SARS-CoV-2-Placental effects and association with stillbirth.

SARS-CoV-2 has had a significant impact on pregnancy outcomes due to the effects of the virus and the altered healthcare environment. Stillbirth has been relatively hidden during the COVID-19 pandemic, but a clear link between SARS-CoV-2 and poor fetal outcome emerged in the Alpha and Delta waves. A small minority of women/birthing people who contracted COVID-19 developed SARS-CoV-2 placentitis. In many reported cases this was linked to intrauterine fetal death, although there are cases of delivery just before imminent fetal demise and we shall discuss how some cases are sub-clinical. What is surprising, is that SARS-CoV-2 placentitis is often not associated with severe maternal COVID-19 infection and this makes it difficult to predict. The worst outcomes seem to be with diffuse placental disease which occurs within 21 days of COVID-19 diagnosis. Poor outcomes are often pre-dated by reduced fetal movements but are not associated with ultrasound changes. In some cases, there has also been maternal thrombocytopenia, or coagulation abnormalities, which may provide a clue as to which pregnancies are at risk of fetal demise if a further variant of concern is to emerge. In future, multidisciplinary collaboration and cross-boundary working must be prioritised, to identify quickly such a phenomenon and provide clinicians with clear guidance for reducing fetal death and associated poor outcomes. While we wait to see if COVID-19 brings a future variant of concern, we must focus on appropriate future management of women who have had SARS-CoV-2 placentitis. As a placental condition with an infectious aetiology, SARS-CoV-placentitis is unlikely to recur in a subsequent pregnancy and thus a measured approach to subsequent pregnancy management is needed.

Vaginal birth core information set: study protocol for a Delphi study to achieve a consensus on a 'core information set' for vaginal birth.

INTRODUCTION: Studies have shown that women are often underinformed about potential benefits and risks of vaginal birth. This is in contrast to other modes of birth, such as caesarean birth, for which the risks/benefits are often conveyed prior to undergoing the procedure. A core information set (CIS) is an agreed set of information points that should be discussed with all patients prior to undergoing a procedure or intervention. This CIS could improve the quality of information given regarding mode of birth options, as women will be given information prioritised by patients and stakeholders regarding vaginal birth, empowering them to make informed decisions about their birth. We aim to describe the protocol for the development of this vaginal birth CIS. METHODS AND ANALYSIS: We will develop the CIS by: (1) Compiling a 'long-list' of information points about vaginal birth by: undertaking a scoping review of studies and patient information leaflets; interviews with antenatal/postnatal women, an online survey of stakeholders. (2) Collating the 'long-list' of information points and developing the Delphi survey. Think-aloud interviews will refine the survey. (3) Conducting a two-round Delphi survey. 200 stakeholder participants will be recruited. Items rated critically important by ≥80% of participants in one stakeholder group, or with no consensus, will be carried through to a stakeholder consensus meeting to decide the final CIS. Planned start date is 1 June 2022. Planned end date is 31 August 2023. ETHICS AND DISSEMINATION: This project has been given a favourable ethics opinion by the University of Bristol Research Ethics Committee (Ref: 10530). Approval from the ethics committee will be sought for any protocol amendments, and the principal investigator will be responsible for these changes. Findings will be presented at relevant conferences and published in a high-impact journal. We will disseminate the CIS, via Policy Bristol, to clinical policy and guideline developers.

Interventions to enhance medication adherence in pregnancy- a systematic review.

BACKGROUND: Sub-optimal medication adherence in pregnant women with chronic disease and pregnancy-related indications has the potential to adversely affect maternal and perinatal outcomes. Adherence to appropriate medications is advocated during and when planning pregnancy to reduce risk of adverse perinatal outcomes relating to chronic disease and pregnancy-related indications. We aimed to systematically identify effective interventions to promote medication adherence in women who are pregnant or planning to conceive and impact on perinatal, maternal disease-related and adherence outcomes. METHODS: Six bibliographic databases and two trial registries were searched from inception to 28th April 2022. We included quantitative studies evaluating medication adherence interventions in pregnant women and women planning pregnancy. Two reviewers selected studies and extracted data on study characteristics, outcomes, effectiveness, intervention description (TIDieR) and risk of bias (EPOC). Narrative synthesis was performed due to study population, intervention and outcome heterogeneity. RESULTS: Of 5614 citations, 13 were included. Five were RCTs, and eight non-randomised comparative studies. Participants had asthma (n = 2), HIV (n = 6), inflammatory bowel disease (IBD; n = 2), diabetes (n = 2) and risk of pre-eclampsia (n = 1). Interventions included education +/- counselling, financial incentives, text messaging, action plans, structured discussion and psychosocial support. One RCT found an effect  of the tested intervention on self-reported antiretroviral adherence but not objective adherence. Clinical outcomes were not evaluated. Seven non-randomised comparative studies found an association between the tested intervention and at least one outcome of interest: four found an association between receiving the intervention and both improved clinical or perinatal outcomes and adherence in women with IBD, gestational diabetes mellitus (GDM), and asthma. One study in women with IBD reported an association between receiving the intervention and maternal outcomes but not for self-reported adherence. Two studies measured only adherence outcomes and reported an association between receiving the intervention and self-reported and/or objective adherence in women with HIV and risk of pre-eclampsia. All studies had high or unclear risk of bias. Intervention reporting was adequate for replication in two studies according to the TIDieR checklist. CONCLUSIONS: There is a need for high-quality RCTs reporting replicable interventions to evaluate medication adherence interventions in pregnant women and those planning pregnancy. These should assess both clinical and adherence outcomes.

