International Perspectives of Extended Genetic Sequencing When Used as Part of Newborn Screening to Identify Cystic Fibrosis.

There is increasing interest in using extended genetic sequencing (EGS) in newborn screening (NBS) for cystic fibrosis (CF). How this is implemented will change the number of children being given an uncertain outcome of CRMS/CFSPID (cystic fibrosis transmembrane conductance regulator (CFTR)-related metabolic syndrome/CF Screen Positive Inconclusive Diagnosis), probable carrier results, and the number of missed CF diagnoses. An international survey of CF health professionals was used to gather views on two approaches to EGS-specific (may reduce detection of CRMS/CFSID but miss some CF cases) versus sensitive (may increase detection of CRMS/CFSPID but avoid missing more CF cases). Health professionals acknowledged the anxiety caused to parents (and health professionals) from the uncertainty surrounding the prognosis and management of CRMS/CFSPID. However, most preferred the sensitive approach, as overall, identifying more cases of CRMS/CFSPID was viewed as less physically and psychologically damaging than a missed case of CF. The importance of early diagnosis and treatment for CF to ensure better health outcomes and reducing diagnostic odysseys for parents were highlighted. A potential benefit to identifying more children with CRMS/CFSPID included increasing knowledge to obtain a better understanding of how these children should best be managed in the future.

A mixed-methods study of women's birthplace preferences and decisions in England.

PROBLEM: Choice has been a key aspect of maternity care policy in England since 1993, however a gap remains between the birthplaces women want and where they actually give birth. BACKGROUND: The latest maternity care policy in England acknowledges that women are not being given 'real choice' in their care and often being told what to do. This is problematic since unfulfilled preferences have been linked to negative childbirth experiences. AIM: To understand the factors affecting women's birthplace preferences and decisions, and why these might differ. METHODS: A sequential mixed-methods study consisting of an online questionnaire (n=49) and follow-up interviews (n=14) with women who were either currently pregnant or had recently given birth in a metropolitan region in England. FINDINGS: Most women in this study said that they would prefer to give birth in an alongside maternity unit because it offered a compromise between the risk of poor outcomes and risk of unnecessary medicalisation. However, the majority of women's preferences were medicalised at the point of decision-making as the minimisation of clinical risk was ultimately prioritised. DISCUSSION: Women's preference for the alongside maternity unit demonstrates the growing popularity for this less medicalised, 'alternative' birthplace option. However pre-existing conditions, reproductive histories and experiential knowledge influence women's decision to give birth in the labour ward and suggests that minimising clinical risk is women's key priority. CONCLUSION: Women navigate complex and competing discourses when forming childbirth preferences and making decisions, selectively considering different risks and knowledges to make the decisions right for them.

Stakeholder Views of the Proposed Introduction of Next Generation Sequencing into the Cystic Fibrosis Screening Protocol in England.

The project aimed to gather, analyse, and compare the views of stakeholders about the proposed UK cystic fibrosis (CF) screening protocol incorporating next generation sequencing (NGS). The study design was based on principles of Q-methodology with a willingness-to-pay exercise. Participants were recruited from 12 CF centres in the UK. The study contained twenty-eight adults who have experience with CF (parents of children with CF (n = 21), including parents of children with CF transmembrane conductance regulator (CFTR)-related metabolic syndrome (CRMS)/CF screen positive-inconclusive diagnosis (CFSPID), an uncertain outcome (n = 3), and adults with CF (n = 4)), and nine health professionals involved in caring for children with CF. Parents and health professionals expressed a preference for a sensitive approach to NGS. This was influenced by the importance participants placed on not missing any children with CF via screening and the balance of harm between missing a case of CF compared to picking up more children with an uncertain outcome (CRMS/CFSPID). Given the preference for a sensitive approach, the need for adequate explanations about potential outcomes including uncertainty (CFSPID) at the time of screening was emphasized. More research is needed to inform definitive guidelines for managing children with an uncertain outcome following CF screening.

