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Context.--Chronic histiocytic intervillositis (CHI) is a rare condition characterized by maternal immune cell infiltration into the human placenta. CHI is strongly associated with fetal growth restriction, miscarriage, and stillbirth, and knowledge of its etiology, and consequently effective treatment, is limited. Currently, diagnosis is largely subjective and varies between centers, making comparison between studies challenging. Objective.--To objectively quantify and interrelate inflammatory cells and fibrin in placentas with CHI compared with controls and determine how pathology may be altered in subsequent pregnancies following diagnosis. Macrophage phenotype was also investigated in untreated cases of CHI. Design.--Computerized analysis was applied to immunohistochemically stained untreated (index) cases of CHI, subsequent pregnancies, and controls. Index placentas were additionally stained by immunofluorescence for M1 (CD80 and CD86) and M2 macrophage markers (CD163 and CD206). Results.--Quantification revealed a median 32-fold increase in macrophage infiltration in index cases versus controls, with CHI recurring in 2 of 11 (18.2%) subsequent pregnancies. A total of 4 of 14 placentas (28.6%) with a diagnosis of CHI did not exhibit infiltration above controls. Macrophages in index pregnancies strongly expressed CD163. There was no significant difference in fibrin deposition between index cases and controls, although subsequent pregnancies displayed a 2-fold decrease compared with index pregnancies. [CD3.sup.+] T cells were significantly elevated in index pregnancies; however, they returned to normal levels in subsequent pregnancies. Conclusions.--In CHI, intervillous macrophages expressed CD163, possibly representing an attempt to resolve inflammation. Computerized analysis of inflammation in CHI may be useful in determining how treatment affects recurrence, and alongside pathologist expertise in grading lesion severity. doi: 10.5858/arpa.2022-0494-OA, Chronic histiocytic intervillositis (CHI) is an inflammatory lesion of the human placenta affecting 6 in every 10 000 pregnancies past 12 weeks' gestation, (1) wherein maternal macrophages infiltrate the intervillous [...]

Abstract Chronic histiocytic intervillositis (CHI) is a recurrent placental lesion where maternal macrophages infiltrate the intervillous space. Its cause is unknown, though due to similarities to rejected allografts one hypothesis is that CHI represents maternal–fetal rejection. Here, virtual crossmatching was applied to healthy pregnancies and those with a history of CHI. Anti-HLA antibodies, measured by Luminex, were present in slightly more controls than CHI (8/17 (47.1%) vs 5/14 (35.7%)), but there was no significant difference in levels of sensitisation or fetal specific antibodies. Quantification of immunohistochemical staining for HLA-Class II was increased in syncytiotrophoblast of placentas with CHI (Grade 0.44 [IQR 0.1–0.7]) compared to healthy controls (0.06 [IQR 0–0.2]) and subsequent pregnancies (0.13 [IQR 0–0.3]) (P = 0.0004). HLA-Class II expression was positively related both to the severity of CHI (r = 0.67) and C4d deposition (r = 0.48). There was no difference in overall C4d and HLA-Class I immunostaining. Though increased anti-HLA antibodies were not evident in CHI, increased expression of HLA-Class II at the maternal–fetal interface suggests that they may be relevant in its pathogenesis. Further investigation of antibodies immediately after diagnosis is warranted in a larger cohort of CHI cases to better understand the role of HLA in its pathophysiology.

Abstract Background Women experiencing pregnancy after stillbirth experience high levels of anxiety, fear and depression. Standard antenatal care may be emotionally unsuitable for many women at this time, and there is a lack of evidence on what interventions or approaches to care might benefit these women. Therapeutic massage may assist women after stillbirth by decreasing anxiety, worry and stress. Objective This paper outlines the objectives, methodology, outcome and assessment measures for the Helping suppOrt individuals Pregnant after Experiencing a Stillbirth (HOPES) feasibility trial which evaluates massage as an adjunct approach to care for pregnant women who have experienced a prior stillbirth. It also outlines data collection timing and considerations for analysing the data. Methods HOPES will use a convergent parallel mixed-methods, single-arm repeated measures trial design in trained massage therapists’ private clinics across Australia. HOPES aims to recruit 75 individuals pregnant after a previous stillbirth. The intervention is massage therapy treatments, and participants will receive up to five massages within a 4-month period at intervals of their choosing. Primary quantitative outcomes are the feasibility and acceptability of the massage intervention. Secondary outcomes include determining the optimal timing of massage therapy delivery and the collection of measures for anxiety, worry, stress and self-management. A thematic analysis of women’s experiences undertaking the intervention will also be conducted. A narrative and joint display approach to integrate mixed-methods data is planned. Discussion The HOPES study will determine the feasibility and preliminary evidence for massage therapy as an intervention to support women who are pregnant after a stillbirth. Trial registration. ClinicalTrials.gov NCT05636553. Registered on December 3, 2022, and the trial is ongoing.

Sex differences are widespread during neurodevelopment and play a role in neuropsychiatric conditions such as autism, which is more prevalent in males than females. In humans, males have been shown to have larger brain volumes than females with development of the hippocampus and amygdala showing prominent sex differences. Mechanistically, sex steroids and sex chromosomes drive these differences in brain development, which seem to peak during prenatal and pubertal stages. Animal models have played a crucial role in understanding sex differences, but the study of human sex differences requires an experimental model that can recapitulate complex genetic traits. To fill this gap, human induced pluripotent stem cell–derived brain organoids are now being used to study how complex genetic traits influence prenatal brain development. For example, brain organoids from individuals with autism and individuals with X chromosome–linked Rett syndrome and fragile X syndrome have revealed prenatal differences in cell proliferation, a measure of brain volume differences, and excitatory-inhibitory imbalances. Brain organoids have also revealed increased neurogenesis of excitatory neurons due to androgens. However, despite growing interest in using brain organoids, several key challenges remain that affect its validity as a model system. In this review, we discuss how sex steroids and the sex chromosomes each contribute to sex differences in brain development. Then, we examine the role of X chromosome inactivation as a factor that drives sex differences. Finally, we discuss the combined challenges of modeling X chromosome inactivation and limitations of brain organoids that need to be taken into consideration when studying sex differences.

