Factors influencing the participation of pregnant and lactating women in clinical trials: A mixed-methods systematic review.

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.

Effectiveness of care bundles for prevention and treatment of postpartum hemorrhage: a systematic review.

OBJECTIVE: Care bundles are a promising approach to reducing postpartum hemorrhage-related morbidity and mortality. We assessed the effectiveness and safety of care bundles for postpartum hemorrhage prevention and/or treatment. DATA SOURCES: We searched MEDLINE, Embase, Cochrane CENTRAL, Maternity and Infant Care Database, and Global Index Medicus (inception to June 9, 2023) and ClinicalTrials.gov and the International Clinical Trials Registry Platform (last 5 years) using a phased search strategy, combining terms for postpartum hemorrhage and care bundles. STUDY ELIGIBILITY CRITERIA: Peer-reviewed studies evaluating postpartum hemorrhage-related care bundles were included. Care bundles were defined as interventions comprising ≥3 components implemented collectively, concurrently, or in rapid succession. Randomized and nonrandomized controlled trials, interrupted time series, and before-after studies (controlled or uncontrolled) were eligible. METHODS: Risk of bias was assessed using RoB 2 (randomized trials) and ROBINS-I (nonrandomized studies). For controlled studies, we reported risk ratios for dichotomous outcomes and mean differences for continuous outcomes, with certainty of evidence determined using GRADE. For uncontrolled studies, we used effect direction tables and summarized results narratively. RESULTS: Twenty-two studies were included for analysis. For prevention-only bundles (2 studies), low-certainty evidence suggests possible benefits in reducing blood loss, duration of hospitalization, and intensive care unit stay, and maternal well-being. For treatment-only bundles (9 studies), high-certainty evidence shows that the E-MOTIVE intervention reduced risks of composite severe morbidity (risk ratio, 0.40; 95% confidence interval, 0.32-0.50) and blood transfusion for bleeding, postpartum hemorrhage, severe postpartum hemorrhage, and mean blood loss. One nonrandomized trial and 7 uncontrolled studies suggest that other postpartum hemorrhage treatment bundles might reduce blood loss and severe postpartum hemorrhage, but this is uncertain. For combined prevention/treatment bundles (11 studies), low-certainty evidence shows that the California Maternal Quality Care Collaborative care bundle may reduce severe maternal morbidity (risk ratio, 0.64; 95% confidence interval, 0.57-0.72). Ten uncontrolled studies variably showed possible benefits, no effects, or harms for other bundle types. Nearly all uncontrolled studies did not use suitable statistical methods for single-group pretest-posttest comparisons and should thus be interpreted with caution. CONCLUSION: The E-MOTIVE intervention improves postpartum hemorrhage-related outcomes among women delivering vaginally, and the California Maternal Quality Care Collaborative bundle may reduce severe maternal morbidity. Other bundle designs warrant further effectiveness research before implementation is contemplated.

Atypical pneumonia testing in transplant recipients.

BACKGROUND: The incidence of atypical pneumonia among immunocompromised patients is not well characterized. Establishing a diagnosis of atypical pneumonia is challenging as positive tests must be carefully interpreted. We aimed to assess the test positivity rate and incidence of atypical pneumonia in transplant recipients. METHODS: A retrospective cohort study was conducted at the Yale New Haven Health System in Connecticut. Adults with solid organ transplant, hematopoietic stem cell transplant (HSCT), or chimeric antigen receptor T-cell, who underwent testing for atypical pathogens of pneumonia (Legionella pneumophilia, Mycoplasma pneumoniae, Chlamydia pneumoniae, and Bordetella pertussis) between January 2016 and August 2022 were included. Positive results were adjudicated in a clinical context using pre-defined criteria. A cost analysis of diagnostic testing was performed. RESULTS: Note that, 1021 unique tests for atypical pathogens of pneumonia were performed among 481 transplant recipients. The testing positivity rate was 0.7% (n = 7). After clinical adjudication, there were three cases of proven Legionella and one case of possible Mycoplasma infection. All cases of legionellosis were in transplant recipients within 1-year post-transplantation with recently augmented immunosuppression and lymphopenia. The possible case of Mycoplasma infection was in an HSCT recipient with augmented immunosuppression. The cost of all tests ordered was $50,797.73. CONCLUSION: The positivity rate of tests for atypical pneumonia was very low in this transplant cohort. An algorithmic approach that targets testing for those with compatible host, clinical, radiographic, and epidemiologic factors, and provides guidance on test selection and test interpretation, may improve the diagnostic yield and lead to substantial cost savings.

How do postnatal care guidelines in Australia compare to international standards? A scoping review and comparative analysis.

