxytocin. However, most carbetocin trials are small and of poor quality. There is a need for a large high-quality trial comparing carbetocin with oxytocin; such a trial is currently being conducted by the WHO. The relative cost-effectiveness is inconclusive, and results are affected by uncertainty and inconsistency in adverse events data. Study registration: This study is registered as PROSPERO CRD42015020005; Cochrane Pregnancy and Childbirth Group (substudy) reference number 0871; PROSPERO–Cochrane (substudy) reference number CRD42015026568; and sponsor reference number ERN_13–1414 (University of Birmingham, Birmingham, UK). Funding: Funding for this study was provided by the National Institute for Health Research Health Technology Assessment programme in a research award to the University of Birmingham and supported by the UK charity Ammalife (UK-registered charity 1120236). The funders of the study had no role in study design, data collection, data synthesis, interpretation or writing of the report.

Summary: Background: Preterm birth is the leading cause of death in children younger than 5 years worldwide. Although preterm survival rates have increased in high-income countries, preterm newborns still die because of a lack of adequate newborn care in many low-income and middle-income countries. We estimated global, regional, and national rates of preterm birth in 2014, with trends over time for some selected countries. Methods: We systematically searched for data on preterm birth for 194 WHO Member States from 1990 to 2014 in databases of national civil registration and vital statistics (CRVS). We also searched for population-representative surveys and research studies for countries with no or limited CRVS data. For 38 countries with high-quality data for preterm births in 2014, data are reported directly. For countries with at least three data points between 1990 and 2014, we used a linear mixed regression model to estimate preterm birth rates. We also calculated regional and global estimates of preterm birth for 2014. Findings: We identified 1241 data points across 107 countries. The estimated global preterm birth rate for 2014 was 10·6% (uncertainty interval 9·0–12·0), equating to an estimated 14·84 million (12·65 million–16·73 million) live preterm births in 2014. 12· 0 million (81·1%) of these preterm births occurred in Asia and sub-Saharan Africa. Regional preterm birth rates for 2014 ranged from 13·4% (6·3–30·9) in North Africa to 8·7% (6·3–13·3) in Europe. India, China, Nigeria, Bangladesh, and Indonesia accounted for 57·9 million (41×4%) of 139·9 million livebirths and 6·6 million (44×6%) of preterm births globally in 2014. Of the 38 countries with high-quality data, preterm birth rates have increased since 2000 in 26 countries and decreased in 12 countries. Globally, we estimated that the preterm birth rate was 9×8% (8×3–10×9) in 2000, and 10×6% (9×0–12×0) in 2014. Interpretation: Preterm birth remains a crucial issue in child mortality and improving quality of maternal and newborn care. To better understand the epidemiology of preterm birth, the quality and volume of data needs to be improved, including standardisation of definitions, measurement, and reporting. Funding: WHO and the March of Dimes.

An amendment to this paper has been published and can be accessed via the original article.

Abstract Background Although there are a growing number of initiatives aimed at supporting guideline implementation in resource-constrained settings, few studies assess progress on achieving next steps and goals after the initial activities are completed and the initial funding period has ended. The aim of the current study was to conduct a qualitative process evaluation of progress, barriers, facilitators, and proposed solutions to operationalize nine recommendations to prepare Kosovo to implement the 2012 World Health Organization (WHO) prevention and treatment of postpartum haemorrhage guideline. Methods/Design In 2012, we co-created nine recommendations designed to support implementing the WHO’s guideline on the prevention and treatment of postpartum haemorrhage in Kosovo. The current study uses a realist evaluation approach to assess activities and progress two years after the recommendations were developed. The study involved conducting qualitative focus groups and one-on-one interviews with participants from the first meeting to evaluate the activities and progress on the nine recommendations. Results Forty-three participants provided insights into the barriers and opportunities experienced to date and proposed future directions. Although progress has been made towards implementation of a number of the recommendations, scaling up has been limited by barriers, such as lack of awareness, limited resources, and evaluation challenges. Participants proposed addressing these barriers by building within- and between-country partnerships to facilitate guideline implementation. In addition, participants reported less progress on implementing recommendations related to broader cultural changes, which indicates a need for specific and actionable recommendations to operationalize implementation efforts. Conclusions In the two years since the initial meeting, there has been mixed progress on the recommendations. Based on participant feedback, we refined the recommendations so that they can be operationalized by health care system stakeholders in Kosovo to further support implementation efforts. It is beneficial to share these lessons learned throughout the implementation process to inform next steps in Kosovo and offer ideas for use in other settings.

