Healthcare Professionals’ Views on Expanding Newborn Screening with or without Genomics in France: Results of the SeDeN-p2 Study

Healthcare Professionals’ Views on Expanding Newborn Screening with or without Genomics in France: Results of the SeDeN-p2 Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Healthcare Professionals’ Views on Expanding Newborn Screening with or without Genomics in France: Results of the SeDeN-p2 Study Camille Level, Frédéric Huet, Dominique Salvi, Christel Thauvin-Robinet, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8743981/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 9 You are reading this latest preprint version Abstract Background Therapeutic advances and the rapid, cost-effective development of next-generation sequencing (NGS) have increased interest in expanding newborn screening (NBS) through genomics. The SeDeN-p2 study assessed the acceptability among healthcare professionals in France, of expanding NBS, particularly through the use of genetics as a first-line test, by examining areas of convergence and divergence in their expectations. Methods A national cross-sectional survey was conducted between June and December 2021 via professional networks and learned societies involved in NBS and genetics, in partnership with the French Society of Newborn Screening. The questionnaire comprised 101 closed-ended and 14 open-ended questions. After data cleaning, 1,077 responses were analysed. Results Respondents were mainly paediatricians (44%), gynaecologists or midwives (38%), and medical geneticists (18%). There was near-unanimous support for including treatable childhood disorders, with over 95% endorsing their integration into NBS, although 29% still considered the current NBS programme sufficient. Views varied substantially by specialty, particularly regarding the scope of conditions and the use of NGS. Genetics professionals were more conservative, especially concerning variants with limited actionability, organisational constraints, and interpretive uncertainty, while midwives and gynaecologists were generally more favourable. Convergence was strongest for treatable paediatric disorders and shared ethical concerns, notably data misuse, psychosocial burden, and the child’s future autonomy. The need for improved communication with families was widely emphasised. Conclusion The SeDeN-p2 study shows strong but conditional support among French healthcare professionals for integrating genetics into NBS, providing key insights to inform future policy and practice. Scientific community and society/Social sciences/Economics Health sciences/Health care/Paediatrics Expanded newborn screening Genomic sequencing Professional acceptability Quantitative studies Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Newborn screening (NBS) is a major public health programme enabling early detection and treatment of severe congenital disorders. Traditionally based on biochemical assays targeting a limited number of conditions, it has evolved alongside scientific and technological advances. The development of next-generation sequencing (NGS), declining genomic costs, and increasing therapeutic options for rare diseases have renewed interest in expanding screening 1 – 6 . These developments have raised international debates on the responsible integration of genomic approaches into public health and on which conditions should be included. In the late 2010s, initiatives such as the BabySeq Project in the United States helped structure these discussions. At that time, French NBS remained limited to severe childhood-onset conditions, mainly identified through biochemical testing, with genetics used as a second-tier tool. Meanwhile, no structured national assessment of healthcare professionals’ views on genomic NBS (gNBS) was available. Recent revisions of French bioethics laws have since created a more favourable framework for innovation 7 , 8 . In this context, the Fédération Hospitalo-Universitaire TRANSLAD launched the SeDeN project ( Séquençage et Dépistage Néonatal ) to examine expectations and barriers related to NBS expansion, including genomic approaches. The project comprises several components: policy analysis (SeDeN-p1), healthcare professionals (SeDeN-p2), parents (SeDeN-p3), and policymakers and stakeholders (SeDeN-p4) (Supplemental Figure S1 ). This article reports findings from SeDeN-p2. The study assessed how healthcare professionals involved in perinatal care and genetics in France perceive potential NBS expansion, with and without first-line genetic testing. It aimed to measure levels of acceptability across types of conditions and to identify areas of consensus, divergence, and perceived ethical, organisational, and informational constraints. Methods The SeDeN-p2 study employed a nationwide survey-based methodology designed to capture a wide range of opinions from HCPs in France on the topic of expanding NBS, including genetic technologies. SeDeN-p2 consisted of an exploratory qualitative phase aimed at assisting in the design of a questionnaire aligned with field-related concerns, followed by a quantitative investigative phase based on a self-administered survey. The preliminary interviews were conducted in accordance with the COREQ guidelines. A purposive sample was selected to ensure variation in professional background, practice setting, and involvement in perinatal care. Fifteen participants were interviewed, including obstetricians, paediatricians, midwives, biologists, clinical geneticists, and public policymakers. Semi-structured interviews were conducted online by CL between November 2020 and April 2021, audio-recorded, transcribed, and anonymised. Interviews lasted on average 1 hour and 33 minutes and were analysed using thematic analysis supported by NVivo software (version 12 Pro). This exploratory qualitative phase was used to refine the content of a nationwide online questionnaire. It led to the identification of four key domains: (i) criteria for selecting conditions for NBS; (ii) scope of conditions and types of results to be reported; (iii) attitudes toward the integration of NGS into NBS; and (iv) expectations and practices regarding parental information and consent. These findings informed the questionnaire design to ensure alignment with the diversity and coherence of professional perspectives. Accordingly, the questionnaire was constructed as a four-module questionnaire, each module corresponding to one of these domains and addressing: (i) criteria guiding condition selection, (ii) scope of genetic findings, (iii) views on NGS integration, and (iv) information practices. Because completion rates differed across modules, the number of responses included in the analyses varied by module. A module-based analytical strategy was therefore defined a priori : analyses were conducted separately within each thematic block, prioritising interpretative coherence over maximising a single overall sample size. Detailed descriptions