Interventions, outcomes and outcome measurement instruments in stillbirth care research: A systematic review to inform the development of a core outcome set.

BACKGROUND: A core outcome set could address inconsistent outcome reporting and improve evidence for stillbirth care research, which have been identified as an important research priority. OBJECTIVES: To identify outcomes and outcome measurement instruments reported by studies evaluating interventions after the diagnosis of a stillbirth. SEARCH STRATEGY: Amed, BNI, CINAHL, ClinicalTrials.gov, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Embase, MEDLINE, PsycINFO, and WHO ICTRP from 1998 to August 2021. SELECTION CRITERIA: Randomised and non-randomised comparative or non-comparative studies reporting a stillbirth care intervention. DATA COLLECTION AND ANALYSIS: Interventions, outcomes reported, definitions and outcome measurement tools were extracted. MAIN RESULTS: Forty randomised and 200 non-randomised studies were included. Fifty-eight different interventions were reported, labour and birth care (52 studies), hospital bereavement care (28 studies), clinical investigations (116 studies), care in a multiple pregnancy (2 studies), psychosocial support (28 studies) and care in a subsequent pregnancy (14 studies). A total of 391 unique outcomes were reported and organised into 14 outcome domains: labour and birth; postpartum; delivery of care; investigations; multiple pregnancy; mental health; emotional functioning; grief and bereavement; social functioning; relationship; whole person; subsequent pregnancy; subsequent children and siblings and economic. A total of 242 outcome measurement instruments were used, with 0-22 tools per outcome. CONCLUSIONS: Heterogeneity in outcome reporting, outcome definition and measurement tools in care after stillbirth exists. Considerable research gaps on specific intervention types in stillbirth care were identified. A core outcome set is needed to standardise outcome collection and reporting for stillbirth care research.

Antenatal care in Nepal: a qualitative study into missed opportunities in the first trimester.

BACKGROUND: Use of timely antenatal care has been identified as key to facilitating healthy pregnancies worldwide. Although considerable investment has been made to enhance maternal health services in Nepal, approximately one-third of women do not attend antenatal care until after the first trimester (late). These women miss out on the benefits of screening and interventions that are most effective in the first trimester. OBJECTIVE: This study aimed to identify the missed opportunities of women who do not attend antenatal care in the first trimester, and to explore some of the factors underlying late attendance and consider potential solutions for minimizing these missed opportunities in the future. STUDY DESIGN: This study was conducted in 3 hospitals in Nepal. Focus groups (n=18) with a total of 48 postnatal women and 49 staff members, and 10 individual interviews with stakeholders were conducted. Purposive sampling facilitated the obtainment of a full range of maternity experiences, staff categories, and stakeholder positions. Data were qualitative and analyzed using a thematic approach. RESULTS: Limited awareness among women of the importance of early antenatal care was reported as a key factor behind attendance only after the first trimester. The family and community were described as significant influencers in women's decision-making regarding the timing of antenatal care. The benefits of early ultrasound scanning and effective supplementation in pregnancy were the major missed opportunities. Increasing awareness, reducing cost, and enhancing interprofessional collaboration were suggested as potential methods for improving timely initiation of antenatal care. CONCLUSION: Limited awareness continues to drive late attendance to antenatal care after the first trimester. Investment in services in the first trimester and community health education campaigns are needed to improve this issue and enhance maternal and neonatal outcomes.

Does provision of antenatal care in Southern Asia improve neonatal survival? A systematic review and meta-analysis.

BACKGROUND: Southern Asia has one of the highest burdens of neonatal mortality worldwide (26/1000 live births). Ensuring that women receive antenatal care from a skilled provider may play an important role in reducing this burden. OBJECTIVE: This study aimed to determine whether antenatal care received from a skilled provider could reduce neonatal mortality in Southern Asia by systematically reviewing existing evidence. STUDY DESIGN: Seven databases were searched (MEDLINE, Embase, Cochrane Library, CINAHL, PubMed, PsycINFO, and International Bibliography of the Social Sciences [IBSS]). The key words included: "neonatal mortality," "antenatal care," and "Southern Asia." Nonrandomized comparative studies conducted in Southern Asia reporting on neonatal mortality in women who received antenatal care compared with those who did not were included. Two authors carried out the screening and data extraction. The Risk of Bias Assessment tool for Non-randomized Studies (RoBANS) was used to assess quality of studies. Results were reported using a random-effects model based on odds ratios with 95% confidence intervals. RESULTS: Four studies were included in a meta-analysis of adjusted results. The pooled odds ratio was 0.46 (95% confidence interval, 0.24 to 0.86) for neonatal deaths among women having at least 1 antenatal care visit during pregnancy compared with women having none. In the final meta-analysis, 16 studies could not be included because of lack of adjustment for confounders, highlighting the need for further higher-quality studies to evaluate the true impact. CONCLUSION: This review suggests that in Southern Asia, neonates born to women who received antenatal care have a lower risk of death in the neonatal period compared with neonates born to women who did not receive antenatal care. This should encourage health policy to strengthen antenatal care programs in Southern Asia.

