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Background Poor 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 findings We 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. Conclusions This 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., Author(s): Mridula Shankar 1,*, Alya Hazfiarini 1, Rana Islamiah Zahroh 1, Joshua P. Vogel 2, Annie R. A. McDougall 2, Patrick Condron 3, Shivaprasad S. Goudar 4, Yeshita V. Pujar [...]

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.

ObjectiveTo systematically develop evidence-based bundles for care of postpartum hemorrhage (PPH).MethodsAn international technical consultation was conducted in 2017 to develop draft bundles of clinical interventions for PPH taken from the WHO's 2012 and 2017 PPH recommendations and based on the validated "GRADE Evidence-to-Decision" framework. Twenty-three global maternal-health experts participated in the development process, which was informed by a systematic literature search on bundle definitions, designs, and implementation experiences. Over a 6-month period, the expert panel met online and via teleconferences, culminating in a 2-day in-person meeting.ResultsThe consultation led to the definition of two care bundles for facility implementation. The "first response to PPH bundle" comprises uterotonics, isotonic crystalloids, tranexamic acid, and uterine massage. The "response to refractory PPH bundle" comprises compressive measures (aortic or bimanual uterine compression), the non-pneumatic antishock garment, and intrauterine balloon tamponade (IBT). Advocacy, training, teamwork, communication, and use of best clinical practices were defined as PPH bundle supporting elements.ConclusionFor the first response bundle, further research should assess its feasibility, acceptability, and effectiveness; and identify optimal implementation strategies. For the response to refractory bundle, further research should address pending controversies, including the operational definition of refractory PPH and effectiveness of IBT devices.

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.

Aim: To develop evidence‐based clinical algorithms for the assessment and management of spontaneous, uncomplicated labour and vaginal birth. Population: Pregnant women at any stage of labour, with singleton, term pregnancies considered to be at low risk of developing complications. Setting: Health facilities in low‐ and middle‐income countries. Search Strategy: We searched for relevant published algorithms, guidelines, systematic reviews and primary research studies on Cochrane Library, PubMed, and Google on terms related to spontaneous, uncomplicated labour and childbirth up to 01 June 2023. Case scenarios: Three case scenarios were developed to cover assessments and management for spontaneous, uncomplicated first, second and third stage of labour. The algorithms provide pathways for definition, assessments, diagnosis, and links to other algorithms in this series for management of complications. Conclusions: We have developed three clinical algorithms to support evidence‐based decision making during spontaneous, uncomplicated labour and vaginal birth. These algorithms may help guide health care staff to institute respectful care, appropriate interventions where needed, and potentially reduce the unnecessary use of interventions during labour and childbirth. Evidence‐based clinical algorithms may help support respectful, high quality intrapartum care. [Correction added on 23 August 2024, after first online publication: The Abstract has been updated to structure layout in this version.] [ABSTRACT FROM AUTHOR]

Aim: To develop evidence‐based clinical algorithms for management of common intrapartum urinary abnormalities. Population: Women with singleton, term pregnancies in active labour and immediate postnatal period, at low risk of complications. Setting: Healthcare facilities in low‐ and middle‐income countries. Search strategy: A systematic search and review were conducted on the current guidelines from WHO, NICE, ACOG and RCOG. Additional search was done on PubMed and The Cochrane Database of Systematic Reviews up to May 2020. Case scenarios: Four common intrapartum urinary abnormalities were selected: proteinuria, ketonuria, glycosuria and oliguria. Using reagent strip testing, glycosuria was defined as ≥2+ on one occasion or of ≥1+ on two or more occasions. Proteinuria was defined as ≥2+ and presence of ketone indicated ketonuria. Oliguria was defined as hourly urine output ≤30 ml. Thorough initial assessment using history, physical examination and basic investigations helped differentiate most of the underlying causes, which include diabetes mellitus, dehydration, sepsis, pre‐eclampsia, shock, anaemia, obstructed labour, underlying cardiac or renal problems. A clinical algorithm was developed for each urinary abnormality to facilitate intrapartum management and referral of complicated cases for specialised care. Conclusions: Four simple, user‐friendly and evidence‐based clinical algorithms were developed to enhance intrapartum care of commonly encountered maternal urine abnormalities. These algorithms may be used to support healthcare professionals in clinical decision‐making when handling normal and potentially complicated labour, especially in low resource countries. Evidence‐based clinical algorithms developed to guide intrapartum management of commonly encountered urinary abnormalities. An evidence‐based clinical algorithm was developed to enhance intrapartum management of commonly encountered urinary abnormalities. [ABSTRACT FROM AUTHOR]