General population screening for paediatric type 1 diabetes-A qualitative study of UK professional stakeholders.

AIMS: Identifying children at risk of type 1 diabetes allows education for symptom recognition and monitoring to reduce the risk of diabetic ketoacidosis at presentation. We aimed to explore stakeholder views towards paediatric general population screening for type 1 diabetes in the United Kingdom (UK). METHODS: Qualitative interviews were undertaken with 25 stakeholders, including diabetes specialists, policymakers and community stakeholders who could be involved in a future type 1 diabetes screening programme in the UK. A thematic framework analysis was performed using the National Screening Committee's evaluative criteria as the overarching framework. RESULTS: Diabetic ketoacidosis prevention was felt to be a priority and proposed benefits of screening included education, monitoring and helping the family to better prepare for a future with type 1 diabetes. However, diabetes specialists were cautious about general population screening because of lack of evidence for public acceptability. Concerns were raised about the harms of living with risk, provoking health anxiety and threatening the child's right to an 'open future'. Support systems that met the clinical and psychological needs of the family living with risk were considered essential. Stakeholders were supportive of research into general population screening and acknowledged this would be a priority if an immunoprevention agent were licensed in the UK. CONCLUSIONS: Although stakeholders suggested the harms of UK paediatric general population screening currently outweigh the benefits, this view would potentially be altered if prevention therapies were licensed. In this case, an evidence-based screening strategy would need to be formulated and public acceptability explored.

Expressivist objections to prenatal screening and testing: Perceptions of people living with disability.

The 'expressivist objection' (EO) refers to the notion that using reproductive (genetic) technologies to prevent the birth of future would-be disabled people contain, and express, a negative valuation of life with disability. Whilst the EO has received increased attention in recent years in line with rapid technological and genomic developments, there remains scant research on how EO concerns are experienced and expressed by disabled people and their families, especially within and between impairment groups. Bringing together two studies-one with adults and family members living with genetic conditions (n = 62) and one with parents of children with Down's syndrome (n = 22)-we argue that disabled people and their families variously embrace, reject or rework the EO across contexts, and yet also frequently situate it within broad support for reproductive technologies. We present three key factors that mediate responses to the EO: (1) the nature of impairment and its integration within identity; (2) social and cultural contexts relating to disability and (3) the (individual and collective) imagined futures of disabled people. In so doing, we blend the conceptual architecture of medical sociology and disability studies, arguing that this allows us to accurately illuminate the nuanced responses of disabled people and their families.

Benefits and harms adopted by health economic assessments evaluating antenatal and newborn screening programmes in OECD countries: A systematic review of 336 articles and reports.

BACKGROUND: Health economic assessments are used to determine whether the resources needed to generate net benefit from a screening programme, driven by multiple complex benefits and harms, are justifiable. We systematically identified the benefits and harms incorporated within economic assessments evaluating antenatal and newborn screening programmes. METHODS: For this systematic review and thematic analysis, we searched the published and grey literature from January 2000 to January 2021. Studies that included an economic evaluation of an antenatal or newborn screening programme in an OECD country were eligible. We identified benefits and harms using an integrative descriptive analysis, and illustrated a thematic framework. (Systematic review registration PROSPERO, CRD42020165236). FINDINGS: The searches identified 52,244 articles and reports and 336 (242 antenatal and 95 newborn) were included. Eighty-six subthemes grouped into seven themes were identified: 1) diagnosis of screened for condition, 2) life years and health status adjustments, 3) treatment, 4) long-term costs, 5) overdiagnosis, 6) pregnancy loss, and 7) spillover effects on family members. Diagnosis of screened for condition (115 studies, 47.5%), life-years and health status adjustments (90 studies, 37.2%) and treatment (88 studies, 36.4%) accounted for most of the benefits and harms evaluating antenatal screening. The same themes accounted for most of the benefits and harms included in studies assessing newborn screening. Overdiagnosis and spillover effects tended to be ignored. INTERPRETATION: Our proposed framework can be used to guide the development of future health economic assessments evaluating antenatal and newborn screening programmes, to prevent exclusion of important potential benefits and harms.