Working lives of maternity healthcare workers in Malawi: an ethnography to identify ways to improve care.

BACKGROUND: Maternal mortality in East Africa is high with a maternal mortality rate of 428 per 100,000 live births. Malawi, whilst comparing favourably to East Africa as a whole, continues to have a high maternal mortality rate (349 per 100,000 live births) despite it being reduced by 53% since 2000. To make further improvements in maternal healthcare, initiatives must be carefully targeted and evaluated to achieve maximum influence. The Malawian Government is committed to improving maternal health; however, to achieve this goal, the quality of care must be high. Furthermore, such a goal requires enough staff with appropriate training. There are not enough midwives in Malawi; therefore, focusing on staff working lives has the potential to improve care and retain staff within the system. OBJECTIVE: This study aimed to identify ways in which working lives of maternity healthcare workers could be enhanced to improve clinical care. STUDY DESIGN: We conducted a 1-year ethnographic study of 3 district-level hospitals in Malawi. Data were collected through observations and discussions with staff and analyzed iteratively. The ethnography focused on the interrelationships among staff as these relationships seemed most important to working lives. The field jottings were transcribed into electronic documents and analyzed using NVivo. The findings were discussed and developed with the research team, participants, and other researchers and healthcare workers in Malawi. To understand the data, we developed a conceptual model, "the social order of the hospital," using Bourdieu's work on political sociology. The social order was composed of the social structure of the hospital (hierarchy), rules of the hospital (how staff in different staff groups behaved), and precedent (following the example of those before them). RESULTS: We used the social order to consider the different core areas that emerged from the data: processes, clinical care, relationships, and context. The Malawian system is underresourced with staff unable to provide high-quality care because of the lack of infrastructure and equipment. However, some processes hinder them on national and local level, for example staff rotations and poorly managed processes for labeling drugs. The staff are aware of the clinical care they should provide; however, they sometimes do not provide such care because they are working with the predefined system and they do not want to disrupt it. Within all of this, there are hierarchical relationships and a desire to move to the next level of the system to ensure a better life with more benefits and less direct clinical work. These elements interact to keep care at its most basic as disruption to the "usual" way of doing things is challenging and creates more work. CONCLUSION: To improve the working lives of the Malawian maternity staff, it is necessary to focus on improving the working culture, relationships, and environment. This may help the next generation of Malawian maternity staff to be happier at work and to better provide respectful, comprehensive, high-quality care to women.

Systematic review and narrative synthesis of the impact of Appreciative Inquiry in healthcare.

BACKGROUND: Appreciative Inquiry is a motivational, organisational change intervention, which can be used to improve the quality and safety of healthcare. It encourages organisations to focus on the positive and investigate the best of 'what is' before thinking of 'what might be', deciding 'what should be' and experiencing 'what can be'. Its effects in healthcare are poorly understood. This review seeks to evaluate whether Appreciative Inquiry can improve healthcare. METHODS: Major electronic databases and grey literature were searched. Two authors identified reports of Appreciative Inquiry in clinical settings by screening study titles, abstracts and full texts. Data extraction, in duplicate, grouped outcomes into an adapted Kirkpatrick model: participant reaction, attitudes, knowledge/skills, behaviour change, organisational change and patient outcomes. RESULTS: We included 33 studies. One randomised controlled trial, 9 controlled observational studies, 4 qualitative studies and 19 non-controlled observational reports. Study quality was generally poor, with most having significant risk of bias. Studies report that Appreciative Inquiry impacts outcomes at all Kirkpatrick levels. Participant reaction was positive in the 16 studies reporting it. Attitudes changed in the seventeen studies that reported them. Knowledge/skills changed in the 14 studies that reported it, although in one it was not universal. Behaviour change occurred in 12 of the 13 studies reporting it. Organisational change occurred in all 23 studies that reported it. Patient outcomes were reported in eight studies, six of which reported positive changes and two of which showed no change. CONCLUSION: There is minimal empirical evidence to support the effectiveness of Appreciative Inquiry in improving healthcare. However, the qualitative and observational evidence suggests that Appreciative Inquiry may have a positive impact on clinical care, leading to improved patient and organisational outcomes. It is, therefore, worthy of consideration when trying to deliver improvements in care. However, high-quality studies are needed to prove its effects. PROSPERO REGISTRATION NUMBER: CRD42015014485.