Background There is a policy drive in NHS maternity services to improve open disclosure with harmed families and limited information on how better practice can be achieved. Objectives To identify critical factors for improving open disclosure from the perspectives of families, doctors, midwives and services and to produce actionable evidence for service improvement. Design A three-phased, qualitative study using realist methodology. Phase 1: two literature reviews: scoping review of post-2013 NHS policy and realist synthesis of initial programme theories for improvement; an interview study with national stakeholders in NHS maternity safety and families. Phase 2: in-depth ethnographic case studies within three NHS maternity services in England. Phase 3: interpretive forums with study participants. A patient and public involvement strategy underpinned all study phases. Setting National recruitment (study phases 1 and 3); three English maternity services (study phase 2). Participants We completed n = 142 interviews, including 27 with families; 93 hours of ethnographic observations, including 52 service and family meetings over 9 months; and interpretive forums with approximately 69 people, including 11 families. Results The policy review identified a shift from viewing injured families as passive recipients to active contributors of post-incident learning, but a lack of actionable guidance for improving family involvement. The realist synthesis found weak evidence of the effectiveness of open disclosure interventions in the international maternity literature, but some improvements with organisation-wide interventions. Recent evidence was predominantly from the United Kingdom. The research identified and explored five key mechanisms for open disclosure: meaningful acknowledgement of harm; involvement of those affected in reviews/investigations; support for families’ own sense-making; psychological safely of skilled clinicians (doctors and midwives); and knowing that improvements to care have happened. The need for each family to make sense of the incident in their own terms is noted. The selective initiatives of some clinicians to be more open with some families is identified. The challenges of an adversarial medicolegal landscape and limited support for meeting incentivised targets is evidenced. Limitations Research was conducted after the pandemic, with exceptional pressure on services. Case-study ethnography was of three higher performing services: generalisation from case-study findings is limited. No observations of Health Safety Investigation Branch investigations were possible without researcher access. Family recruitment did not reflect population diversity with limited representation of non-white families, families with disabilities and other socially marginalised groups and disadvantaged groups. Conclusions We identify the need for service-wide systems to ensure that injured families are positioned at the centre of post-incident events, ensure appropriate training and post-incident care of clinicians, and foster ongoing engagement with families beyond the individual efforts made by some clinicians for some families. The need for legislative revisions to promote openness with families across NHS organisations, and wider changes in organisational family engagement practices, is indicated. Examination of how far the study’s findings apply to different English maternity services, and a wider rethinking of how family diversity can be encouraged in maternity services research. Study registration This study is registered as PROSPERO CRD42020164061. The study has been assessed following RAMESES realist guidelines. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research Programme (NIHR award ref: 17/99/85) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 22. See the NIHR Funding and Awards website for further award information. Plain language summary This study describes the experiences of families and healthcare professionals involved in incidents in NHS maternity care. The incidents caused harm-like injury or death to the baby or woman. We wanted to know whether services involved families in investigations and reviews and how this was done, what worked well, what did not work well and why. To do this, we first looked at what had already been written about ‘open disclosure’ or OD. Open disclosure is when the NHS admits to families that the care they provided has directly caused harm. After open disclosure occurs, families should be involved in making sure that the NHS learns so it can deliver better care for families in the future. In our reading, we found that families want a meaningful apology, to be involved in reviews or investigations, to know what happened to their loved one, to be cared for by knowledgeable doctors and midwives who are supported in providing open disclosure and to know things have changed because of what happened. Recommendations for involving families in open disclosure have improved, but there is still work to be done to make sure families are involved. Next, we talked to over 100 healthcare professionals involved in government policy for open disclosure in maternity services and 27 families who experienced harm. We spent 9 months observing the work of clinicians at three maternity services to watch open disclosure. We shared early findings with families, doctors, midwives and managers, and included their views. We found that services need to provide dedicated time, education and emotional support for staff who provide open disclosure. Services need to ensure that families have ongoing support and better communication about incidents. Finally, families must be involved in the review process if they want to be with their experiences reflected in reports and kept informed of ongoing improvements. Scientific summary Background A range of interventions have been introduced in the UK NHS to improve post-incident communication and support of injured families. However, there is limited evidence on the progress of this work and how improvements in open disclosure (OD) are to be embedded. Study aims and objectives The aim was to identify the critical, underlying factors for improving the incidence and quality of post-incident communication with families in NHS maternity services. This required examination of what is necessary and required in different contexts for OD processes and practices to be strengthened for families, doctors and midwives (henceforth clinicians) and service managers. Following a realist evaluation approach, the study objectives were to: establish initial hypotheses to focus investigation of OD improvements in NHS maternity services in England examine the scope of OD in NHS maternity services from the perspectives of regional and national stakeholders refine our initial hypotheses in relation to the analysis of regional and national stakeholder perspectives conduct an in-depth study of OD improvement within services verify data interpretation and study output development with different stakeholders (families, clinicians, service managers and national policy-makers). Overview of methods A qualitative study using realist evaluation methodology to evaluate the progress of OD in English NHS maternity services was conducted (May 2019–March 2022) in three sequential study phases (SPs). Realist approaches are theory-driven and designed for investigation of complex social interventions. They consider if and how an intervention works in different circumstances from the perspectives of different people. Initial hypotheses, developed from the use of a realist evaluation conceptual tool [context–mechanism–outcome (C–M–O) configurations], are developed from literature synthesis and ‘tested’ by primary research to identify potential causal relationships that explain how an intervention works. A Project Advisory Group (PAG), including families, participated in study decisions, from initial theory development, case-study sampling, data collection and interpretation of study findings against a background of rapid policy change. Primary data collection was from November 2019 to January 2022. A patient involvement and public engagement strategy sought to maximise family involvement in all stages of the study cycle. Study phase1a: literature review A scoping review examined recent (2014–22) policy recommendations for family engagement improvements in NHS maternity services. Documents were identified through database searching and included if they were related to safety, incidents, harm, reviews and investigations in maternity care. Academic papers; essays; conference abstractions, papers and presentations; and research studies were excluded. The realist synthesis of primary evidence of the progress of interventions for strengthening OD in international maternity settings included 38 documents appraised for relevance and rigour. Documents were from key database searches, included all English language sources (post 2000), without predetermined exclusion criteria for research methods. Only primary research evidence or evidence synthesis was included. Programme theories were developed with our PAG for testing during later SPs. Study phase 1b: national and regional stakeholder interview study National and regional stakeholders (n = 44), and families (n = 23), were interviewed following a topic guide developed from our literature synthesis. Families included in the study have histories of significant injury, including the stillbirth, death or serious injury of their baby and/or themselves (dating from 2007 to 2021). Study phase 2: ethnographic case studies Three maternity services in two Trusts were identified for in-depth ethnographic research by purposive sampling, based on their capacity to accommodate research immediately following the coronavirus disease 2019 (COVID-19) pandemic, and evidence of their positive deviance in improvement work on openness identified from public data sets. Across these services, we conducted: staff interviews (n = 75) and three return staff interviews, family interviews (n = 4), observations of staff and family meetings (n = 52) and observations of informal unit and office activities (all observations totalled 93 hours, with 30 hours of in-person observations). Families recruited from the case-study services had histories of significant injury dating from 2018 to 2020. We also collected and analysed locally available documentation relating to candour and being open. Study phase 3: interpretation We conducted five interpretive forums to inform the interpretation of findings. These were a forum with project advisors (n = 14), including families (n = 6), a family forum with several SP1b study participants (n = 5) and three service case-study forums, comprised of clinical and service managers and clinicians. Total forum participation was approximately n = 65. All data were managed using NVivo 20 (QSR International, Warrington, UK) and analysed concurrently by two researchers using a retroductive approach. This technique involved the ongoing examination and theorisation of findings to identify causal explanations for how, for whom, and in what ways OD might be improved. We used the five programme theories identified from the realist review to organise the analysis and reporting of our stakeholder interview and ethnographic case-study findings. Findings from our forums are included in the synthesis and discussion of findings. Results Literature reviews Our scoping review of policy documents (n = 39) identified a shift from a paternalistic view of injured families as passive recipients of care to active contributors in reviews, investigations, learning and quality improvement. Two overlapping policy trajectories were identified: one related to the Duty of Candour (DoC) and one related to maternity safety more widely. Seven themes were identified: building trust in organisations; improving systems of care and ensuring accountability; improving the safety of maternity care and saying sorry; shifting to individualised, relational care; enhancing communication; conceptualising families as active partners rather than passive recipients; and enabling families to guide the process. Although the progression of how family involvement is discussed and considered in policy is moving in a positive direction, we note the opportunity for future, specific, actionable recommendations to ensure these ideals translate into practice. In the realist synthesis, documents (n = 39) were appraised for ‘fitness-for-purpose’, that together documented primary evidence of 21 OD improvement interventions from which we identified 5 initial programme theories. Interventions documented were predominantly from USA, Australasia, and, more recently, UK sources. We identified limited evidence of the effectiveness of interventions documented. We found a difference between interventions that were adjuncts to more general safety improvement projects, and organisation-wide interventions focused on post-incident communication and care of injured families. Identified programme theories were: receiving a meaningful acknowledgement of the harm that has happened, being involved during the review/investigation process, making sense of what happened, receiving care from clinicians who are skilled and feel psychologically safe during post-incident communication and knowing that things have changed because of what has happened. Findings by programme theory Receiving a meaningful acknowledgement of the harm that has happened National stakeholders described factors that prevented or slowed improvements in initial post-incident communication and ongoing care of injured families. These were: the risks of litigation and reputational damage which may be associated with an apology and the obligation to be candid. This was particularly challenging when the extent or circumstances of injury were uncertain. Variation in the confidence and willingness of clinicians to undertake initial and ongoing disclosure with families was noted across the case studies. Alongside general medicolegal and ethical challenges to disclosure improvements, wider erosion of compassionate disclosure with families in relation to the escalation of organisational compliance in maternity safety initiatives was noted by stakeholders. Interviews with families on their post-incident experiences (2007–11) highlighted an ongoing lack of compassionate care and of prompt disclosure in many services. Many families distrusted post-incident communication, suspecting that information was being withheld. In the case-study services, the main concern for OD leads was the recovery of family trust in the service. Here, the tension between disclosure as a mandated directive and as ongoing communication was notable, with lack of investment and organisational support for the latter. A significant context of OD work was the churn of work schedules and the speed of family transfers. This complicated efforts to develop consistency of communication and care across initial, mandated and ongoing post-incident meetings, particularly where the uniqueness and flux in the needs of harmed families were paramount and families were already distrustful. These conditions led to a situation where OD was sustained as an individual and selective initiative conducted by some clinicians with some families. Being involved during the review/investigation process We examined experiences of the implementation of family engagement through the Perinatal Mortality Review Tool (PMRT) and independent Health Safety Investigation Branch (HSIB) reviews/investigations from national, in-depth, case-study perspectives. We found PMRT implementation sometimes lacked relational care for families. Additionally, families were sometimes suspicious of the independence of external incident reviews. The case-study services reported inadequacies in family inclusion, with limited proactive approaches to family involvement. A range of family involvement approaches and rationales for involvement were found across and within the case-study services, with an emphasis on families as contributing value to organisational learning for safety improvement. The tension felt by clinicians between sharing uncertain knowledge of an incident with a family and sustaining OD is identified, as is the tension between the different goals of families and services, with the former desiring answers about their case and the latter seeking system-based learning for ongoing safety improvement. Making sense of what happened We explore the practices of knowledge construction in incidents and the management of this knowledge from the perspectives of national stakeholders, staff and families. The impact of widespread organisational defensiveness over documentation sent to families, along with confusion over the purpose of reports, generated distrust. Nationally, the poor quality or inaccuracies in clinical records exacerbated differences between service and family perspectives. In the crafting of reports, during ongoing family debriefings on report findings and through informal avenues and networks, the support for families to make sense of what happened could sometimes be recovered. However, we identify the privilege and capacity required for families to gather information and garner personal networks and expertise independently of services for this to take place. Receiving care from clinicians who are skilled and feel psychologically safe during post-incident communication We identified a national underinvestment in the training of clinicians in the care of injured families and in specialist OD skills. Interviews with junior clinicians, including Band 5/6 midwives; obstetric trainees and clinical fellows, highlighted the importance of early, non-judgemental, post-incident support for junior staff. The ongoing impact of avoidable harm on clinicians is examined, along with the impact of the limited involvement of staff in Trust-level investigation and review processes. We mapped the organisation and reported use of post-incident staff support for the three case-study services and found that debriefs, organised within a few weeks of the incident, and opportunities for meeting with families were most valued by staff. Services designed or commissioned by organisations without consultation with front-line staff themselves were underused and there was also a tendency for expert clinicians to see OD work as a personal rather than a professional or service imperative. Knowing that things have changed because of what has happened The importance for injured families and staff involved in an incident to see learning and service change following an incident was clear in national and case-study findings. Demonstrating that changes were in progress was key to a service demonstrating trustworthiness to the injured family. Some injured families felt a personal responsibility to ensure that change was secured. However, in most cases, services did not maintain contact with families after their review or investigation debriefs. For some clinical leads, there was a tension between ‘quick wins’ and protracted, significant, service investment. For wider staff groups, there was a lack of effective service-level communication strategies for updating on learning and change from incidents. Embedded, ongoing multidisciplinary team meetings, where non-judgemental discussion of incidents and their effects could take place, were identified as important for establishing a wider culture of openness. The extent and tone of clinical governance (CG) outreach to front-line staff were also significant in shaping staff attitudes and behaviours towards incidents and harmed families. Discussion Realist analysis identified the significant factors and contexts that impacted efforts to strengthen OD in maternity care. We explored several layers of context influencing the progress of this work. Nationally, we identified an ongoing tension between policy prompting OD and a medicolegal context where this openness continued to place clinicians and services at reputational or legal risk. Trust-level clinical leadership and the maturation of related service approaches (notably, family and patient involvement expertise and access to post-pregnancy support pathways) played a significant role in supporting OD. For families, variations in post-incident communication and care depended on two main factors: first, the assignment of an incident to one or more national maternity safety improvement programmes that entailed particular expectations of, and processes for, family involvement, and second, the capacity of a family to proactively seek out explanations and to foster relationships for personalised support from some clinicians. In the case-study services, where some harmed families were proactive in demanding a hearing and ongoing care, and where individual clinicians reached personal judgements on a family’s entitlement to this, examples of improved OD were observed. Overall, variations in post-incident communication and support for families were explained by a lack of service investment and by individual differences in attitudes to risk and family entitlement from clinicians. Conclusions This study is the first to establish a national overview and in-depth analysis of the progress of interventions intended to support OD with families. It provides an evidence base of experiences of harmed families (incidents ranging from 2007 to 2021) and of clinicians and managers working in this field (2020–1). There are growing calls for service-level improvements in responsiveness to the experiences and needs of families post incident as well as to their calls for greater openness. However, we find that without dedicated investment in and focus on the post-incident care of families and the emotional and organisational demands of this work on clinicians; without an understanding of these needs by external agencies incentivising improvement; and without national revision in the medicolegal landscape where this work happens, candour about harm in health care will continue to divide the interests of families, staff and services. Research gaps and recommendations Research was conducted immediately after the COVID-19 pandemic, with services under considerable strain. Three high-performing services were recruited for the observational research; therefore, generalisation from findings is limited. Access to observe external (HSIB) investigations was not possible. Despite ongoing revisions to the patient and public involvement (PPI) strategy, families often marginalised by maternity services remain under-represented in this study. A multi-methods study across English maternity services to establish the validity of findings and family recruitment strategies ensuring diversity are recommended for the future. Study registration This study is registered as PROSPERO CRD42020164061. The study has been assessed following RAMESES realist guidelines. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research Programme (NIHR award ref: 17/99/85) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 22. See the NIHR Funding and Awards website for further award information.