BACKGROUND: There is no single national guideline in Australia on the provision of postnatal care, which means there is potential for significant variation in the standard and quality of care. This review aimed to systematically identify, synthesise, and assess the quality of postnatal care guidelines produced for use in Australia. A second aim was to compare postnatal care recommendations in Australian guidelines to the National Institute for Health and Care Excellence's (NICE) and the World Health Organization's (WHO) postnatal care recommendations, to identify gaps and areas of disagreement. We focussed on recommendations regarding postnatal assessment of the woman or newborn, infant feeding, discharge planning, or community-based care. METHODS: A scoping review was undertaken informed by the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for scoping reviews. A database search and a manual search of state and national government health departments, professional associations and research institute websites was performed to identify relevant guidelines and recommendations. Guideline quality was assessed using the AGREE II tool. Guideline recommendations from Australia were mapped to 67 NICE/WHO recommendations. Recommendations that partially agreed, were modified, or in disagreement underwent further analysis. RESULTS: A total of 31 Australian postnatal guidelines were identified and overall, these were of moderate- to high-quality. Of the 67 NICE/WHO recommendations, most agreed with the recommendations contained in Australian guidelines. There were five NICE/WHO recommendations with which corresponding Australian recommendations disagreed. There were 12 NICE/WHO recommendations that were commonly modified within Australia's guidelines. There were three NICE/WHO recommendations that did not appear in any Australian guideline. CONCLUSIONS: Recommendations from postnatal guidelines in Australia have a high level of agreement with corresponding NICE/WHO recommendations. The few disagreements and modifications found in guideline recommendations - both across Australia's guidelines and between Australia's and the NICE/WHO guidelines - are worrying and warrant further examination, as they may result in different standards of care across Australia. Identified gaps in guidance should be prioritised for inclusion in new or updated guidelines where appropriate.

Pregnant and postpartum women's experiences of the indirect impacts of the COVID-19 pandemic in high-income countries: a qualitative evidence synthesis.

BACKGROUND: Pregnant and postpartum women's experiences of the COVID-19 pandemic, as well as the emotional and psychosocial impact of COVID-19 on perinatal health, has been well-documented across high-income countries. Increased anxiety and fear, isolation, as well as a disrupted pregnancy and postnatal period are widely described in many studies. The aim of this study was to explore, describe and synthesise studies that addressed the experiences of pregnant and postpartum women in high-income countries during the first two years of the pandemic. METHODS: A qualitative evidence synthesis of studies relating to women's experiences in high-income countries during the pandemic were included. Two reviewers extracted the data using a thematic synthesis approach and NVivo 20 software. The GRADE-CERQual (Confidence in the Evidence from Reviews of Qualitative research) was used to assess confidence in review findings. RESULTS: Sixty-eight studies were eligible and subjected to a sampling framework to ensure data richness. In total, 36 sampled studies contributed to the development of themes, sub-themes and review findings. There were six over-arching themes: (1) dealing with public health restrictions; (2) navigating changing health policies; (3) adapting to alternative ways of receiving social support; (4) dealing with impacts on their own mental health; (5) managing the new and changing information; and (6) being resilient and optimistic. Seventeen review findings were developed under these themes with high to moderate confidence according to the GRADE-CERQual assessment. CONCLUSIONS: The findings from this synthesis offer different strategies for practice and policy makers to better support women, babies and their families in future emergency responses. These strategies include optimising care delivery, enhancing communication, and supporting social and mental wellbeing.

Likelihood of primary cesarean section following induction of labor in singleton cephalic pregnancies at term, compared with expectant management: An Australian population-based, historical cohort study.

INTRODUCTION: There has been increased use of both induction of labor (IOL) and cesarean section for women with term pregnancies in many high-income countries, and a trend toward birth at earlier gestational ages. Existing evidence regarding the association between IOL and cesarean section for term pregnancies is mixed and conflicting, and little evidence is available on the differential effect at each week of gestation, stratified by parity. MATERIAL AND METHODS: To explore the association between IOL and primary cesarean section for singleton cephalic pregnancies at term, compared with two definitions of expectant management (first: at or beyond the week of gestation at birth following IOL; and secondary: only beyond the week of gestation at birth following IOL), we performed analyses of population-based historical cohort data on women who gave birth in one Australian state (Queensland), between July 1, 2012 and June 30, 2018. Women who gave birth before 37+0 or after 41+6 weeks of gestation, had stillbirths, no-labor, multiple births (twins or triplets), non-cephalic presentation at birth, a previous cesarean section, or missing data on included variables were excluded. Four sub-datasets were created for each week at birth (37-40). Unadjusted relative risk, adjusted relative risk using modified Poisson regression, and their 95% confidence intervals were calculated in each sub-dataset. Analyses were stratified by parity (nulliparas vs. parous women with a previous vaginal birth). Sensitivity analyses were conducted by limiting to women with low-risk pregnancies. RESULTS: A total of 239 094 women were included in the analysis, 36.7% of whom gave birth following IOL. The likelihood of primary cesarean section following IOL in a Queensland population-based cohort was significantly higher at 38 and 39 weeks, compared with expectant management up to 41+6 weeks, for both nulliparas and paras with singleton cephalic pregnancies, regardless of risk status of pregnancy and definition of expectant management. No significant difference was found for nulliparas at 37 and 40 weeks; and for paras at 40 weeks. CONCLUSIONS: Future studies are suggested to investigate further the association between IOL and other maternal and neonatal outcomes at each week of gestation in different maternal populations, before making any recommendation.