Aim: The development of an evidence‐based algorithm for the clinical management of deviations in maternal temperature during labour and childbirth. Population: Pregnant women at any stage of labour, with singleton, term (37–42 weeks) pregnancies at low risk of developing complications. Setting: Health facilities in low‐ and middle‐income countries. Search strategy: We searched for international guidelines and prioritised WHO guidelines. In addition, we searched for other sources of evidence in the Cochrane Database of Systematic Reviews, EMBASE, MEDLINE and CINAHL until June 2020. Studies were prioritised according to the hierarchy of evidence. Case scenarios: Two case scenarios were identified: maternal hyperthermia and hypothermia. We developed a single algorithm including both, due to commonalities in diagnosis, monitoring and management of underlying causes. The underlying conditions covered in the pathway include maternal sepsis and infection, chorioamnionitis, pyelonephritis, lower urinary tract and respiratory infections. Key decision points in the algorithm are suspicion of condition, definition, differential diagnosis, monitoring and management. Conclusions: We present an evidence‐based algorithm to assist healthcare professionals in making decisions about appropriate clinical management of deviations in maternal temperature. Research is needed to assess the views of healthcare professionals and women accessing healthcare on the feasibility of implementing the algorithm. An evidence‐based intrapartum care algorithm to support management of deviations in maternal temperature in labour and childbirth. #sepsis #maternitycare. An evidence‐based intrapartum care algorithm to support management of deviations in maternal temperature in labour and childbirth. #sepsis #maternitycare. [ABSTRACT FROM AUTHOR]

Aims: To develop algorithms for identifying, managing and monitoring postpartum haemorrhage (PPH) and other third stage of labour abnormalities after vaginal delivery. Population: Women with low‐risk singleton term pregnancies who have had a vaginal delivery. Setting: Hospital settings with a particular focus on healthcare facilities in low‐ and middle‐income countries (LMICs). Search strategy: Searches for international and national guidance documents, research databases (Cochrane, Medline and CINAHL) and published systematic reviews. Searches were limited to work published in English between 1 January 2008 and 31 December 2018. Case scenarios: Four interlinked case scenarios were identified for algorithm development: (1) an approach to PPH after vaginal delivery, (2) uterine atony, (3) genital tract trauma and (4) retained placenta/placental products. Conclusions: The development of clear approaches to the assessment, resuscitation, treatment and monitoring of the four case scenarios are presented as algorithms, based on available evidence. They need to be field tested and evaluated for effectiveness, and may be adapted for electronic decision support tools using artificial intelligence in different settings. Further research is needed around multimodal sequential packages of care for PPH, conservative surgical measures, resuscitation in LMICs, and how a respectful maternity care focus can be incorporated into the algorithms. Algorithm development for standardised approaches to managing PPH in low‐resource settings. Algorithm development for standardised approaches to managing PPH in low‐resource settings. [ABSTRACT FROM AUTHOR]