A systematic review and narrative synthesis of antenatal interventions to improve maternal and neonatal health in Nepal.

BACKGROUND: Maternal and neonatal mortality rates remain high in many economically underdeveloped countries, including Nepal, and good quality antenatal care can reduce adverse pregnancy outcomes. However, identifying how to best improve antenatal care can be challenging. OBJECTIVE: To identify the interventions that have been investigated in the antenatal period in Nepal for maternal or neonatal benefit. We wanted to understand their scale, location, cost, and effectiveness. STUDY DESIGN: Online bibliographic databases (Cochrane Central, MEDLINE, Embase, CINAHL Plus, British Nursing Index, PsycInfo, Allied and Complementary Medicine) and trial registries (ClinicalTrials.gov and the World Health Organization Clinical Trials Registry Platform) were searched from their inception till May 24, 2020. We included all studies reporting any maternal or neonatal outcome after an intervention in the antenatal period. We screened the studies and extracted the data in duplicate. A meta-analysis was not possible because of the heterogeneity of the interventions and outcomes, so we performed a narrative synthesis of the included studies. RESULTS: A total of 25 studies met our inclusion criteria. These studies showed a variety of approaches toward improving antenatal care (eg, educational programs, incentive schemes, micronutrient supplementation) in different settings (home, community, or hospital-based) and with a wide variety of outcomes. Less than a quarter of the studies were randomized controlled trials, and many were single-site or reported only short-term outcomes. All studies reported having made a positive impact on antenatal care in some way, but only 3 provided a cost-benefit analysis to support implementation. None of these studies focused on the most remote communities in Nepal. CONCLUSION: Our systematic review found good quality evidence that micronutrient supplementation and educational interventions can bring important clinical benefits. Iron and folic acid supplementation significantly reduces neonatal mortality and maternal anemia, whereas birth preparedness classes increase the uptake of antenatal and postnatal care, compliance with micronutrient supplementation, and awareness of the danger signs in pregnancy.

Protocol for the development of a core outcome set for stillbirth care research (iCHOOSE Study).

INTRODUCTION: Stillbirth is associated with significant physical, psychosocial and economic consequences for parents, families, wider society and the healthcare system. There is emerging momentum to design and evaluate interventions for care after stillbirth and in subsequent pregnancies. However, there is insufficient evidence to inform clinical practice compounded by inconsistent outcome reporting in research studies. To address this paucity of evidence, we plan to develop a core outcome set for stillbirth care research, through an international consensus process with key stakeholders including parents, healthcare professionals and researchers. METHODS AND ANALYSIS: The development of this core outcome set will be divided into five distinct phases: (1) Identifying potential outcomes from a mixed-methods systematic review and analysis of interviews with parents who have experienced stillbirth; (2) Creating a comprehensive outcome long-list and piloting of a Delphi questionnaire using think-aloud interviews; (3) Choosing the most important outcomes by conducting an international two-round Delphi survey including high-income, middle-income and low-income countries; (4) Deciding the core outcome set by consensus meetings with key stakeholders and (5) Dissemination and promotion of the core outcome set. A parent and public involvement panel and international steering committee has been convened to coproduce every stage of the development of this core outcome set. ETHICS AND DISSEMINATION: Ethical approval for the qualitative interviews has been approved by Berkshire Ethics Committee REC Reference 12/SC/0495. Ethical approval for the think-aloud interviews, Delphi survey and consensus meetings has been awarded from the University of Bristol Faculty of Health Sciences Research Ethics Committee (Reference number: 116535). The dissemination strategy is being developed with the parent and public involvement panel and steering committee. Results will be published in peer-reviewed specialty journals, shared at national and international conferences and promoted through parent organisations and charities. PROSPERO REGISTRATION NUMBER: CRD42018087748.

Maternal Near Miss Analysis in Three Hospitals of Nepal: An Assessment Using Three Delays Model.

BACKGROUND: Maternal Near Miss cases have similarities with those dying from such complications and so present an important opportunity to improve practice. This study was conducted to assess the prevalence of Maternal Near Miss events and identify the delays experienced. METHODS: This was a facility-based cross-sectional study conducted in three tertiary referral hospitals from three provinces of Nepal. All the women surviving a near miss event during six months data collection period were included in the study. RESULTS: There were 67 near miss cases, 7 maternal deaths, and 9158 live births in the study hospitals during the data collection period. This resulted in Maternal Near Miss ratio of 7.31/1000 live births and facility-based Maternal Mortality Ratio of 76/100,000 live births. Severe obstetric haemorrhage (54%) was the most frequent clinical cause of near miss, followed by hypertensive disorders (43%). At least one type of delay was experienced by 85% women. First delay occurred in 63% (42 of 67) cases, second delay occurred in 52% (33 of 62) cases and third delay occurred in 55% (37 of 67) cases. CONCLUSIONS: This study found out that all three delays were common among women experiencing maternal near miss event. Raising awareness regarding dangers signs, improving referral system and strengthening ability of health workers can help in reducing these delays.