Abstract In the United Kingdom, roughly 1 in 250 babies are stillborn each year. Most women who experience stillbirth become pregnant again – 80% within a year of loss. Presently, obstetric-led care is recommended; though there is a growing body of evidence to support provision of specialist services. The Rainbow Clinic is a specialist antenatal service providing care for pregnancies after loss incorporating clinical and psychological care. This study aimed to assess patient experience at the Rainbow Clinic and identify areas for clinical improvement. A 13-item questionnaire was distributed to pregnant women who attended the Rainbow Clinics at the Oxford Road and Wythenshawe sites of Saint Mary’s Hospital, Manchester, UK between July 2016 and June 2021. Descriptive statistics and unpaired t-test were used for quantitative data and summative content analysis for qualitative data. Four-hundred and fifty-six women completed the questionnaire. The mean patient experience score per quarter was stable with an average of 21.1 (± 3.0) for the five years, with a maximum attainable score of 25. The COVID-19 pandemic had no effect on patient experience at the Rainbow Clinic (pre-pandemic vs. during-pandemic: mean 21.2 v 21.3; p = 0.75). Free-text responses demonstrated women felt positively about the antenatal care received. Identified areas for improvement included “more awareness of the [Rainbow] sticker” to ensure women with previous loss are identified; increased publicity of the Rainbow Clinic services; developing more clinics at different locations to improve accessibility; and continuing specialist input into intrapartum care. Specialist antenatal care provided by the Rainbow Clinic was rated as of a high standard. Potential future improvements include sticker alterations (or other mechanisms to identify women who have experienced a previous loss) and develop increased awareness of the clinic in other institutions.