EarLy Surveillance for Autoimmune diabetes: protocol for a qualitative study of general population and stakeholder perspectives on screening for type 1 diabetes in the UK (ELSA 1).

OBJECTIVE: Type 1 diabetes (T1D) is the most common form of diabetes in children, accounting for 96% of cases, with 29 000 children affected in the UK. Studies have recently identified immunotherapies that safely delay the development of T1D for at least 3 years, and further therapies are in development. General population screening programs in other countries can now accurately identify children with presymptomatic T1D who can be entered into prevention studies. The UK does not have such a system in place. We aim to explore whether parents and children in the UK would want to be part of such a program of testing for T1D in the general population, how they would want to be informed and participate in such a program, and how any barriers to recruitment and participation can be addressed. Additionally, the views of stakeholders who would be involved in the testing program will be collected and analyzed. RESEARCH DESIGN AND METHODS: We will interview parents/guardians and children aged 3-13 years about their views on screening for T1D. We will recruit purposefully to ensure representation across ethnicities and socioeconomic groups. Interviews will be transcribed, analyzed and used to inform iterative co-design work with additional families to address any issues raised. Similar qualitative work will be undertaken with professional stakeholders who would be involved in implementing any future screening program. Where possible, all aspects of this study will be performed remotely by phone or online to minimize infection risk. CONCLUSIONS: This qualitative study will provide the first insights into acceptability of testing and monitoring for T1D in the general population from the perspective of families and stakeholders in the UK. Co-design work will help establish the barriers and identify strategies to mitigate and overcome these issues, as an important step towards consideration of national testing for T1D.

'We're kind of like genetic nomads': Parents' experiences of biographical disruption and uncertainty following in/conclusive results from newborn cystic fibrosis screening.

As whole genome sequencing is being considered as a tool to deliver expanded newborn screening (NBS) globally, the range of equivocal results it could produce are gaining increased attention. For cystic fibrosis (CF) screening, the use of next generation sequencing within existing UK NBS programmes would increase the number of uncertain designations returned within results, including that of Cystic Fibrosis Screen Positive Inconclusive Diagnosis (CFSPID). However, the experiences of families already living with this designation have been under-explored. This study uses in-depth interviews to explore the perspectives of sixteen parents who received positive results from CF NBS, with varying degrees of prognostic un/certainty; parents with a child diagnosed with CF (n = 6), CF carrier status (n = 3) and those with the CFSPID designation (n = 7). The biographically disruptive nature of positive NBS results-regardless of immediate relevance to the child-dominated early experiences of positive results across all groups. For those with CF, biographical reparation involved becoming 'a CF family', underscoring biological kinship bonds and reinforcing familial identity. For those with uncertain results, biographical re-calibration was more complex. Diagnostic and prognostic uncertainty posed a barrier to entry for both the 'CF world' and the 'healthy kid' world, leading parents to attempt to minimise its role, either through rejection, or re-interpretation of their child's result. Other parents, however, experienced biographical reparation more dynamically. The concept of 'genetic nomadism' captures accounts of oscillation between the two worlds; movements that were responsive to evolving health experiences, as well as social, environmental and temporal factors. Through the concept of genetic nomadism, this paper delineates both the productive, as well as divisive, nature of uncertainty for biographical reparation in the aftermath of NBS, as well as the strategies parents use to harness it, in order to successfully navigate the world with a child with an ambiguous genetic future.

Exploring trust in (bio)medical and experiential knowledge of birth: The perspectives of pregnant women, new mothers and maternity care providers.