Assessing the impact of a motivational intervention to improve the working lives of maternity healthcare workers: a quantitative and qualitative evaluation of a feasibility study in Malawi.

BACKGROUND: Globally too many mothers and babies die during childbirth; 98% of maternal deaths are avoidable. Skilled clinicians can reduce these deaths; however, there is a world-wide shortage of maternity healthcare workers. Malawi has enough to deliver 20% of its maternity care. A motivating work environment is important for healthcare worker retention. To inform a future trial, we aimed to assess the feasibility of implementing a motivational intervention (Appreciative Inquiry) to improve the working lives of maternity healthcare workers and patient satisfaction in Malawi. METHODS: Three government hospitals participated over 1 year. Its effectiveness was assessed through: a monthly longitudinal survey of working life using psychometrically validated instruments (basic psychological needs, job satisfaction and work-related quality of life); a before and after questionnaire of patient satisfaction using a patient satisfaction tool validated in low-income settings with a maximum score of 80; and a qualitative template analysis encompassing ethnographic data, semi-structured interviews and focus groups with staff. RESULTS: The intervention was attended by all 145 eligible staff, who also participated in the longitudinal study. The general trend was an increase in the scores for each scale except for the basic psychological needs score in one site. Only one site demonstrated strong evidence for the intervention working in the work-related quality of life scales. Pre-intervention, 162 postnatal women completed the questionnaire; post-intervention, 191 postnatal women participated. Patient satisfaction rose in all three sites; referral hospital 4.41 rise (95% CI 1.89 to 6.95), district hospital 10.22 (95% CI 7.38 to 13.07) and community hospital 13.02 (95% CI 10.48 to 15.57). The qualitative data revealed that staff felt happier, that their skills (especially communication) had improved, behaviour had changed and systems had developed. CONCLUSIONS: We have shown that it is possible to implement Appreciative Inquiry in government facilities in Malawi, which has the potential to change the way staff work and improve patient satisfaction. The mixed methods approach revealed important findings including the importance of staff relationships. We have identified clear implementation elements that will be important to measure in a future trial such as implementation fidelity and inter-personal relationship factors.

A cross-sectional study to evaluate antenatal care service provision in 3 hospitals in Nepal.

BACKGROUND: Globally, many mothers and their babies die during pregnancy and childbirth. A key element of optimizing outcomes is high-quality antenatal care. The Government of Nepal has significantly improved antenatal care and health outcomes through high-level commitment and investment; however, only 69% of patients attend the 4 recommended antenatal appointments. OBJECTIVE: This study aimed to evaluate the quality and perceptions of antenatal care in Nepal to understand compliance with the Nepalese standards. STUDY DESIGN: This cross-sectional study was conducted at a tertiary referral and private hospital in Kathmandu and a secondary hospital in Makwanpur, Nepal. The study recruited 538 female inpatients on postnatal wards during the 2-week data collection period from May 2019 to June 2019. A review of case notes and verbal survey of women to understand the pregnancy information they received and their satisfaction with antenatal care were performed. We created a summary score of the completeness of antenatal care services received ranging from 0 to 50 (50 indicating complete conformity with standards) and investigated the determinants of attending 4 antenatal care visits and patient satisfaction. RESULTS: The median antenatal care attendance was 4 visits at the secondary and referral hospitals and 8 visits at the private hospital. However, 24% of the patients attended <4 visits. Furthermore, 117 of 538 patients (22%) attended the first-trimester visit, and 65 of 538 patients (12%) attended visits at all points recommended in the standards. More than 90% of the women had blood pressure monitoring, hemoglobin estimation, blood grouping and Rhesus typing, and HIV and syphilis screening. Approximately 50% of the women had urinalysis at every visit (interquartile range, 20-100). Moreover, 509 of 538 patients (95%) reported receiving pregnancy information, but retention was variable: 509 of 538 patients (93%) received some information about danger signs, 290 of 502 patients (58%) remembered headaches, and 491 of 502 patients (98%) remembered fluid leaking. The antenatal care completeness score revealed that the private hospital offered the most complete clinical services (mean, 28.7; standard deviation, 7.1) with the secondary hospital performing worst (mean, 19.1; standard deviation, 7.1). The factors influencing attendance at 4 antenatal care visits in the multivariable model were beginning antenatal care in the first trimester of pregnancy (odds ratio, 2.74; 95% confidence interval, 1.36-5.52) and having a lower level of education (no school: odds ratio, 0.46 [95% confidence interval, 0.23-0.91]; grades 1-5: odds ratio, 0.49 [95% confidence interval, 0.26-0.92]). Overall, 303 of 538 women (56%) were satisfied with their antenatal care. The multivariable analysis revealed that satisfaction was more likely in women attending the private hospital than in women attending the referral hospital (odds ratio, 3.63; 95% confidence interval, 1.68-7.82) and lower in women who felt the antenatal care facilities were not adequate (odds ratio, 0.35; 95% confidence interval, 0.21-0.63) and who wanted longer antenatal appointments (odds ratio, 0.5; 95% confidence interval, 0.33-0.75). CONCLUSION: Few women achieved full compliance with the Nepali antenatal care standards; however, some services were delivered well. To improve, each antenatal contact needs to meet its clinical aims and be respectful. To achieve this communication and counseling training for staff, investment in health promotion and delivery of core services are needed. It is important that these interventions address key issues, such as attendance in the first trimester of pregnancy, improving privacy and optimizing communication around danger signs. However, they must be designed alongside staff and service users and their efficacy tested before widespread investment or implementation.