Introduction In the UK, 1600 babies die every year before, during or immediately after birth at 20–28 weeks’ gestation. This bereavement has a similar impact on parental physical and psychological well-being to late stillbirth (>28 weeks’ gestation). Improved understanding of potentially modifiable risk factors for late stillbirth (including supine going-to-sleep position) has influenced international clinical practice. Information is now urgently required to similarly inform clinical practice and aid decision-making by expectant mothers/parents, addressing inequalities in pregnancy loss between 20 and 28 weeks.Methods and analysis This study focuses on what portion of risk of pregnancy loss 20–28 weeks’ gestation is associated with exposures amenable to public health campaigns/antenatal care adaptation. A case–control study of non-anomalous singleton baby loss (via miscarriage, stillbirth or early neonatal death) 20+0 to 27+6 (n=316) and randomly selected control pregnancies (2:1 ratio; n=632) at group-matched gestations will be conducted. Data is collected via participant recall (researcher-administered questionnaire) and extraction from contemporaneous medical records. Unadjusted/confounder-adjusted ORs will be calculated. Exposures associated with early stillbirth at OR≥1.5 will be detectable (p0.80) assuming exposure prevalence of 30%–60%.Ethics and dissemination NHS research ethical approval has been obtained from the London—Seasonal research ethics committee (23/LO/0622). The results will be presented at international conferences and published in peer-reviewed open-access journals. Information from this study will enable development of antenatal care and education for healthcare professionals and pregnant people to reduce risk of early stillbirth.Trial registration number NCT06005272.

Abstract Background The COVID-19 pandemic has resulted in profound and far-reaching impacts on maternal and newborn care and outcomes. As part of the ASPIRE COVID-19 project, we describe processes and outcome measures relating to safe and personalised maternity care in England which we map against a pre-developed ASPIRE framework to establish the potential impact of the COVID-19 pandemic for two UK trusts. Methods We undertook a mixed-methods system-wide case study using quantitative routinely collected data and qualitative data from two Trusts and their service users from 2019 to 2021 (start and completion dates varied by available data). We mapped findings to our prior ASPIRE conceptual framework that explains pathways for the impact of COVID-19 on safe and personalised care. Results The ASPIRE framework enabled us to develop a comprehensive, systems-level understanding of the impact of the pandemic on service delivery, user experience and staff wellbeing, and place it within the context of pre-existing challenges. Maternity services experienced some impacts on core service coverage, though not on Trust level clinical health outcomes (with the possible exception of readmissions in one Trust). Both users and staff found some pandemic-driven changes challenging such as remote or reduced antenatal and community postnatal contacts, and restrictions on companionship. Other key changes included an increased need for mental health support, changes in the availability and uptake of home birth services and changes in induction procedures. Many emergency adaptations persisted at the end of data collection. Differences between the trusts indicate complex change pathways. Staff reported some removal of bureaucracy, which allowed greater flexibility. During the first wave of COVID-19 staffing numbers increased, resolving some pre-pandemic shortages: however, by October 2021 they declined markedly. Trying to maintain the quality and availability of services had marked negative consequences for personnel. Timely routine clinical and staffing data were not always available and personalised care and user and staff experiences were poorly captured. Conclusions The COVID-19 crisis magnified pre-pandemic problems and in particular, poor staffing levels. Maintaining services took a significant toll on staff wellbeing. There is some evidence that these pressures are continuing. There was marked variation in Trust responses. Lack of accessible and timely data at Trust and national levels hampered rapid insights. The ASPIRE COVID-19 framework could be useful for modelling the impact of future crises on routine care.

Abstract Background Despite progress, stillbirth rates in many high- and upper-middle income countries remain high, and the majority of these deaths are preventable. We introduce the Ending Preventable Stillbirths (EPS) Scorecard for High- and Upper Middle-Income Countries, a tool to track progress against the Lancet’s 2016 EPS Series Call to Action, fostering transparency, consistency and accountability. Methods The Scorecard for EPS in High- and Upper-Middle Income Countries was adapted from the Scorecard for EPS in Low-Income Countries, which includes 20 indicators to track progress against the eight Call to Action targets. The Scorecard for High- and Upper-Middle Income Countries includes 23 indicators tracking progress against these same Call to Action targets. For this inaugural version of the Scorecard, 13 high- and upper-middle income countries supplied data. Data were collated and compared between and within countries. Results Data were complete for 15 of 23 indicators (65%). Five key issues were identified: (1) there is wide variation in stillbirth rates and related perinatal outcomes, (2) definitions of stillbirth and related perinatal outcomes vary widely across countries, (3) data on key risk factors for stillbirth are often missing and equity is not consistently tracked, (4) most countries lack guidelines and targets for critical areas for stillbirth prevention and care after stillbirth and have not set a national stillbirth rate target, and (5) most countries do not have mechanisms in place for reduction of stigma or guidelines around bereavement care. Conclusions This inaugural version of the Scorecard for High- and Upper-Middle Income Countries highlights important gaps in performance indicators for stillbirth both between and within countries. The Scorecard provides a basis for future assessment of progress and can be used to help hold individual countries accountable, especially for reducing stillbirth inequities in disadvantaged groups.