OBJECTIVE: To explore women's and maternity care providers' experiences of birth, and the roles of (bio)medical and experiential knowledge therein. RESEARCH DESIGN/SETTING: In-depth qualitative interviews were undertaken with pregnant women and new mothers (n = 14) as well as with a range of maternity care providers working for the National Health Service (n = 6) and privately (n = 7). FINDINGS: Trust emerged as a key concept in women's and maternity care providers' narratives. It was found that women and maternity care providers placed trust in two key areas: trust in past experiences and trust in women's innate abilities and embodied knowledge of birth. KEY CONCLUSIONS: Women and maternity care providers trust and utilise both (bio)medical and experiential forms of knowledge of birth in complex ways and the value an individual ascribes to (bio)medical and/or experiential knowledge is highly subjective, and not necessarily mutually exclusive. This destabilises the notion that (bio)medical knowledge is associated with experts and experiential knowledge is associated with 'lay' people, and that these two bodies of knowledge are distinct. IMPLICATIONS FOR PRACTICE: Trust is a key concept in maternity care. The predominance of biomedical models of birth risk reducing trust in the value of experiential based birth knowledges - both embodied and empathetic. Trust in experiential knowledge could help to facilitate woman-centred care by recognising women as valuable 'knowers' with unique insight to contribute, and not just receivers of medical knowledge. It may also help providers 'tune-in' with the women in their care if they allow their experiential knowledge to complement their (bio)medical knowledge.

What is a 'serious' genetic condition? The perceptions of people living with genetic conditions.

Despite no consensus on the definition of 'seriousness', the concept is regularly used in policy and practice contexts to categorise conditions, determine access to genetic technologies and uses of selective pregnancy termination. Whilst attempts have been made to create taxonomies of genetic condition seriousness to inform clinical and policy decision-making, these have often relied on condition appraisals made by health and genetics professionals. The views of people with genetic conditions have been largely under-represented. This study explores the concept of seriousness through the perspectives of people with a range of 'clinically serious' conditions (fragile X conditions, spinal muscular atrophy, cystic fibrosis, haemophilia, thalassaemia). Attitudes towards suffering, quality of life (QoL) and selective pregnancy termination were elucidated from 45 in-depth qualitative interviews and 469 postal/online surveys. The majority of participants reported good health/wellbeing, and the capacity for good QoL, despite experiencing suffering with their condition. Notably, participants with later-onset conditions held more negative views of their health and QoL, and were more likely to view their condition as an illness, than those with early-onset conditions. These participants were more likely to see their condition as part of their identity. Whilst most participants supported prenatal screening, there was little support for selective termination. Moreover, social environment emerged as a critical mediator of the experience of the condition. The complex and rich insights of people living with genetic conditions might usefully be incorporated into future genetic taxonomies of 'seriousness' to ensure they more accurately reflect the lived reality of those with genetic conditions.

Enabling women to access preferred methods of contraception: a rapid review and behavioural analysis.

BACKGROUND: Many pregnancies in the UK are either unplanned or ambivalent. This review aimed to (i) explore barriers and facilitators to women choosing and accessing a preferred method of contraception in the United Kingdom, and (ii) identify opportunities for behavioural interventions based on examination of interventions that are currently available nationally. METHODS: Three databases were searched, and experts contacted to identify grey literature for studies presenting barriers and facilitators to women choosing and accessing a preferred method of contraception, conducted in the UK and published between 2009 and October 2019. Information on barriers and facilitators were coded into overarching themes, which were then coded into Mechanisms of Actions (MoAs) as listed in the Theory and Techniques Tool. National interventions were identified by consulting stakeholders and coded into the Behaviour Change Wheel. The match between barriers/facilitators and intervention content was assessed using the Behaviour Change Wheel. RESULTS: We included 32 studies and identified 46 barrier and facilitator themes. The most cited MoA was Environmental Context and Resources, which primarily related to the services women had access to and care they received. Social Influences, Beliefs about Consequences (e.g., side effects) and Knowledge were also key. The behavioural analysis highlighted four priority intervention functions (Modelling, Enablement, Education and Environmental Restructuring) that can be targeted to support women to choose and access their preferred method of contraception. Relevant policy categories and behaviour change techniques are also highlighted. CONCLUSIONS: This review highlights factors that influence women's choices and access to contraception and recommends opportunities that may be targeted for future interventions in order to support women to access preferred contraception. REGISTRATION: Protocol was registered with PROSPERO (an international database of prospectively registered systematic reviews in health and social care) in December 2019, CRD42019161156 .