Comparison of Levels of Nasal, Salivary, and Plasma Antibody to Severe Acute Respiratory Syndrome Coronavirus 2 During Natural Infection and After Vaccination.

BACKGROUND: Most studies of immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) measure antibody or cellular responses in blood; however, the virus infects mucosal surfaces in the nose and conjunctivae and infectious virus is rarely if ever present in the blood. METHODS: We used luciferase immunoprecipitation assays to measure SARS-CoV-2 antibody levels in the plasma, nose, and saliva of infected persons and vaccine recipients. These assays measure antibody that can precipitate the SAR-CoV-2 spike and nucleocapsid proteins. RESULTS: Levels of plasma anti-spike antibody declined less rapidly than levels of anti-nucleocapsid antibody in infected persons. SARS-CoV-2 anti-spike antibody levels in the nose declined more rapidly than antibody levels in the blood after vaccination of infected persons. Vaccination of previously infected persons boosted anti-spike antibody in plasma more than in the nose or saliva. Nasal and saliva anti-spike antibody levels were significantly correlated with plasma antibody in infected persons who had not been vaccinated and after vaccination of uninfected persons. CONCLUSIONS: Persistently elevated SARS-CoV-2 antibody in plasma may not indicate persistence of antibody at mucosal sites such as the nose. The strong correlation of SARS-CoV-2 antibody in the nose and saliva with that in the blood suggests that mucosal antibodies are derived primarily from transudation from the blood rather than local production. While SARS-CoV-2 vaccine given peripherally boosted mucosal immune responses in infected persons, the increase in antibody titers was higher in plasma than at mucosal sites. Taken together, these observations indicate the need for development of mucosal vaccines to induce potent immune responses at sites where SARS-CoV-2 infection occurs. CLINICAL TRIALS REGISTRATION: NCT01306084.

Antenatal Dexamethasone for Early Preterm Birth in Low-Resource Countries.

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

Self-collection of samples for group B streptococcus testing during pregnancy: a systematic review and meta-analysis.

BACKGROUND: Sample self-collection for reproductive tract infection diagnosis has been found to offer greater convenience, privacy, autonomy, and expanded access to testing in non-pregnant adults. This review aimed to determine whether sample self-collection is as accurate as provider-collection for detection of group B streptococcus colonisation in pregnancy and whether a strategy of self-collection compared to provider-collection might improve maternal and neonatal health outcomes. METHODS: We searched CINAHL Plus, Medline, EMBASE, Maternity and Infant Care Database, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews in June 2022. Eligible studies compared self-collected and provider-collected samples taken from the same participants or participants randomised to either self-collection or provider-collection for reproductive tract infection testing using the same test and testing method in pregnant individuals. We included trials and observational studies. Reviewers assessed risk of bias using the QUADAS-2 checklist and independently extracted data. Sensitivity and specificity for group B streptococcus colonisation of self-collected compared to provider-collected samples were pooled using a bivariate, random-effects, meta-analytic model. This review was registered with PROSPERO (CRD42023396573). RESULTS: The search identified 5909 references, of which eleven diagnostic accuracy group B streptococcus studies were included (n = 3269 participants). No studies assessed the effects of self-collection in pregnancy on health outcomes. All studies had high or unclear risk of bias. Pooled sensitivities of self-collected samples for group B streptococcus detection were 82% (95% CI: 66-91%; I2 = 68.85%) in four trials (n = 1226) and 91% (95% CI: 83-96%; I2 = 37.38%) in seven non-randomised studies (n = 2043). Pooled specificities were 99% (95% CI: 98-99%; I2 = 12.08%) and 97% (95% CI: 94-99%; I2 = 72.50%), respectively. CONCLUSIONS: Self-collected samples for group B streptococcus detection in pregnancy had high specificity compared to provider-collection, but lower sensitivity, particularly for included trials. Studies investigating the effect of self-collection on health outcomes, and further higher quality trials comparing accuracy of self-collection to provider-collection, are required.