Abstract Background Open Disclosure (OD) is open and timely communication about harmful events arising from health care with those affected. It is an entitlement of service-users and an aspect of their recovery, as well as an important dimension of service safety improvement. Recently, OD in maternity care in the English National Health Service has become a pressing public issue, with policymakers promoting multiple interventions to manage the financial and reputational costs of communication failures. There is limited research to understand how OD works and its effects in different contexts. Methods Realist literature screening, data extraction, and retroductive theorisation involving two advisory stakeholder groups. Data relevant to families, clinicians, and services were mapped to theorise the relationships between contexts, mechanisms, and outcomes. From these maps, key aspects for successful OD were identified. Results After realist quality appraisal, 38 documents were included in the synthesis (22 academic, 2 training guidance, and 14 policy report). 135 explanatory accounts were identified from the included documents (with n = 41 relevant to families; n = 37 relevant to staff; and n = 37 relevant to services). These were theorised as five key mechanism sets: (a) meaningful acknowledgement of harm, (b) opportunity for family involvement in reviews and investigations, (c) possibilities for families and staff to make sense of what happened, (d) specialist skills and psychological safety of clinicians, and (e) families and staff knowing that improvements are happening. Three key contextual factors were identified: (a) the configuration of the incident (how and when identified and classified as more or less severe); (b) national or state drivers, such as polices, regulations, and schemes, designed to promote OD; and (c) the organisational context within which these these drivers are recieived and negotiated. Conclusions This is the first review to theorise how OD works, for whom, in what circumstances, and why. We identify and examine from the secondary data the five key mechanisms for successful OD and the three contextual factors that influence this. The next study stage will use interview and ethnographic data to test, deepen, or overturn our five hypothesised programme theories to explain what is required to strengthen OD in maternity services.

ObjectiveCurrent data on the role of the umbilical cord in pregnancy complications are conflicting; estimates of the proportion of stillbirths due to cord problems range from 3.4 to 26.7%. A systematic review and meta-analysis were undertaken to determine which umbilical cord abnormalities are associated with stillbirth and related adverse pregnancy outcomes.MethodsMEDLINE, EMBASE, CINAHL and Google Scholar were searched from 1960 to present day. Reference lists of included studies and grey literature were also searched. Cohort, cross-sectional, or case-control studies of singleton pregnancies after 20 weeks' gestation that reported the frequency of umbilical cord characteristics or cord abnormalities and their relationship to stillbirth or other adverse outcomes were included. Quality of included studies was assessed using NIH quality assessment tools. Analyses were performed in STATA.ResultsThis review included 145 studies. Nuchal cords were present in 22% of births (95% CI 19, 25); multiple loops of cord were present in 4% (95% CI 3, 5) and true knots of the cord in 1% (95% CI 0, 1) of births. There was no evidence for an association between stillbirth and any nuchal cord (OR 1.11, 95% CI 0.62, 1.98). Comparing multiple loops of nuchal cord to single loops or no loop gave an OR of 2.36 (95% CI 0.99, 5.62). We were not able to look at the effect of tight or loose nuchal loops. The likelihood of stillbirth was significantly higher with a true cord knot (OR 4.65, 95% CI 2.09, 10.37).ConclusionsTrue umbilical cord knots are associated with increased risk of stillbirth; the incidence of stillbirth is higher with multiple nuchal loops compared to single nuchal cords. No studies reported the combined effects of multiple umbilical cord abnormalities. Our analyses suggest specific avenues for future research.

Abstract Background: Pregnancy is often conceptualised as a ‘teachable moment’ for health behaviour change. However, it is likely that different stages of pregnancy, and individual antenatal events, provide multiple distinct teachable moments to prompt behaviour change. Whilst previous quantitative research supports this argument, it is unable to provide a full understanding of the nuanced factors influencing eating behaviour. The aim of this study was to explore influences on women’s eating behaviour throughout pregnancy. Methods: In-depth interviews were conducted online with 25 women who were less than six-months postpartum. Interviews were audio-recorded and transcribed verbatim. Data were analysed thematically. Results: Five themes were generated from the data that capture influences on women’s eating behaviour throughout pregnancy: ‘The preconceptual self’, ‘A desire for good health’, ‘Retaining control’, ‘Relaxing into pregnancy’, and ‘The lived environment’. Conclusion: Mid-pregnancy may provide a more salient opportunity for eating behaviour change than other stages of pregnancy. Individual antenatal events, such as the glucose test, can also prompt change. In clinical practice, it will be important to consider the changing barriers and facilitators operating throughout pregnancy, and to match health advice to stages of pregnancy, where possible. Existing models of teachable moments may be improved by considering the dynamic nature of pregnancy, along with the influence of the lived environment, pregnancy symptoms, and past behaviour. These findings provide an enhanced understanding of the diverse influences on women’s eating behaviour throughout pregnancy and provide a direction for how to adapt existing theories to the context of pregnancy.

Objectives Theoretical models have informed the understanding of pregnancy as a ‘teachable moment’ for health behaviour change. However, these models have not been developed specifically for, nor widely tested, in this population. Currently, no pregnancy-specific model of behaviour change exists, which is important given it is a unique yet common health event. This study aimed to assess the extent to which factors influencing antenatal behaviour change are accounted for by the COM-B model and Teachable Moments (TM) model and to identify which model is best used to understand behaviour change during pregnancy. Design Theoretical mapping exercise. Methods A deductive approach was adopted; nine sub-themes identified in a previous thematic synthesis of 92 studies were mapped to the constructs of the TM and COM-B models. The sub-themes reflected factors influencing antenatal health behaviour. Findings All sub-themes mapped to the COM-B model constructs, whereas the TM model failed to incorporate three sub-themes. Missed factors were non-psychological, including practical and environmental factors, social influences, and physical pregnancy symptoms. In contrast to the COM-B model, the TM model provided an enhanced conceptual understanding of pregnancy as a teachable moment for behaviour change, however, neither model accounted for the changeable salience of influencing factors throughout the pregnancy experience. Conclusions The TM and COM-B models are both limited when applied within the context of pregnancy. Nevertheless, both models offer valuable insight that should be drawn upon when developing a pregnancy-specific model of behaviour change.

Aim: Pregnancy after the death of a baby is associated with numerous, varied psychological challenges for pregnant women. This study aimed to explore women’s experiences of pregnancy whilst attending a specialist antenatal service for pregnancies after a perinatal death. Methods: Semi-structured interviews with twenty women in a subsequent pregnancy after a perinatal death were conducted and analyzed taking an inductive thematic analysis approach. Results: All women expressed a heightened “awareness of risk”. Two subthemes demonstrated how increased awareness of risk affected their experience and their desire regarding antenatal and postnatal support. Women talked about stillbirth being a “quiet, unspoken subject” causing them internal conflict as they had an awareness of pregnancy complications that other people did not. Navigating subsequent pregnancies relied on them “expecting the worst and hoping for the best” in terms of pregnancy outcomes. Women viewed specialist antenatal care in pregnancy after perinatal loss favorably, as it enabled them to receive tailored care that met their needs stemming from their increased awareness of and personal expectations of risk. Conclusion: Women’s experiences can be used to develop models of care but further studies are required to determine to identify which components are most valued.