Absorbing it all: A meta-ethnography of parents' unfolding experiences of newborn screening.

In a context of increasing international dialogue around the appropriate means and ends of newborn screening programmes, it is critical to explore the perspectives of those directly impacted by such screening. This meta-ethnography uses a systematic review process to identify qualitative studies that focus on parents' experiences of newborn screening published in English-language academic journals from 2000 to 2019 (n = 36). The included studies represent a range of moments, outcomes, and conditions that illuminate discrete elements of the newborn screening journey. We draw on these varied studies to construct a diagram of possible newborn screening pathways and through so-doing identify a critical window of time between the signalling of a positive newborn screen and the end of the screening process. During this critical window of time, families navigate complex emotional reactions, information, and decisions. From an in-depth analysis of this data, we develop the concept of "absorptive capacity" as a lens through which to understand parents' responses to new and emerging information. Alongside this, we identify how the "concertinaing of time" - the various ways that parents experience the expansion and compression of time throughout and beyond the screening pathway - affects their absorptive capacities. This study underscores the need to move away from viewing newborn screening as a discrete series of clinical events and instead understand it as a process that can have far-reaching implications across time, space, and family groups. Using this understanding of screening as a starting point, we make recommendations to facilitate communication and support for screened families, including the antenatal provision of information to parents and accommodations for the fluctuations in parents' absorptive capacities across the screening trajectory.

Children's perspectives and experiences of health, diet, physical activity and weight in an urban, multi-ethnic UK population: A qualitative study.

BACKGROUND: Children from Black and South Asian ethnic groups are at risk for childhood obesity in the United Kingdom. To inform local action for childhood obesity prevention, it is crucial to explore the basis of ethnic disparities and consider the perspectives of children. This study aimed to understand cultural and contextual factors influencing childhood obesity in an ethnically diverse population using child-centred methodology. METHODS: 'Draw, write and tell' interviews were held with children aged 9-10 years in Coventry, an urban, multi-ethnic city in the United Kingdom. Data were analysed thematically using framework analysis. RESULTS: Twenty-six children participated (85% from Black or minority ethnic groups). Children's perspectives revealed universal themes around health, diet, physical activity and weight and highlighted issues specific to ethnic groups and those living in deprived areas. An underlying feature was weight-based stigmatization and group stereotyping, and an emphasis on internal factors as the cause of obesity. Children described some experiences of social disadvantage but did not regard these as a barrier to being physically active. Children identified cultural or religious practices or experiences of migration that influenced diet and physical activity. CONCLUSIONS: These findings allow a broad range of children's perspectives to inform future intervention design. In addition, the study was able to identify the many similarities and small amount of diversity in children's perspectives across ethnic groups.

Attitudes toward population screening among people living with fragile X syndrome in the UK: 'I wouldn't wish him away, I'd just wish his fragile X syndrome away'.