Analysis of a maternal health medicines pipeline database 2000-2021: New candidates for the prevention and treatment of fetal growth restriction.

OBJECTIVE: The Accelerating Innovation for Mothers project established a new database of candidate medicines under development between 2000 and 2021 for five pregnancy-related conditions, including fetal growth restriction. The objective was to assess medicines for fetal growth restriction and their potential for clinical use globally. DESIGN: Landscape analysis. SETTING: Global (focus on low- and middle-income countries, LMICs). SAMPLE: Drugs, dietary supplements and biologics under investigation for prevention or treatment of fetal growth restriction. METHODS: A research pipeline database of medicines was created through searching AdisInsight, PubMed and various grant and clinical trial databases. Analysis of clinical and preclinical candidates were descriptive. MAIN OUTCOMES MEASURES: Fetal growth restriction candidates in clinical development were identified and ranked as high, medium or low potential based on prespecified criteria, including efficacy, safety and accessibility. RESULTS: Of the 444 unique candidates in the database across all five pregnancy-related conditions, 63 were for fetal growth restriction. Of these, 31 were in clinical development (phases I, II or III) and 32 were in preclinical development. Three candidates, aspirin, l-arginine and vitamin D, were ranked as having high potential as preventive agents. There were no high-potential candidates for treating fetal growth restriction, although five candidates were ranked as having medium potential: allylestrenol, dalteparin, omega-3 fatty acids, tadalafil, and United Nations International Multiple Micronutrient Antenatal Preparation (UNIMMAP). CONCLUSIONS: l-Arginine, aspirin and vitamin D are promising, high-potential preventative agents for fetal growth restriction. Based on the medicines pipeline, new pharmacological agents for fetal growth restriction are unlikely to emerge in the near future.

The representation of women on Australian clinical practice guideline panels, 2010-2020.

OBJECTIVES: To assess the composition by gender of Australian clinical practice guideline development panels; to explore guideline development-related factors that influence the composition of panels. DESIGN, SETTING, PARTICIPANTS: Survey of clinical guidelines published in Australia during 2010-2020 that observed the 2016 NHMRC Standards for Guidelines, identified (June 2021) in the NHMRC Clinical Practice Guideline Portal or by searching the Guideline International Network guidelines library, the Trip medical database, and PubMed. The gender of contributors to guideline development was inferred from gendered titles (guideline documents) or pronouns (online biographies). MAIN OUTCOME MEASURES: The overall proportion of guideline panel members - the guideline contributors who formally considered evidence and formulated recommendations (ie, guideline panel chairs and members) - who were women. RESULTS: Of 406 eligible guidelines, 335 listed the names of people who contributed to their development (82%). Of 7472 named contributors (including 511 guideline panel chairs [6.8%] and 5039 guideline panel members [67.4%]), 3514 were men (47.0%), 3345 were women (44.8%), and gender could not be determined for 612 (8.2%). A total of 215 guideline panel chairs were women (42.1%), 280 were men (54.8%); 2566 guideline panel members were men (50.9%), 2071 were women (41.1%). The proportion of female guideline panel members was smaller than 40% for 179 guidelines (53%) and larger than 60% for 71 guidelines (21%). The median guideline proportion of female panel members was smaller than 50% for all but two years (2017, 2018). CONCLUSIONS: The representation of women in health leadership roles in Australia does not reflect their level of participation in the health care workforce. In particular, clinical guideline development bodies should develop transparent policies for increasing the participation of women in guideline development panels.

Perceptions and experiences of the prevention, detection, and management of postpartum haemorrhage: a qualitative evidence synthesis.