Abstract Background Around 1 in 150 babies are stillborn or die in the first month of life in the UK. Most women conceive again, and subsequent pregnancies are often characterised by feelings of stress and anxiety, persisting beyond the birth. Psychological distress increases the risk of poor pregnancy outcomes and longer-term parenting difficulties. Appropriate emotional support in subsequent pregnancies is key to ensure the wellbeing of women and families. Substantial variability in existing care has been reported, including fragmentation and poor communication. A new care package improving midwifery continuity and access to emotional support during subsequent pregnancy could improve outcomes. However, no study has assessed the feasibility of a full-scale trial to test effectiveness in improving outcomes and cost-effectiveness for the National Health Service (NHS). Methods A prospective, mixed-methods pre-and post-cohort study, in two Northwest England Maternity Units. Thirty-eight women, (≤ 20 weeks’ gestation, with a previous stillbirth, or neonatal death) were offered the study intervention (allocation of a named midwife care coordinator and access to group and online support). Sixteen women receiving usual care were recruited in the 6 months preceding implementation of the intervention. Outcome data were collected at 2 antenatal and 1 postnatal visit(s). Qualitative interviews captured experiences of care and research processes with women (n = 20), partners (n = 5), and midwives (n = 8). Results Overall recruitment was 90% of target, and 77% of women completed the study. A diverse sample reflected the local population, but non-English speaking was a barrier to participation. Study processes and data collection methods were acceptable. Those who received increased midwifery continuity valued the relationship with the care coordinator and perceived positive impacts on pregnancy experiences. However, the anticipated increase in antenatal continuity for direct midwife contacts was not observed for the intervention group. Take-up of in-person support groups was also limited. Conclusions Women and partners welcomed the opportunity to participate in research. Continuity of midwifery care was supported as a beneficial strategy to improve care and support in pregnancy after the death of a baby by both parents and professionals. Important barriers to implementation included changes in leadership, service pressures and competing priorities. Trial registration ISRCTN17447733 first registration 13/02/2018.

BackgroundLate stillbirth, which occurs ≥28 weeks' gestation, affects 1.3-8.8 per 1000 births in high-income countries. Of concern, most occur in women without established risk factors. Identification of potentially modifiable risk factors that relate to maternal behaviors remains a priority in stillbirth prevention research. This study aimed to investigate, in an international cohort, whether maternal sleep practices are related to late stillbirth.MethodsAn Internet-based case-control study of women who had a stillbirth ≥28 weeks' gestation within 30 days before completing the survey (n = 153) and women with an ongoing third-trimester pregnancy or who had delivered a live born child within 30 days (n = 480). Bivariate and multivariate logistic regressions were used to determine unadjusted and adjusted odds ratios (OR and aOR, respectively) with 95% confidence intervals (95% CIs) for stillbirth.ResultsSleeping >9 hours per night in the previous month was associated with stillbirth (aOR 1.75 [95% CI 1.10-2.79]), as was waking on the right side (2.27 [1.31-3.92]). Nonrestless sleep in the last month was also found to be associated with stillbirth (1.73 [1.03-2.99]), with good sleep quality in the last month approaching significance (1.64 [0.98-2.75]). On the last night of pregnancy, not waking more than one time was associated with stillbirth (2.03 [1.24-3.34]). No relationship was found with going to sleep position during pregnancy, although very few women reported settling in the supine position (2.4%).ConclusionsLong periods of undisturbed sleep are associated with late stillbirth. Physiological studies of how the neuroendocrine and autonomic system pathways are regulated during sleep in the context of late pregnancy are warranted.

IntroductionSupine sleep position is associated with stillbirth, likely secondary to inferior vena cava compression, and a reduction in cardiac output (CO) and uteroplacental perfusion. Evidence for the effects of prone position in pregnancy is less clear. This study aimed to determine the effect maternal prone position on maternal haemodynamics and fetal heart rate, compared with left lateral position.MethodsTwenty-one women >28 weeks' gestation underwent non-invasive CO monitoring (Cheetah) every 5 minutes and continuous fetal heart rate monitoring (MONICA) in left lateral (20 minutes), prone (30 minutes), followed by left lateral (20 minutes). Anxiety and comfort were assessed by questionnaires. Regression analyses (adjusted for time) compared variables between positions. The information derived from the primary study was used in an existing mathematical model of maternal circulation in pregnancy, to determine whether occlusion of the inferior vena cava could account for the observed effects. In addition, a scoping review was performed to identify reported clinical, haemodynamic and fetal effects of maternal prone position; studies were included if they reported clinical outcomes or effects or maternal prone position in pregnancy. Study records were grouped by publication type for ease of data synthesis and critical analysis. Meta-analysis was performed where there were sufficient studies.ResultsMaternal blood pressure (BP) and total vascular resistance (TVR) were increased in prone (sBP 109 vs 104 mmHg, p = 0.03; dBP 74 vs 67 mmHg, p = 0.003; TVR 1302 vs 1075 dyne.s-1cm-5, p = 0.03). CO was reduced in prone (5.7 vs 7.1 mL/minute, p = 0.003). Fetal heart rate, variability and decelerations were unaltered. However, fetal accelerations were less common in prone position (86% vs 95%, p = 0.03). Anxiety was reduced after the procedure, compared to beforehand (p = 0.002), despite a marginal decline in comfort (p = 0.04).The model predicted that if occlusion of the inferior vena cava occurred, the sBP, dBP and CO would generally decrease. However, the TVR remained relatively consistent, which implies that the MAP and CO decrease at a similar rate when occlusion occurs. The scoping review found that maternal and fetal outcomes from 47 included case reports of prone positioning during pregnancy were generally favourable. Meta-analysis of three prospective studies investigating maternal haemodynamic effects of prone position found an increase in sBP and maternal heart rate, but no effect on respiratory rate, oxygen saturation or baseline fetal heart rate (though there was significant heterogeneity between studies).ConclusionProne position was associated with a reduction in CO but an uncertain effect on fetal wellbeing. The decline in CO may be due to caval compression, as supported by the computational model. Further work is needed to optimise the safety of prone positioning in pregnancy.Trial registrationThis trial was registered at clinicaltrials.gov (NCT04586283).

Abstract Background The AFFIRM intervention aimed to reduce stillbirth and neonatal deaths by increasing awareness of reduced fetal movements (RFM) and implementing a care pathway when women present with RFM. Although there is uncertainty regarding the clinical effectiveness of the intervention, the aim of this analysis was to evaluate the cost-effectiveness. Methods A stepped-wedge, cluster-randomised trial was conducted in thirty-three hospitals in the United Kingdom (UK) and Ireland. All women giving birth at the study sites during the analysis period were included in the study. The costs associated with implementing the intervention were estimated from audits of RFM attendances and electronic healthcare records. Trial data were used to estimate a cost per stillbirth prevented was for AFFIRM versus standard care. A decision analytic model was used to estimate the costs and number of perinatal deaths (stillbirths + early neonatal deaths) prevented if AFFIRM were rolled out across Great Britain for one year. Key assumptions were explored in sensitivity analyses. Results Direct costs to implement AFFIRM were an estimated £95,126 per 1,000 births. Compared to standard care, the cost per stillbirth prevented was estimated to be between £86,478 and being dominated (higher costs, no benefit). The estimated healthcare budget impact of implementing AFFIRM across Great Britain was a cost increase of £61,851,400/year. Conclusions Perinatal deaths are relatively rare events in the UK which can increase uncertainty in economic evaluations. This evaluation estimated a plausible range of costs to prevent baby deaths which can inform policy decisions in maternity services. Trial registration The trial was registered with www.ClinicalTrials.gov , number NCT01777022 .