Abstract Evidence‐informed health care decisions and recommendations need to be made systematically and transparently. Mediating technology can help manage boundaries between groups making decisions and target audiences, enhancing salience, credibility, and legitimacy for all. This article describes the development of the Evidence to Decision (EtD) framework and an interactive tool to create and use frameworks (iEtD) to support communication in decision making. Methods: Using a human‐centered design approach, we created prototypes employing a broad range of methods to iteratively develop EtD framework content and iEtD tool functionality. Results: We developed tailored EtD frameworks for making evidence‐informed decisions and recommendations about clinical practice interventions, diagnostic and screening tests, coverage, and health system and public health options. The iEtD tool provides functionality for preparing frameworks, using them in group discussions, and publishing output for implementation or adaption. EtD and iEtD are intuitive and useful for producers and users of frameworks, and flexible for use across different types of topics, decisions, and organizations. They bring valued structure to panel discussions and transparency to published output. Conclusion: EtD and iEtD can resolve some of the challenges inherent in multicriteria, multistakeholder decision systems. They are freely available online for all to use at https://ietd.epistemonikos.org/ and https://gradepro.org.

BackgroundEscalation 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 findingsThis 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.ConclusionsCervical 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.

Background: High levels of maternal and newborn mortality and morbidity remain a daunting reality in many low-income countries. Several interventions delivered during antenatal care have been shown to improve maternal and newborn outcomes, but stockouts of medical supplies at point of care can prevent implementation of these services. We aimed to evaluate whether a supply chain strategy based on the provision of kits could improve quality of care. Methods: We did a pragmatic, stepped-wedge, cluster-randomised controlled trial at ten antenatal care clinics in Mozambique. Clinics were eligible if they were not already implementing the proposed antenatal care package; they served at least 200 new pregnant women per year; they had Maternal and Child Health (MCH) nurses; and they were willing to participate. All women attending antenatal care visits at the participating clinics were included in the trial. Participating clinics were randomly assigned to shift from control to intervention on prespecified start dates. The intervention involved four components (kits with medical supplies, a cupboard to store these supplies, a tracking sheet to monitor stocks, and a one-day training session). The primary outcomes were the proportion of women screened for anaemia and proteinuria, and the proportion of women who received mebendazole in the first antenatal care visit. The intervention was delivered under routine care conditions, and analyses were done according to the intention-to-treat principle. This trial is registered with the Pan African Clinical Trial Registry, number PACTR201306000550192. Findings: Between March, 2014, and January, 2016, 218 277 antenatal care visits were registered, with 68 598 first and 149 679 follow-up visits. We found significant improvements in all three primary outcomes. In first visits, 5519 (14·6%) of 37 826 women were screened for anaemia in the control period, compared with 30 057 (97·7%) of 30 772 in the intervention period (adjusted odds ratio 832·40; 99% CI 666·81–1039·11; p

INTRODUCTION:Design and provision of good quality maternity care should incorporate what matters to childbearing women. This qualitative systematic review was undertaken to inform WHO intrapartum guidelines. METHODS:Using a pre-determined search strategy, we searched Medline, CINAHL, PsycINFO, AMED, EMBASE, LILACS, AJOL, and reference lists of eligible studies published 1996-August 2016 (updated to January 2018), reporting qualitative data on womens' childbirth beliefs, expectations, and values. Studies including specific interventions or health conditions were excluded. PRISMA guidelines were followed. DATA COLLECTION AND ANALYSIS:Authors' findings were extracted, logged on a study-specific data form, and synthesised using meta-ethnographic techniques. Confidence in the quality, coherence, relevance and adequacy of data underpinning the resulting themes was assessed using GRADE-CERQual. A line of argument synthesis was developed. RESULTS:35 studies (19 countries) were included in the primary search, and 2 in the update. Confidence in most results was moderate to high. What mattered to most women was a positive experience that fulfilled or exceeded their prior personal and socio-cultural beliefs and expectations. This included giving birth to a healthy baby in a clinically and psychologically safe environment with practical and emotional support from birth companions, and competent, reassuring, kind clinical staff. Most wanted a physiological labour and birth, while acknowledging that birth can be unpredictable and frightening, and that they may need to 'go with the flow'. If intervention was needed or wanted, women wanted to retain a sense of personal achievement and control through active decision-making. These values and expectations were mediated through womens' embodied (physical and psychosocial) experience of pregnancy and birth; local familial and sociocultural norms; and encounters with local maternity services and staff. CONCLUSIONS:Most healthy childbearing women want a positive birth experience. Safety and psychosocial wellbeing are equally valued. Maternity care should be designed to fulfil or exceed womens' personal and socio-cultural beliefs and expectations.