BACKGROUND: Postpartum haemorrhage (PPH), defined as blood loss of 500 mL or more after childbirth, is the leading cause of maternal mortality worldwide. It is possible to prevent complications of PPH with timely and appropriate detection and management. However, implementing the best methods of PPH prevention, detection and management can be challenging, particularly in low- and middle-income countries. OBJECTIVES: Our overall objective was to explore the perceptions and experiences of women, community members, lay health workers, and skilled healthcare providers who have experience with PPH or with preventing, detecting, and managing PPH, in community or health facility settings. SEARCH METHODS: We searched MEDLINE, CINAHL, Scopus, and grey literature on 13 November 2022 with no language restrictions. We then performed reference checking and forward citation searching of the included studies. SELECTION CRITERIA: We included qualitative studies and mixed-methods studies with an identifiable qualitative component. We included studies that explored perceptions and experiences of PPH prevention, detection, and management among women, community members, traditional birth attendants, healthcare providers, and managers. DATA COLLECTION AND ANALYSIS: We used three-stage maximum variation sampling to ensure diversity in terms of relevance of the study to the review objectives, richness of data, and coverage of critical contextual elements: setting (region, country income level), perspective (type of participant), and topic (prevention, detection, management). We extracted data using a data extraction form designed for this review. We used thematic synthesis to analyse and synthesise the evidence, and we used the GRADE-CERQual (Confidence in the Evidence from Reviews of Qualitative research) approach to assess our confidence in each finding. To identify factors that may influence intervention implementation, we mapped each review finding to the Theoretical Domains Framework (TDF) and the Capability, Motivation, and Opportunity model of Behaviour change (COM-B). We used the Behaviour Change Wheel to explore implications for practice. MAIN RESULTS: We included 67 studies and sampled 43 studies for our analysis. Most were from low- or middle-income countries (33 studies), and most included the perspectives of women and health workers. We downgraded our confidence in several findings from high confidence to moderate, low, or very-low confidence, mainly due to concerns about how the studies were conducted (methodological limitations) or concerns about missing important perspectives from some types of participants or in some settings (relevance). In many communities, bleeding during and after childbirth is considered "normal" and necessary to expel "impurities" and restore and cleanse the woman's body after pregnancy and birth (moderate confidence). In some communities, people have misconceptions about causes of PPH or believe that PPH is caused by supernatural powers or evil spirits that punish women for ignoring or disobeying social rules or for past mistakes (high confidence). For women who give birth at home or in the community, female family members or traditional birth attendants are the first to recognise excess bleeding after birth (high confidence). Family members typically take the decision of whether and when to seek care if PPH is suspected, and these family members are often influenced by trusted traditional birth attendants or community midwives (high confidence). If PPH is identified for women birthing at home or in the community, decision-making about the subsequent referral and care pathway can be multifaceted and complex (high confidence). First responders to PPH are not always skilled or trained healthcare providers (high confidence). In health facilities, midwives may consider it easy to implement visual estimation of blood loss with a kidney dish or under-pad, but difficult to accurately interpret the amount of blood loss (very low confidence). Quantifying (rather than estimating) blood loss may be a complex and contentious change of practice for health workers (low confidence). Women who gave birth in health facilities and experienced PPH described it as painful, embarrassing, and traumatic. Partners or other family members also found the experience stressful. While some women were dissatisfied with their level of involvement in decision-making for PPH management, others felt health workers were best placed to make decisions (moderate confidence). Inconsistent availability of resources (drugs, medical supplies, blood) causes delays in the timely management of PPH (high confidence). There is limited availability of misoprostol in the community owing to stockouts, poor supply systems, and the difficulty of navigating misoprostol procurement for community health workers (moderate confidence). Health workers described working on the maternity ward as stressful and intense due to short staffing, long shifts, and the unpredictability of emergencies. Exhausted and overwhelmed staff may be unable to appropriately monitor all women, particularly when multiple women are giving birth simultaneously or on the floor of the health facility; this could lead to delays in detecting PPH (moderate confidence). Inadequate staffing, high turnover of skilled health workers, and appointment of lower-level cadres of health workers are key challenges to the provision of quality PPH care (high confidence). Through team-based simulation training, health workers of different cadres (doctors, midwives, lay health workers) can develop a shared mental model to help them work quickly, efficiently, and amicably as a team when managing women with PPH (moderate confidence). AUTHORS' CONCLUSIONS: Our findings highlight how improving PPH prevention, detection, and management is underpinned by a complex system of interacting roles and behaviours (community, women, health workers of different types and with different experiences). Multiple individual, sociocultural, and environmental factors influence the decisions and behaviours of women, families, communities, health workers, and managers. It is crucial to consider the broader health and social systems when designing and implementing PPH interventions to change or influence these behaviours. We have developed a set of prompts that may help programme managers, policymakers, researchers, and other key stakeholders to identify and address factors that affect implementation and scale-up of interventions to improve PPH prevention, detection, and management.

Challenges of being a maternity service leader during the COVID-19 pandemic: a descriptive analysis of the journey.