Background Objective Search Strategy Selection Criteria Data Collection and Analysis Main Results Conclusions Health literacy, influenced by sociodemographic characteristics such as ethnicity, economic means and societal factors, affects the ways in which pregnant women maintain their health; this in turn may increase risk of adverse pregnancy outcomes.To explore what is known about the impact of personal health literacy on prevention of stillbirth and related adverse outcomes in pregnant women of low socioeconomic status or from ethnic minority backgrounds.MEDLINE, CINAHL, PsychINFO, and CENTRAL were searched as well as reference lists of included studies and gray literature.Included studies focused on personal health literacy and stillbirth prevention in women from low socioeconomic or ethnic minority backgrounds in the perinatal period.A meta‐summary approach was adopted for qualitative, observational, descriptive, and audit studies. Findings of intervention studies were extracted, and meta‐analyses were conducted where possible. The primary outcome was stillbirth; maternal mortality and neonatal mortality were secondary outcomes.Forty‐one studies were included from diverse geographical settings. The meta‐summary synthesized five abstracted statements. These recognized lower personal health literacy and greater difficulty interacting with healthcare services in the studied populations, primarily as the result of limited health knowledge, lack of positive perception towards health services, language barriers, illiteracy, and relying on friends or family members for health information. Meta‐analysis of intervention studies revealed no association between current interventions that aimed to increase personal health literacy and the risk of stillbirth (relative risk [RR] 1.04, 95% confidence interval [CI] 0.96–1.12), neonatal mortality (RR 0.88, 95% CI 0.75–1.03), and maternal mortality (RR 0.87, 95% CI 0.63–1.22).Various factors suggest lower personal health literacy in women of low socioeconomic status or ethnic minority, which can increase the risk of stillbirth. However, this review identified no significant impact of current health education interventions on the risk of stillbirth, or neonatal or maternal mortality. Although not directly measured, the health education interventions were anticipated to increase personal health literacy. Further research on the topic of this scoping review is warranted, particularly in lower‐resource settings and regarding the potential role of e‐literacy and organizational health literacy to improve pregnancy outcomes. To address deficits in health literacy, efforts must be made to provide pregnant women with health information in novel, accessible ways. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the risk of stillbirth in relation to (1) a previous caesarean delivery (CD) compared with those following a vaginal birth (VB); and (2) vaginal birth after caesarean (VBAC) compared with a repeat CD. Design: Population‐based cohort study. Setting: The Swedish Medical Birth registry. Population: Women with their first and second singletons between 1982 and 2012. Methods: Multivariable logistic regression models were performed to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CI) of the association between CD in the first pregnancy and stillbirth in the second pregnancy and the association between VBAC and stillbirth. Sub‐group analyses were performed by types of CD and timing of stillbirth (antepartum and intrapartum). Main outcome measures: Stillbirth (antepartum and intrapartum fetal death). Results: Of the 1 771 700 singleton births from 885 850 women, 117 114 (13.2%) women had a CD in the first pregnancy, and 51 755 had VBAC in the second pregnancy. We found a 37% increased odds of stillbirth (aOR 1.37; 95% CI 1.23–1.52) in women with a previous CD compared with VB. The odds of intrapartum stillbirth were higher in the previous pre‐labour CD group (aOR 2.72; 95% CI 1.51–4.91) and in the previous in‐labour CD group (aOR 1.35; 95% CI 0.76–2.40), although not statistically significant in the latter case. No increased odds were found for intrapartum stillbirth in women who had VBAC (aOR 0.99; 95% CI 0.48–2.06) compared with women who had a repeat CD. Conclusions: This study confirms that a CD is associated with an increased risk of subsequent stillbirth, with a greater risk among pre‐labour CD. This association is not solely mediated by increases in intrapartum asphyxia, uterine rupture or attempted VBAC. Further research is needed to understand this association, but these findings might help healthcare providers to reach optimal decisions regarding mode of birth, particularly when CD is unnecessary. Linked article: This article is commented on by Pisake Lumbiganon et al., pp. 1062‐1063 in this issue. To view this mini commentary visit https://doi.org/10.1111/1471‐0528.17795. [ABSTRACT FROM AUTHOR]

Abstract Background Concerns regarding reduced fetal movements (RFM) are reported in 5–15% of pregnancies, and RFM are associated with adverse pregnancy outcomes including fetal growth restriction and stillbirth. Studies have aimed to improve pregnancy outcomes by evaluating interventions to raise awareness of RFM in pregnancy, such as kick counting, evaluating interventions for the clinical management of RFM, or both. However, there is not currently a core outcome set (COS) for studies of RFM. This study aims to create a COS for use in research studies that aim to raise awareness of RFM and/or evaluate interventions for the clinical management of RFM. Methods A systematic review will be conducted, to identify outcomes used in randomised and non-randomised studies with control groups that aimed to raise awareness of RFM (for example by using mindfulness techniques, fetal movement counting, or other tools such as leaflets or mobile phone applications) and/or that evaluated the clinical management of RFM. An international Delphi consensus will then be used whereby stakeholders will rate the importance of the outcomes identified in the systematic review in (i) awareness and (ii) clinical management studies. The preliminary lists of outcomes will be discussed at a consensus meeting where one final COS for awareness and management, or two discrete COS (one for awareness and one for management), will be agreed upon. Discussion A well-developed COS will provide researchers with the minimum set of outcomes that should be measured and reported in studies that aim to quantify the effects of interventions.

Abstract Background The grief associated with the death of a baby is enduring, however most women embark on another pregnancy, many in less than a year following their loss. Symptoms of anxiety and depression are reported to be increased in pregnancies after perinatal death, although effect on maternal stress is less clear. Variation between individual studies may result from differences in gestation at sampling, the questionnaire used and the type of antecedent perinatal death. We aimed to describe quantitative measures of anxiety, depression, stress and quality of life at different timepoints in pregnancies after perinatal death and in the early postnatal period. Methods Women recruited from three sites in the North-West of England. Women were asked to participate if a previous pregnancy had ended in a perinatal death. Participants completed validated measures of psychological state (Cambridge Worry Score, Edinburgh Postnatal Depression Score (EPDS), Generalized Anxiety Disorder 7-item score) and health status (EQ-5D-5L™ and EQ5D-Visual Analogue Scale) at three time points, approximately 15 weeks’ and 32 weeks’ gestation and 6 weeks postnatally. A sample of hair was taken at approximately 36 weeks’ gestation for measurement of hair cortisol in a subgroup of women. The hair sample was divided into samples from each trimester and cortisol measured by ELISA. Results In total 112 women participated in the study. Measures of anxiety and depressive symptoms decreased from the highest levels at 15 weeks’ gestation to 6-weeks postnatal (for example mean GAD-7: 15 weeks 8.2 ± 5.5, 6 weeks postnatal 4.4 ± 5.0, p