[This corrects the article DOI: 10.1371/journal.pone.0194906.].

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

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

BACKGROUND:Caesarean section (CS) rates continue to evoke worldwide concern because of their steady increase, lack of consensus on the appropriate CS rate and the associated additional short- and long-term risks and costs. We present the latest CS rates and trends over the last 24 years. METHODS:We collected nationally-representative data on CS rates between 1990 to 2014 and calculated regional and subregional weighted averages. We conducted a longitudinal analysis calculating differences in CS rates as absolute change and as the average annual rate of increase (AARI). RESULTS:According to the latest data from 150 countries, currently 18.6% of all births occur by CS, ranging from 6% to 27.2% in the least and most developed regions, respectively. Latin America and the Caribbean region has the highest CS rates (40.5%), followed by Northern America (32.3%), Oceania (31.1%), Europe (25%), Asia (19.2%) and Africa (7.3%). Based on the data from 121 countries, the trend analysis showed that between 1990 and 2014, the global average CS rate increased 12.4% (from 6.7% to 19.1%) with an average annual rate of increase of 4.4%. The largest absolute increases occurred in Latin America and the Caribbean (19.4%, from 22.8% to 42.2%), followed by Asia (15.1%, from 4.4% to 19.5%), Oceania (14.1%, from 18.5% to 32.6%), Europe (13.8%, from 11.2% to 25%), Northern America (10%, from 22.3% to 32.3%) and Africa (4.5%, from 2.9% to 7.4%). Asia and Northern America were the regions with the highest and lowest average annual rate of increase (6.4% and 1.6%, respectively). CONCLUSION:The use of CS worldwide has increased to unprecedented levels although the gap between higher- and lower-resource settings remains. The information presented is essential to inform policy and global and regional strategies aimed at optimizing the use of CS.

BACKGROUND:Health systems often fail to use evidence in clinical practice. In maternal and perinatal health, the majority of maternal, fetal and newborn mortality is preventable through implementing effective interventions. To meet this challenge, WHO's Department of Reproductive Health and Research partnered with the Knowledge Translation Program at St. Michael's Hospital (SMH), University of Toronto, Canada to establish a collaboration on knowledge translation (KT) in maternal and perinatal health, called the GREAT Network (Guideline-driven, Research priorities, Evidence synthesis, Application of evidence, and Transfer of knowledge). We applied a systematic approach incorporating evidence and theory to identifying barriers and facilitators to implementation of WHO maternal heath recommendations in four lower-income countries and to identifying implementation strategies to address these. METHODS:We conducted a mixed-methods study in Myanmar, Uganda, Tanzania and Ethiopia. In each country, stakeholder surveys, focus group discussions and prioritization exercises were used, involving multiple groups of health system stakeholders (including administrators, policymakers, NGOs, professional associations, frontline healthcare providers and researchers). RESULTS:Despite differences in guideline priorities and contexts, barriers identified across countries were often similar. Health system level factors, including health workforce shortages, and need for strengthened drug and equipment procurement, distribution and management systems, were consistently highlighted as limiting the capacity of providers to deliver high-quality care. Evidence-based health policies to support implementation, and improve the knowledge and skills of healthcare providers were also identified. Stakeholders identified a range of tailored strategies to address local barriers and leverage facilitators. CONCLUSION:This approach to identifying barriers, facilitators and potential strategies for improving implementation proved feasible in these four lower-income country settings. Further evaluation of the impact of implementing these strategies is needed.