BACKGROUND: In Australia, maternity care services provide care for pregnant and postpartum women and their newborns. The COVID-19 pandemic forced these services to quickly adapt and develop policies and procedures for dealing with transmission in health care facilities, as well as work under public health measures to counter its spread within the community. Despite well-documented responses and adaptations by healthcare systems, no studies have examined the experiences of maternity service leaders through the pandemic. This study aimed to explore the experiences of maternity service leaders, to understand their perspectives on what happened in health services and what was required of a leader during the COVID-19 pandemic in one Australian state. METHODS: A longitudinal qualitative study collected data from 11 maternity care leaders during the pandemic in the state of Victoria. Leaders participated in a series of interviews over the 16-month study period, with a total of 57 interviews conducted. An inductive approach to developing codes allowed for semantic coding of the data, then a thematic analysis was conducted to explore patterned meaning across the dataset. RESULTS: One overarching theme, 'challenges of being a maternity service leader during the pandemic', encompassed participant's experiences. Four sub-themes described the experiences of these leaders: (1) needing to be a rapid decision-maker, (2) needing to adapt and alter services, (3) needing to filter and translate information, and (4) the need to support people. At the beginning of the pandemic, the challenges were most acute with slow guideline development, rapid communications from the government and an urgent need to keep patients and staff safe. Over time, with knowledge and experience, leaders were able to quickly adjust and respond to policy change. CONCLUSION: Maternity service leaders played an important role in preparing and adapting services in accordance with government directives and guidelines while also developing strategies tailored to their own health service requirements. These experiences will be invaluable in designing high quality and responsive systems for maternity care in future crises.

New medicines for spontaneous preterm birth prevention and preterm labour management: landscape analysis of the medicine development pipeline.

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.

Low knowledge of newborn danger signs among pregnant women in Papua New Guinea and implications for health seeking behaviour in early infancy - findings from a longitudinal study.

BACKGROUND: Globally, 2.5 million babies die in the first 28 days of life each year with most of these deaths occurring in low- and middle-income countries. Early recognition of newborn danger signs is important in prompting timely care seeking behaviour. Little is known about women's knowledge of newborn danger signs in Papua New Guinea. This study aims to assess this knowledge gap among a cohort of women in East New Britain Province. METHODS: This study assessed knowledge of newborn danger signs (as defined by the World Health Organization) at three time points from a prospective cohort study of women in East New Britain Province, factors associated with knowledge of danger signs after childbirth were assessed using logistic regression. This study includes quantitative and qualitative interview data from 699 pregnant women enrolled at their first antenatal clinic visit, followed up after childbirth (n = 638) and again at one-month post-partum (n = 599). RESULTS: Knowledge of newborn danger signs was very low. Among the 638 women, only 9.4% knew three newborn danger signs after childbirth and only one knew all four essential danger signs defined by Johns Hopkins University 'Birth Preparedness and Complication Readiness' Index. Higher knowledge scores were associated with higher gravidity, income level, partner involvement in antenatal care, and education. CONCLUSION: Low levels of knowledge of newborn danger signs among pregnant women are a potential obstacle to timely care-seeking in rural Papua New Guinea. Antenatal and postnatal education, and policies that support enhanced education and decision-making powers for women and their families, are urgently needed.

Community perspectives and experiences of quality maternal and newborn care in East New Britain, Papua New Guinea.

BACKGROUND: Quality maternal and newborn care is essential for improving the health of mothers and babies. Low- and middle-income countries, such as Papua New Guinea (PNG), face many barriers to achieving quality care for all. Efforts to improve the quality of maternal and newborn care must involve community in the design, implementation, and evaluation of initiatives to ensure that interventions are appropriate and relevant for the target community. We aimed to describe community members' perspectives and experiences of maternal and newborn care, and their ideas for improvement in one province, East New Britain, in PNG. METHODS: We undertook a qualitative descriptive study in partnership with and alongside five local health facilities, health care workers and community members, using a Partnership Defined Quality Approach. We conducted ten focus group discussions with 68 community members (identified through church, market and other community-based groups) in East New Britain PNG to explore perspectives and experiences of maternal and newborn care, identify enablers and barriers to quality care and interventions to improve care. Discussions were transcribed verbatim. A mixed inductive and deductive analysis was conducted including application of the World Health Organisation (WHO) Quality Maternal and Newborn Care framework. RESULTS: Using the WHO framework, we present the findings in accordance with the five experience of care domains. We found that the community reported multiple challenges in accessing care and facilities were described as under-staffed and under resourced. Community members emphasised the importance of good communication and competent, caring and respectful healthcare workers. Both women and men expressed a strong desire for companionship during labor and birth. Several changes were suggested by the community that could immediately improve the quality of care. CONCLUSIONS: Community perspectives and experiences are critical for informing effective and sustainable interventions to improve the quality of maternal and newborn care and increasing facility-based births in PNG. A greater understanding of the care experience as a key component of quality care is needed and any quality improvement initiatives must include the user experience as a key outcome measure.