Aim: To construct evidence‐based algorithms for the assessment and management of common amniotic fluid abnormalities detected during labour. Population: Low‐risk singleton, term pregnant women in labour. Setting: Birth facilities in low‐ and middle‐income countries. Search Strategy: We searched international guidelines published by the American College of Obstetricians and Gynecologists (ACOG), the National Institute for Health and Care Excellence (NICE), the Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG), the Royal College of Obstetricians and Gynaecologists (RCOG), the Society of Obstetrics and Gynaecology (SOGC) and the World Health Organization (WHO). We also searched The Cochrane Library and MEDLINE up to 20 January 2020 using keywords for relevant systematic reviews and randomised trials. Case scenarios: We developed evidence‐based intrapartum care algorithms for four case scenarios: oligohydramnios; meconium‐stained amniotic fluid; bloody amniotic fluid or vaginal bleeding; and purulent amniotic fluid or discharge. These conditions may be associated with fetal and /or maternal morbidity. Differential diagnosis includes uteroplacental insufficiency, fetal growth restriction, fetal distress, abruption, placenta or vasa praevia, uterine rupture and intra‐amniotic infection, respectively. Algorithms include how to assess for, diagnose and manage these conditions. Conclusions: Four algorithms are presented, to provide a systematic approach and guidance on the clinical management for the following amniotic fluid abnormalities: oligohydramnios; meconium‐stained liquor; bloody amniotic fluid or vaginal bleeding; and purulent amniotic fluid or discharge. These algorithms may be beneficial in supporting clinical decision making, particularly in low‐resource settings. Evidence based algorithms for management of common amniotic fluid abnormalities seen during labour. Evidence based algorithms for management of common amniotic fluid abnormalities seen during labour. [ABSTRACT FROM AUTHOR]

Aim: To develop algorithms as decision support tools for identifying, managing and monitoring abnormal uterine activity during labour. Population: Women with singleton, term (37–42 weeks) pregnancies in active labour at admission. Setting: Institutional birth settings in low‐ and middle‐income countries (the algorithm may be applicable to any health facility). Search strategy: PubMed was searched up to January 2020 using keywords. We also searched The Cochrane Library, and international guidelines from World Health Organization (WHO), National Institute for Health and Care Excellence (NICE), American College of Obstetricians and Gynecologists (ACOG) and French College of Gynaecologists and Obstetricians (CNGOF). Case scenarios: Algorithms were developed for two case scenarios: uterine hypoactivity and excessive uterine contractions. Key themes in the algorithm are: diagnosis, identification of probable causes, assessment of maternal and fetal condition and labour progress, monitoring and management. Conclusion: The algorithms for uterine hypoactivity and excessive uterine contractions have been developed to facilitate safe and effective management of abnormal uterine activity during labour. Research is needed to assess the views of healthcare professionals and women accessing healthcare to explore the feasibility of implementing these algorithms, and impact on labour outcomes. An evidence‐based algorithm to support clinical management of abnormal uterine activity during labour. An evidence‐based algorithm to support clinical management of abnormal uterine activity during labour. [ABSTRACT FROM AUTHOR]

Objective: To construct algorithms with a sequential decision analysis pathway for monitoring of the fetal heart rate and managing fetal heart rate bradycardia, late decelerations and tachycardia during labour. Population: Low‐risk pregnant women in labour with singleton cephalic term pregnancies. Setting: Institutional births in low‐ and middle‐income countries. Search strategy: We sought relevant published clinical algorithms, guidelines and randomised trials/reviews by searching the Cochrane Library, PubMed and Google on the terms: "fetal AND heart AND rate AND algorithm AND (labour OR intrapartum)", up to March 2020. Case scenarios: The two scenarios included were fetal heart rate bradycardia or late decelerations (potentially related to uterine rupture, placental abruption, cord prolapse, maternal hypotension, uterine hyperstimulation or unexplained) and fetal heart rate tachycardia (potentially related to maternal hyperthermia, infection, dehydration or unexplained). The algorithms provide pathways for definition, assessment, diagnosis, interventions to correct the abnormalities and ongoing monitoring leading to mode of birth, and linking to other algorithms in the series. Conclusions: The algorithms provide a framework for monitoring and managing fetal heart rate bradycardia, late decelerations and tachycardia during labour. We emphasise the inherent diagnostic inaccuracy of fetal heart rate monitoring, the tendency to over‐diagnose fetal compromise, the need to consider fetal heart rate information in the context of other clinical features and the need to engage in informed, shared, family‐centred decision‐making. We note the need for further research on methods of fetal assessment during labour including clinical fetal arousal testing and the rapid biophysical profile test. Decision analysis algorithms for fetal bradycardia, late decelerations and tachycardia highlight diagnostic limitations. Decision analysis algorithms for fetal bradycardia, late decelerations and tachycardia highlight diagnostic limitations. [ABSTRACT FROM AUTHOR]

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.

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.