Implications of non-invasive prenatal testing for identifying and managing high-risk pregnancies.

Non-invasive prenatal testing is regularly used to screen for aneuploidies and Rhesus status of a fetus. Since 1997 when free fetal DNA (ffDNA) in the maternal circulation was first identified, it has been hypothesized that it may be possible to use non-invasive prenatal testing (NIPT) to identify high-risk pregnancies including pre-eclampsia, growth restriction and preterm birth. Since then there has been much interest in this area as a way to identify and understand disease processes. This review presents the current evidence for this approach. For pre-eclampsia the hypothesis is that ffDNA would increase but the evidence for this is heterogenous across studies and trimesters. There is however increasing agreement between studies that by the third trimester ffDNA is more likely to be raised in pre-eclamptic patients than controls. For preterm birth, again, the main hypothesis is that ffDNA should increase. The results are also heterogenous, with some studies finding increased ffDNA prior to preterm birth, and others finding no change. For fetal growth restriction, there are competing theories for reduced and increased ffDNA and some studies suggest that levels are raised and some reduced. There are complexities in interpreting all of this evidence as the studies' designs, patient populations, and especially in the context of growth restriction, the definitions are not clear. Furthermore, authors use different biochemical tests and different units to describe their results, making meta-analysis difficult. All of these issues and conflicting findings lead us to the conclusion that currently there is yet no definitive place in clinical practice for NIPT to support the diagnosis and management of high-risk pregnancies. However, it is vital that this research continues as it could open the door to better understanding of the disease process and novel approaches to management.

The timing and quality of antenatal care received by women attending a primary care centre in Iquitos, Peru: A facility exit survey.

BACKGROUND: Maternal mortality is high in Loreto, Peru, but can be reduced by high quality antenatal care. Indicators for the quality of antenatal care received include the timing (with respect to gestational age) and number of antenatal appointments attended, the delivery of antenatal services and health information, and women's perceptions about their care. This study investigated these indicators amongst women receiving antenatal care in predominantly the San Juan Bautista district of Iquitos, Loreto. This was to identify areas for improvement through comparison with antenatal guidelines published by the Ministry of Health, Peru, and the World Health Organization. METHODS: A total of 134 women were recruited at the Centro de Salud, San Juan-a primary care centre in Iquitos. Information about the delivery of antenatal services and the number of and gestational ages at appointments attended was collected from 121/134 women's hand-held antenatal cards. The delivery of health information and women's perceptions about their antenatal care were investigated through questionnaires (133/134 completed). Descriptive statistics, such as frequencies and valid percentages, were determined. RESULTS: Hand-held antenatal cards revealed that 52.9% of participants began their antenatal care in the first trimester. Compared to national guidelines, 42.1% attended appointments at recommended gestational ages and no women received all recommended antenatal services. Most women received information about identifying complications in pregnancy and health and lifestyle topics. Over 85% of women reported satisfaction with their antenatal care. CONCLUSIONS: Timely antenatal attendance and delivery of services should be encouraged to meet national and global standards. Although all services were not delivered in a combined manner according to national guidelines, individual services were mostly delivered to a high standard and therefore a high proportion of women were satisfied with their antenatal care.

The RESPECT Study for consensus on global bereavement care after stillbirth.

OBJECTIVE: To develop global consensus on a set of evidence-based core principles for bereavement care after stillbirth. METHODS: A modified policy-Delphi methodology was used to consult international stakeholders and healthcare workers with experience in stillbirth between September 2017 and October 2018. Five sequential rounds involved two expert stakeholder meetings and three internet-based surveys, including a global internet-based survey targeted at healthcare workers in a wide range of settings. RESULTS: Initially, 23 expert stakeholders considered 43 evidence-based themes derived from systematic reviews, identifying 10 core principles. The global survey received 236 responses from participants in 26 countries, after which nine principles met a priori criteria for inclusion. The final stakeholder meeting and internet-based survey of all participants confirmed consensus on eight core principles. Highest quality bereavement care should be enabled through training of healthcare staff to reduce stigma and establish respectful care, including acknowledgement and support for grief responses, and provision for physical and psychologic needs. Women and families should be supported to make informed choices, including those concerning their future reproductive health. CONCLUSION: Consensus was established for eight principles for stillbirth bereavement care. Further work should explore implementation and involve the voices of women and families globally.