Highlights Detection and treatment of pregnancies at high risk of fetal growth restriction (FGR) and stillbirth remains a major obstetric challenge; circulating maternal serum microRNAs (miRNAs) offer potential as novel biomarkers. Unbiased analysis of serum miRNAs in women in late pregnancy identified a specific profile of circulating miRNAs in women with a growth-restricted infant. Some altered miRNAs (miR-28-5p, miR-301a-3p) showed sexually dimorphic expression in FGR pregnancies and others a fetal-sex dependent association to a hormonal marker of placental dysfunction (miR-454-3p, miR-29c-3p). miR-301a-3p and miR-28-5p could potentially be used to predict FGR specifically in pregnancies with a male or female baby, respectively, however larger cohort studies are required. Further investigations of these miRNAs and their relationship to placental dysfunction will lead to a better understanding of the pathophysiology of FGR and why there is differing susceptibility of male and female fetuses to FGR and stillbirth.

Abstract Background Late stillbirth continues to affect 3–4/1000 pregnancies in high-resource settings, with even higher rates in low-resource settings. Reduced foetal movements are frequently reported by women prior to foetal death, but there remains a poor understanding of the reasons and how to deal with this symptom clinically, particularly during the preterm phase of gestation. We aimed to determine which women are at the greatest odds of stillbirth in relation to the maternal report of foetal movements in late pregnancy (≥ 28 weeks’ gestation). Methods This is an individual participant data meta-analysis of all identified case-control studies of late stillbirth. Studies included in the IPD were two from New Zealand, one from Australia, one from the UK and an internet-based study based out of the USA. There were a total of 851 late stillbirths, and 2257 controls with ongoing pregnancies. Results Increasing strength of foetal movements was the most commonly reported (> 60%) pattern by women in late pregnancy, which were associated with a decreased odds of late stillbirth (adjusted odds ratio (aOR) = 0.20, 95% CI 0.15 to 0.27). Compared to no change in strength or frequency women reporting decreased frequency of movements in the last 2 weeks had increased odds of late stillbirth (aOR = 2.33, 95% CI 1.73 to 3.14). Interaction analysis showed increased strength of movements had a greater protective effect and decreased frequency of movements greater odds of late stillbirth at preterm gestations (28–36 weeks’ gestation). Foetal hiccups (aOR = 0.45, 95% CI 0.36 to 0.58) and regular episodes of vigorous movement (aOR = 0.67, 95% CI 0.52 to 0.87) were associated with decreased odds of late stillbirth. A single episode of unusually vigorous movement was associated with increased odds (aOR = 2.86, 95% CI 2.01 to 4.07), which was higher in women at term. Conclusions Reduced foetal movements are associated with late stillbirth, with the association strongest at preterm gestations. Foetal hiccups and multiple episodes of vigorous movements are reassuring at all gestations after 28 weeks’ gestation, whereas a single episode of vigorous movement is associated with stillbirth at term.

Abstract Background Advanced maternal age (≥35 years) is associated with increased rates of adverse pregnancy outcome. Better understanding of underlying pathophysiological processes may improve identification of older mothers who are at greatest risk. This study aimed to investigate changes in oxidative stress and inflammation in older women and identify clinical and biochemical predictors of adverse pregnancy outcome in older women. Methods The Manchester Advanced Maternal Age Study (MAMAS) was a multicentre, observational, prospective cohort study of 528 mothers. Participants were divided into three age groups for comparison 20–30 years (n = 154), 35–39 years (n = 222) and ≥ 40 years (n = 152). Demographic and medical data were collected along with maternal blood samples at 28 and 36 weeks’ gestation. Multivariable analysis was conducted to identify variables associated with adverse outcome, defined as one or more of: small for gestational age (

Introduction Women from ethnic minority groups are at more risk of adverse outcomes in pregnancy compared with those from white British groups; suboptimal care may contribute to this increased risk. This study aimed to examine serious clinical incidents at two maternity units to explore causative factors for women from ethnic minorities and determine whether these differed from white women.Methods A retrospective review was conducted of all serious incidents (n=36) occurring in a large National Health Service maternity provider (~14 000 births per annum) between 2018 and 2020. Data were collected from case records for variables which could mediate the association between ethnicity and adverse outcome. The incident reviews were blinded and reviewed by two independent investigators and data regarding root causes and contributory factors were extracted.Results Fourteen of the 36 incidents (39%) occurred in women from minority ethnic groups, which is comparable to the maternity population. Women involved in serious clinical incidents frequently had pre-existing medical or obstetric complications. Booking after 12 weeks’ gestation occurred more frequently in women from minority ethnic groups than in the background population. There were differences in root causes of serious incidents between groups, a lack of situational awareness was the most frequent cause in white women and staff workload was most frequent in women from minority ethnic groups. Communication issues and detection of deterioration were similar between the two groups.Discussion Although there was no difference in the proportion of serious incidents between the groups, there were differences in medical and pregnancy-related risk factors between groups and in the root causes identified. Efforts are needed to ensure equity of early access to antenatal care and to ensure that there is adequate staffing to ensure that women’s needs are met; this is particularly cogent when there are complex medical or social needs.

Abstract Introduction 98% of the 2.6 million stillbirths per annum occur in low and middle income countries. However, understanding of risk factors for stillbirth in these settings is incomplete, hampering efforts to develop effective strategies to prevent deaths. Methods A cross-sectional study of eligible women on the postnatal ward at Mpilo Hospital, Zimbabwe was undertaken between 01/08/2018 and 31/03/2019 (n = 1779). Data were collected from birth records for maternal characteristics, obstetric and past medical history, antenatal care and pregnancy outcome. A directed acyclic graph was constructed with multivariable logistic regression performed to fit the corresponding model specification to data comprising singleton pregnancies, excluding neonatal deaths (n = 1734), using multiple imputation for missing data. Where possible, findings were validated against all women with births recorded in the hospital birth register (n = 1847). Results Risk factors for stillbirth included: previous stillbirth (29/1691 (2%) of livebirths and 39/43 (91%) of stillbirths, adjusted Odds Ratio (aOR) 2628.9, 95% CI 342.8 to 20,163.0), antenatal care (aOR 44.49 no antenatal care vs. > 4 antenatal care visits, 95% CI 6.80 to 291.19), maternal medical complications (aOR 7.33, 95% CI 1.99 to 26.92) and season of birth (Cold season vs. Mild aOR 14.29, 95% CI 3.09 to 66.08; Hot season vs. Mild aOR 3.39, 95% CI 0.86 to 13.27). Women who had recurrent stillbirth had a lower educational and health status (18.2% had no education vs. 10.0%) and were less likely to receive antenatal care (20.5% had no antenatal care vs. 6.6%) than women without recurrent stillbirth. Conclusion The increased risk in women who have a history of stillbirth is a novel finding in Low and Middle Income Countries (LMICs) and is in agreement with findings from High Income Countries (HICs), although the estimated effect size is much greater (OR in HICs ~ 5). Developing antenatal care for this group of women offers an important opportunity for stillbirth prevention.