Improving the care provided to, and experienced by, women and their families during pregnancy and childbirth is important for improving the health of mothers and babies. Community members should be involved in thinking about appropriate ways to improve care. Papua New Guinea (PNG) is a country in the Pacific which faces multiple challenges to improving care during pregnancy and birth. We aimed to understand what community members think about care provided and experienced during labour and birth in East New Britain, a rural province of PNG. We worked with five health facilities, health workers and community members in East New Britain to develop a qualitative research project. We carried out 10 focus group discussions with community members in East New Britain to understand what the provision and experience of care was like during labour and birth, and ways that it could be improved. We found that community members identified multiple challenges in getting to facilities and many facilities were found to have not enough supplies, equipment, or staff. Community members wanted staff that were good at their work but also caring and respectful. Women wanted to have support people present during labour and birth and many men wanted to be present too. Our results show that it is important to understand what the community thinks about the quality of care during labour and birth and this information is helpful to design effective activities to improve the care provided and experienced.

Implementing the WHO Labour Care Guide to reduce the use of Caesarean section in four hospitals in India: protocol and statistical analysis plan for a pragmatic, stepped-wedge, cluster-randomized pilot trial.

BACKGROUND: The World Health Organization (WHO) Labour Care Guide (LCG) is a paper-based labour monitoring tool designed to facilitate the implementation of WHO's latest guidelines for effective, respectful care during labour and childbirth. Implementing the LCG into routine intrapartum care requires a strategy that improves healthcare provider practices during labour and childbirth. Such a strategy might optimize the use of Caesarean section (CS), along with potential benefits on the use of other obstetric interventions, maternal and perinatal health outcomes, and women's experience of care. However, the effects of a strategy to implement the LCG have not been evaluated in a randomised trial. This study aims to: (1) develop and optimise a strategy for implementing the LCG (formative phase); and (2) To evaluate the implementation of the LCG strategy compared with usual care (trial phase). METHODS: In the formative phase, we will co-design the LCG strategy with key stakeholders informed by facility assessments and provider surveys, which will be field tested in one hospital. The LCG strategy includes a LCG training program, ongoing supportive supervision from senior clinical staff, and audit and feedback using the Robson Classification. We will then conduct a stepped-wedge, cluster-randomized pilot trial in four public hospitals in India, to evaluate the effect of the LCG strategy intervention compared to usual care (simplified WHO partograph). The primary outcome is the CS rate in nulliparous women with singleton, term, cephalic pregnancies in spontaneous labour (Robson Group 1). Secondary outcomes include clinical and process of care outcomes, as well as women's experience of care outcomes. We will also conduct a process evaluation during the trial, using standardized facility assessments, in-depth interviews and surveys with providers, audits of completed LCGs, labour ward observations and document reviews. An economic evaluation will consider implementation costs and cost-effectiveness. DISCUSSION: Findings of this trial will guide clinicians, administrators and policymakers on how to effectively implement the LCG, and what (if any) effects the LCG strategy has on process of care, health and experience outcomes. The trial findings will inform the rollout of LCG internationally. TRIAL REGISTRATION: CTRI/2021/01/030695 (Protocol version 1.4, 25 April 2022).

The new WHO Labour Care Guide (LCG) is an innovative partograph that emphasises women-centred, evidence-based care during labour and childbirth. Together with clinicians working at four hospitals in India, we will develop and test a strategy to implement the LCG into routine care in labour wards of these hospitals. We will use a randomised trial design where this LCG strategy is introduced sequentially in each of the four hospitals, in a random order. We will collect data on all women giving birth and their newborns during this period and analyse whether the LCG strategy has any effects on the use of Caesarean section, women's and newborn's health outcomes, and women's experiences during labour and childbirth. While the trial is being conducted, we will also collect qualitative and quantitative data from doctors, nurses and midwives working in these hospitals, to understand their perspectives and experiences of using the LCG in their day-to-day work. In addition, we will collect economic data to understand how much the LCG strategy costs, and how much money it might save if it is effective. Through this study, our international collaboration will generate critical evidence and innovative tools to support implementation of the LCG in other countries.

Factors influencing appropriate use of interventions for management of women experiencing preterm birth: A mixed-methods systematic review and narrative synthesis.