The effects of interactive training of healthcare providers on the management of life-threatening emergencies in hospital.

BACKGROUND: Preparing healthcare providers to manage relatively rare life-threatening emergency situations effectively is a challenge. Training sessions enable staff to rehearse for these events and are recommended by several reports and guidelines. In this review we have focused on interactive training, this includes any element where the training is not solely didactic but provides opportunity for discussions, rehearsals, or interaction with faculty or technology. It is important to understand the effective methods and essential elements for successful emergency training so that resources can be appropriately targeted to improve outcomes. OBJECTIVES: To assess the effects of interactive training of healthcare providers on the management of life-threatening emergencies in hospital on patient outcomes, clinical care practices, or organisational practices, and to identify essential components of effective interactive emergency training programmes. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL and ERIC and two trials registers up to 11 March 2019. We searched references of included studies, conference proceedings, and contacted study authors. SELECTION CRITERIA: We included randomised trials and cluster-randomised trials comparing interactive training for emergency situations with standard/no training. We defined emergency situations as those in which immediate lifesaving action is required, for example cardiac arrests and major haemorrhage. We included all studies where healthcare workers involved in providing direct clinical care were participants. We excluded studies outside of a hospital setting or where the intervention was not targeted at practicing healthcare workers. We included trials irrespective of publication status, date, and language. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane and Cochrane Effective Practice and Organisation of Care (EPOC) Group. Two review authors independently extracted data and assessed the risk of bias of each included trial. Due to the small number of studies and the heterogeneity in outcome measures, we were unable to perform the planned meta-analysis. We provide a structured synthesis for the following outcomes: survival to hospital discharge, morbidity rate, protocol or guideline adherence, patient outcomes, clinical practice outcomes, and organisation-of-care outcomes. We used the GRADE approach to rate the certainty of the evidence and the strength of recommendations for each outcome. MAIN RESULTS: We included 11 studies that reported on 2000 healthcare providers and over 300,000 patients; one study did not report the number of participants. Seven were cluster randomised trials and four were single centre studies. Four studies focused on obstetric training, three on obstetric and neonatal care, two on neonatal training, one on trauma and one on general resuscitations. The studies were spread across high-, middle- and low-income settings.Interactive training may make little or no difference in survival to hospital discharge for patients requiring resuscitation (1 study; 30 participants; 98 events; low-certainty evidence). We are uncertain if emergency training changes morbidity rate, as the certainty of the evidence is very low (3 studies; 1778 participants; 57,193 patients, when reported). We are uncertain if training alters healthcare providers' adherence to clinical protocols or guidelines, as the certainty of the evidence is very low (3 studies; 156 participants; 558 patients). We are uncertain if there were improvements in patient outcomes following interactive training for emergency situations, as we assessed the evidence as very low-certainty (5 studies, 951 participants; 314,055 patients). We are uncertain if training for emergency situations improves clinical practice outcomes as the certainty of the evidence is very low (4 studies; 1417 participants; 28,676 patients, when reported). Two studies reported organisation-of-care outcomes, we are uncertain if interactive emergency training has any effect on this outcome as the certainty of the evidence is very low (634 participants; 179,400 patient population).We examined prespecified subgroups and found no clear commonalities in effect of multidisciplinary training, location of training, duration of the course, or duration of follow-up. We also examined areas arising from the studies including focus of training, proportion of staff trained, leadership of intervention, and incentive/trigger to participate, and again identified no clear mediating factors. The sources of funding for the studies were governmental, local organisations, or philanthropic donors. AUTHORS' CONCLUSIONS: We are uncertain if there are any benefits of interactive training of healthcare providers on the management of life-threatening emergencies in hospital as the certainty of the evidence is very low. We were unable to identify any factors that may have allowed us to identify an essential element of these interactive training courses.We found a lack of consistent reporting, which contributed to the inability to meta-analyse across specialities. More trials are required to build the evidence base for the optimum way to prepare healthcare providers for rare life-threatening emergency events. These trials need to be conducted with attention to outcomes important to patients, healthcare providers, and policymakers. It is vitally important to develop high-quality studies adequately powered and with attention to minimising the risk of bias.

Uterotonic drugs to prevent postpartum haemorrhage: a network meta-analysis.