In an age of expanded genetic screening, fragile X syndrome is increasingly considered a candidate condition, given its prevalence, the absence of curative interventions, and its impact on families. However, relatively little research has explored the views of families and people living with fragile X syndrome toward population screening. This study reports on in-depth interviews with 19 participants: 3 with people diagnosed with a fragile X condition (fragile X syndrome = 2, FXTAS = 1) and 16 people with fragile X syndrome in their family (11 parents, 2 grandparents, 1 spouse, 1 sibling, and 1 aunt) living in the UK. This study reveals the complexity of attitudes within this group and the existence of genuine ambivalence toward different population screening programs. While the overwhelming majority believed that preconception and newborn genetic screening should be made available to the general public, the notion of prenatal screening was far more controversial, with only five participants expressing support for such a program. Expressivist concerns were highlighted equally both by those who supported prenatal screening, as by also those who did not. Participants who supported prenatal screening drew clear distinctions between people with fragile X syndrome and the condition itself, in order to neutralize expressivist concerns and existential threat. However, for others, this division was challenging to maintain. Impairment effects associated with fragile X syndrome, more specifically, its implications for behavior, intellect, and personality, made it harder for some participants to conceptually separate the person from their condition. This study concludes that screening remains a complex issue for families living with genetic conditions and that expressivist concerns affect, and are managed by, families living with different types of disability in contrasting ways. Screening for conditions that affect personality, behavior, and intellect produces unique iterations of expressivism, identity, and stigmatization that families produce specific, and creative, strategies to navigate.

Which types of conditions should be included in reproductive genetic carrier screening? Views of parents of children with a genetic condition.

Reproductive genetic carrier screening identifies couples with an increased chance of having children with autosomal and X-linked recessive conditions. Initially only offered for single conditions to people with a high priori risk, carrier screening is becoming increasingly offered to individuals/couples in the general population for a wider range of genetic conditions. Despite advances in genomic testing technology and greater availability of carrier screening panels, there is no consensus around which types of conditions to include in carrier screening panels. This study sought to identify which types of conditions parents of children with a genetic condition believe should be included in carrier screening. Participants (n = 150) were recruited through Royal Children's Hospital (RCH) Melbourne outpatient clinics, the Genetic Support Network of Victoria (GSNV) and a databank of children with hearing loss (VicCHILD). This study found that the majority of participants support offering carrier screening for: neuromuscular conditions (n = 128/134, 95.5%), early fatal neurodegenerative conditions (n = 130/141, 92.2%), chronic multi-system disorders (n = 124/135, 91.9%), conditions which cause intellectual disability (n = 128/139, 92.1%) and treatable metabolic conditions (n = 120/138, 87.0%). Views towards the inclusion of non-syndromic hearing loss (n = 88/135, 65.2%) and preventable adult-onset conditions (n = 75/135, 55.6%) were more mixed. Most participants indicated that they would use reproductive options to avoid having a child with the more clinically severe conditions, but most would not do so for clinically milder conditions. A recurring association was observed between participants' views towards carrier screening and their lived experience of having a child with a genetic condition.

Social and cultural influences on genetic screening programme acceptability: A mixed-methods study of the views of adults, carriers, and family members living with thalassemia in the UK.

As population-level carrier screening panels for reprogenetic information emerge globally, conditions to be included, and the timing of implementation is widely debated. Thalassemia is the only condition for which population-based prenatal carrier screening is offered in the UK. However, little is known about the views and experiences of the UK thalassemia-affected community toward this screening or other forms of genetic screening for thalassemia (newborn, preconception), despite the range of direct consequences of screening programmes for this group. Using a mixed-methods integrative analysis (qualitative interviews n = 20 and quantitative survey n = 80), this study outlines the experiences and attitudes of adults with thalassemia, their family members, and screen-identified thalassemia carriers toward preconception, prenatal, and newborn screening for thalassemia. The majority of participants described thalassemia as a burdensome condition with a range of negative impacts, which contributed to their strong support for screening in all its potential formats. However, the data also highlight the challenges of each screening mode for this group, reflected in the high level of value conflict in participants' accounts and decisions. Cultural, social, and (to a lesser extent) religious factors were found to mitigate against the advantages of early screens, particularly within faith communities. Social stigma emerged as key to this process, informing the way that thalassemia severity was not only perceived, but also experienced by affected adults, which ultimately influenced screening uptake and outcomes. These findings suggest that cultural and social sensitivity is as important as the mode of screening delivery itself, if the iatrogenic and unintended harms of screening-particularly the social/psychological burden of value conflict-are to be adequately addressed and minimized.