Simon Lewin and colleagues present a methodology for increasing transparency and confidence in qualitative research synthesis.

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

Abstract After publication of the original article [1], it came to the authors’ attention that the Acknowledgements section was not completed correctly. The Acknowledgements of the article should have been as follows.

OBJECTIVE: To review maternal deaths and the dose-related effects of misoprostol on blood loss and pyrexia in randomized trials of misoprostol use for the prevention or treatment of postpartum haemorrhage. METHODS: We searched the Cochrane Controlled Trials Register and Pubmed, without language restrictions, for "(misoprostol AND postpartum) OR (misoprostol AND haemorrhage) OR (misoprostol AND hemorrhage)", and we evaluated reports identified through the Cochrane Pregnancy and Childbirth Group search strategy. Randomized trials comparing misoprostol with either placebo or another uterotonic to prevent or treat postpartum haemorrhage were checked for eligibility. Data were extracted, tabulated and analysed with Reviewer Manager (RevMan) 4.3 software. FINDINGS: We included 46 trials with more than 40 000 participants in the final analysis. Of 11 deaths reported in 5 trials, 8 occurred in women receiving > 600 µg of misoprostol (Peto odds ratio, OR: 2.49; 95% confidence interval, CI: 0.76-8.13). Severe morbidity, defined as the need for major surgery, admission to intensive care, organ failure or body temperature > 40 ºC, was relatively infrequent. In prevention trials, severe morbidity was experienced by 16 of 10 281 women on misoprostol and by 16 of 10 292 women on conventional uterotonics; in treatment trials, it was experienced by 1 of 32 women on misoprostol and by 1 of 32 women on conventional uterotonics. Misoprostol recipients experienced more adverse events than placebo recipients: 8 of 2070 versus 5 of 2032, respectively, in prevention trials, and 5 of 196 versus 2 of 202, respectively, in treatment trials. Meta-analysis of direct and adjusted indirect comparisons of the results of randomized trials showed no evidence that 600 µg are more effective than 400 µg for preventing blood loss > 1000 ml (relative risk, RR: 1.02; 95% CI: 0.71-1.48). Pyrexia was more than twice as common among women who received > 600 µg rather than 400 µg of misoprostol (RR: 2.53; 95% CI: 1.78-3.60). CONCLUSION: Further research is needed to more accurately assess the potential beneficial and harmful effects of misoprostol and to determine the smallest dose that is effective and safe. In this review, 400 µg of misoprostol were found to be safer than > 600 µg and just as effective.

BackgroundDespite growing recognition of neglectful, abusive, and disrespectful treatment of women during childbirth in health facilities, there is no consensus at a global level on how these occurrences are defined and measured. This mixed-methods systematic review aims to synthesize qualitative and quantitative evidence on the mistreatment of women during childbirth in health facilities to inform the development of an evidence-based typology of the phenomenon.Methods and findingsWe searched PubMed, CINAHL, and Embase databases and grey literature using a predetermined search strategy to identify qualitative, quantitative, and mixed-methods studies on the mistreatment of women during childbirth across all geographical and income-level settings. We used a thematic synthesis approach to synthesize the qualitative evidence and assessed the confidence in the qualitative review findings using the CERQual approach. In total, 65 studies were included from 34 countries. Qualitative findings were organized under seven domains: (1) physical abuse, (2) sexual abuse, (3) verbal abuse, (4) stigma and discrimination, (5) failure to meet professional standards of care, (6) poor rapport between women and providers, and (7) health system conditions and constraints. Due to high heterogeneity of the quantitative data, we were unable to conduct a meta-analysis; instead, we present descriptions of study characteristics, outcome measures, and results. Additional themes identified in the quantitative studies are integrated into the typology.ConclusionsThis systematic review presents a comprehensive, evidence-based typology of the mistreatment of women during childbirth in health facilities, and demonstrates that mistreatment can occur at the level of interaction between the woman and provider, as well as through systemic failures at the health facility and health system levels. We propose this typology be adopted to describe the phenomenon and be used to develop measurement tools and inform future research, programs, and interventions.