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

Postpartum haemorrhage (PPH) is the most common reason why mothers die in childbirth worldwide. Although most healthy women can cope well with blood loss after birth, some do not, and this can pose a serious risk to their health and even life. To reduce blood loss after birth, the routine administration of a drug to contract the uterus (uterotonic) has become standard practice across the world. This research seeks to identify which is the most effective and cost-effective drug. Different drugs have been used for reducing the occurrence of PPH. They include oxytocin, misoprostol, ergometrine, carbetocin, and combinations of these drugs, each with different effectiveness and side effects. The study synthesised the available evidence to compare all of these drugs and combinations thereof. After putting the results of all available comparisons together in a network, a ranking among them was calculated, and provided robust effectiveness and side-effect profiles for each drug and their associated costs. The study included 137 randomised trials, involving a total of 87,466 women. The results suggested that ergometrine plus oxytocin, carbetocin and misoprostol plus oxytocin are the most effective strategies for preventing PPH and are more effective than the currently recommended drug, oxytocin. Each of these three strategies had almost 100% probability of being ranked first, second or third most effective. Oxytocin was ranked fourth with an almost 0% probability of being ranked in the top three. Ergometrine plus oxytocin and misoprostol plus oxytocin were the worst drug combinations for side effects, with carbetocin having the most favourable side-effect profile. Carbetocin could prevent approximately one further event of PPH out of three in comparison with oxytocin. However, existing carbetocin studies were small and of poor quality. There is need for a large high-quality study comparing carbetocin with the current standard treatment of oxytocin for the prevention of PPH. The cost analyses of the alternative drug strategies remain inconclusive.

A Randomized Trial of Prophylactic Antibiotics for Miscarriage Surgery.

BACKGROUND: Surgical intervention is needed in some cases of spontaneous abortion to remove retained products of conception. Antibiotic prophylaxis may reduce the risk of pelvic infection, which is an important complication of this surgery, particularly in low-resource countries. METHODS: We conducted a double-blind, placebo-controlled, randomized trial investigating whether antibiotic prophylaxis before surgery to complete a spontaneous abortion would reduce pelvic infection among women and adolescents in low-resource countries. We randomly assigned patients to a single preoperative dose of 400 mg of oral doxycycline and 400 mg of oral metronidazole or identical placebos. The primary outcome was pelvic infection within 14 days after surgery. Pelvic infection was defined by the presence of two or more of four clinical features (purulent vaginal discharge, pyrexia, uterine tenderness, and leukocytosis) or by the presence of one of these features and the clinically identified need to administer antibiotics. The definition of pelvic infection was changed before the unblinding of the data; the original strict definition was two or more of the clinical features, without reference to the administration of antibiotics. RESULTS: We enrolled 3412 patients in Malawi, Pakistan, Tanzania, and Uganda. A total of 1705 patients were assigned to receive antibiotics and 1707 to receive placebo. The risk of pelvic infection was 4.1% (68 of 1676 pregnancies) in the antibiotics group and 5.3% (90 of 1684 pregnancies) in the placebo group (risk ratio, 0.77; 95% confidence interval [CI], 0.56 to 1.04; P = 0.09). Pelvic infection according to original strict criteria was diagnosed in 1.5% (26 of 1700 pregnancies) and 2.6% (44 of 1704 pregnancies), respectively (risk ratio, 0.60; 95% CI, 0.37 to 0.96). There were no significant between-group differences in adverse events. CONCLUSIONS: Antibiotic prophylaxis before miscarriage surgery did not result in a significantly lower risk of pelvic infection, as defined by pragmatic broad criteria, than placebo. (Funded by the Medical Research Council and others; AIMS Current Controlled Trials number, ISRCTN97143849.).

Uterotonic Drugs for the Prevention of Postpartum Haemorrhage: A Cost-Effectiveness Analysis.

OBJECTIVE: The objective of this study was to estimate the relative cost effectiveness for the full range of uterotonic drugs available for preventing postpartum haemorrhage (PPH). METHODS: A model-based economic evaluation was constructed using effectiveness data from a network meta-analysis, and supplemented by the literature. A UK National Health Service (NHS) perspective was adopted for the analysis, which is based on UK costs from published sources. The primary outcome measure is cost per case of PPH avoided (≥ 500 mL blood loss), with secondary outcome measures of cost per case of severe PPH avoided (≥ 1000 mL) and cost per major outcome (surgery) averted also being analysed. RESULTS: Carbetocin is shown to be the most effective strategy. Excluding adverse events, 'ergometrine plus oxytocin' was shown to be the least costly strategy. The incremental cost-effectiveness ratio for prevention of PPH with carbetocin compared with prevention with 'ergometrine plus oxytocin' was £1889 per case of PPH ≥ 500 mL avoided; £30,013 per case of PPH ≥ 1000 mL avoided; and £1,172,378 per major outcome averted. Including adverse events in the analysis showed oxytocin to be the least costly strategy. The incremental cost-effectiveness ratio for prevention of PPH with carbetocin compared with prevention with oxytocin was £928 per case of PPH ≥ 500 mL avoided; £22,900 per case of PPH ≥ 1000 mL avoided; and £894,514 per major outcome averted. CONCLUSION: The results suggest carbetocin, oxytocin and 'ergometrine plus oxytocin' could all be favourable options for being the most cost-effective strategy for preventing PPH. Carbetocin could be the preferred choice, especially if the price of carbetocin decreased. Mixed findings mean a clear-cut conclusion cannot be made as to which uterotonic is the most cost effective. Future research should focus on collecting more robust evidence on the probability of having adverse events from the uterotonic drugs, and on adapting the model for low- and middle-income countries.