BACKGROUND: Preterm birth-related complications are the leading cause of death in newborns and children under 5. Health outcomes of preterm newborns can be improved with appropriate use of antenatal corticosteroids (ACSs) to promote fetal lung maturity, tocolytics to delay birth, magnesium sulphate for fetal neuroprotection, and antibiotics for preterm prelabour rupture of membranes. However, there are wide disparities in the rate and consistency in the use of these interventions across settings, which may underlie the differential health outcomes among preterm newborns. We aimed to assess factors (barriers and facilitators) affecting the appropriate use of ACS, tocolytics, magnesium sulphate, and antibiotics to improve preterm birth management. METHODS AND FINDINGS: We conducted a mixed-methods systematic review including primary qualitative, quantitative, and mixed-methods studies. We searched MEDLINE, EMBASE, CINAHL, Global Health, and grey literature from inception to 16 May 2022. Eligible studies explored perspectives of women, partners, or community members who experienced preterm birth or were at risk of preterm birth and/or received any of the 4 interventions, health workers providing maternity and newborn care, and other stakeholders involved in maternal care (e.g., facility managers, policymakers). We used an iterative narrative synthesis approach to analysis, assessed methodological limitations using the Mixed Methods Appraisal Tool, and assessed confidence in each qualitative review finding using the GRADE-CERQual approach. Behaviour change models (Theoretical Domains Framework; Capability, Opportunity, and Motivation (COM-B)) were used to map barriers and facilitators affecting appropriate use of these interventions. We included 46 studies from 32 countries, describing factors affecting use of ACS (32/46 studies), tocolytics (13/46 studies), magnesium sulphate (9/46 studies), and antibiotics (5/46 studies). We identified a range of barriers influencing appropriate use of the 4 interventions globally, which include the following: inaccurate gestational age assessment, inconsistent guidelines, varied knowledge, perceived risks and benefits, perceived uncertainties and constraints in administration, confusion around prescribing and administering authority, and inadequate stock, human resources, and labour and newborn care. Women reported hesitancy in accepting interventions, as they typically learned about them during emergencies. Most included studies were from high-income countries (37/46 studies), which may affect the transferability of these findings to low- or middle-income settings. CONCLUSIONS: In this study, we identified critical factors affecting implementation of 4 interventions to improve preterm birth management globally. Policymakers and implementers can consider these barriers and facilitators when formulating policies and planning implementation or scale-up of these interventions. Study findings can inform clinical preterm birth guidelines and implementation to ensure that barriers are addressed, and enablers are reinforced to ensure these interventions are widely available and appropriately used globally.

Correction: Factors influencing appropriate use of interventions for management of women experiencing preterm birth: A mixed-methods systematic review and narrative synthesis.

[This corrects the article DOI: 10.1371/journal.pmed.1004074.].

Prevention and control of non-communicable diseases in antenatal, intrapartum, and postnatal care: a systematic scoping review of clinical practice guidelines since 2011.

BACKGROUND: Non-communicable diseases (NCDs) are a leading cause of maternal mortality and morbidity worldwide. The World Health Organization is developing new recommendations focusing on the management of NCDs for pregnant, intrapartum, and postnatal women. Thus, to support the development of new guidelines and recommendations, we aimed to determine the availability, focus, and scope of recommendations of current guidelines for the management of NCDs during pregnancy, intrapartum, and postnatal period. METHODS: PubMed, Global Index Medicus, TRIP, and Guideline International Network databases were searched on 31 May 2021, to identify any NCD-related guidelines published between 2011 and 2021 with no language or country restrictions. Websites of 165 professional organizations were also searched. Characteristics of included guidelines were analyzed, and recommendations were extracted from guidelines of five high-priority NCD conditions (diabetes, chronic hypertension, respiratory conditions, hemoglobinopathies and sickle cell disease, and mental and substance use disorders). RESULTS: From 6026 citations and 165 websites, 405 guidelines were included of which 132 (33%) were pregnancy-specific and 285 (88%) were developed in high-income countries. Among pregnancy-specific guidelines, the most common conditions for which recommendations were provided were gestational diabetes, circulatory diseases, thyroid disorders, and hypertensive disorders of pregnancy. For the five high-priority conditions, 47 guidelines were identified which provided 1834 recommendations, largely focused on antenatal care interventions (62%) such as early detection, screening tools, pharmacological treatment, and lifestyle education. Postnatal recommendations largely covered postnatal clinical assessments, lifestyle education, and breastfeeding. Health system recommendations largely covered multidisciplinary care teams and strengthening referral pathways. CONCLUSIONS: This study provides a robust assessment of currently available guidelines and mapping of recommendations on NCD management within maternal health services, which will inform the scope of the World Health Organization's future guideline development activities. This study identified a need to develop guidelines that consider NCDs holistically, with an integrated approach to antenatal, intrapartum, and postnatal care, and that are relevant for resource-limited contexts. Any such guidelines should consider what interventions are most essential to improving outcomes for women with NCDs and their newborns, and how variations in quality of NCD-related care can be addressed.