of the questionnaire content, response scales, and analytical procedures, including inclusion thresholds and comparability checks, are provided in the Supplemental Methods S1 and Supplemental Figure S2. The survey was administered online between June and December 2021. It was disseminated nationwide through professional networks and learned societies representing paediatricians, medical geneticists, genetic counsellors, gynaecologists, and midwives. Dissemination relied on professional mailing lists and, for several learned societies, publication of the survey link on their official websites. Participation was voluntary and not accompanied by any financial reward. All participants were invited to provide informed consent for the processing of data in accordance with the research protocol. Analyses were primarily descriptive and comparative across questionnaire modules. Categorical variables were summarised as counts and percentages within each module-specific analytical subsample. Missing data were reported explicitly and were not imputed. Comparisons across subgroups, including professional specialties were mainly based on observed differences in proportions and interpreted descriptively. Qualitative open text responses were used illustratively to enrich the interpretation of quantitative results. Items assessing opinions on categories of genetic findings or NGS-related statements were displayed in two-dimensional “landscape” plots using R via Rstudio (version 4.4.2.), showing for each item (i) overall agreement, (ii) variability across specialties and (iii) the min–max range of specialty-specific responses. In addition, for a limited number of key outcomes, namely the prioritisation of screening criteria and the overall position on NGS integration, exploratory global tests of association with professional specialty were conducted. Given small expected cell counts in several contingency tables, Fisher’s exact test was used when appropriate. Results Sociodemographic and professional characteristics Across all modules, respondents covered a wide range of medical specialties and practice settings. Paediatricians represented the largest professional group, accounting for approximately 43–44% of respondents across modules, while midwives constituted the second largest group, representing around 20–24%. These were followed by medical geneticists, gynaecologists and genetic counsellors. Approximately half of the respondents worked in university hospitals, and around one third reported complementary academic activities, including teaching or research. Most participants were mid-career (43–44%) or senior (34%) professionals, and the majority reported regular involvement in NBS activities. Engagement with genetics-related practices was common: more than half reported direct experience with patients affected by rare diseases, and over three quarters reported experience with genetic testing. The sample was predominantly female, with respondents distributed across age groups and family situations. A detailed description of sociodemographic and professional characteristics for each module-specific analytical sample is provided in Supplemental Table S1 . Criteria for NBS module In this section (N = 1,077), all the proposed criteria for assessing NBS were rated as important, although differences emerged in the level of importance attributed to each (Fig. 1 ). Criteria directly related to expected clinical benefits, including the superiority of early treatment outcomes, the test ability to detect the condition at an early stage, test performance, and test acceptability, received near-unanimous support (83–87% “Very important”). In contrast, criteria related to economic considerations or organisational flexibility, such as cost-effectiveness or the possibility of repeating the test, were more frequently rated as of secondary importance (resp. 35% and 23% “Very important”). Among the Andermann criteria, equity and access to screening for the entire target population was the most strongly supported (94% “Very important”). Across Wilson and Jungner, and Andermann frameworks, respondents consistently agreed that the expected benefits should outweigh the potential harms (84–89% “Very important”). When asked to prioritize, respondents selected the superiority of early treatment outcomes as the single most important criterion for 59%, compared with disease severity (12%) or early detection (8%) (Supplemental Figure S3). Conversely, the possibility of repeating the test and cost considerations were most frequently identified as the least important criteria (resp. 30% and 36%), further illustrating the predominance of clinical benefit over economic or organisational aspects in respondents’ judgments. Prioritisation patterns differed according to professional specialty, experience with genetics, practice setting, and sociodemographic characteristics. Overall, specialty and genetic expertise showed the most consistent associations with governance-, evaluation-, and safeguard-related criteria, whereas frontline and non-university settings were more frequently associated with criteria emphasising population relevance and implementation feasibility. Detailed cross-tabulations and statistical associations are provided in the Supplemental Analysis S1. When invited to suggest additional criteria they considered important for deciding whether a condition should be included in NBS, a small proportion of respondents (n = 67; 6.7%) provided open-ended comments. Most of these responses did not introduce entirely new criteria, but rather reiterated or specified dimensions already captured by existing frameworks. Respondents most frequently emphasised the availability of effective treatment and the potential for early intervention to modify morbidity or mortality, often stressing that direct benefit to the child should prevail over considerations of prevalence or cost. Other comments referred to disease severity, expected quality-of-life gains, and the balance between psychological and clinical burden. Ethical considerations were also raised, including consent shortly after birth, parental decision-making on behalf of the child, and the need for adequate information and psychological support. Genetic findings module In the genetic findings module (N = 874), 44% of respondents considered the current scope of NBS in France insufficient, 29% judged it adequate, and 27% expressed no opinion. Strong agreement was reported for childhood-onset conditions with curative potential (76% strongly agree; 19% somewhat agree) and for conditions in which early intervention could improve prognosis (83% strongly agree; 15% somewhat agree). Agreement remained high, though less unanimous when the benefit applied only in adulthood, however 72–82% strongly agree/somewhat agree, and when genetic findings offered only indirect or delayed benefits, such as pharmacogenetic information (66% strongly agree/somewhat agree). By contrast, findings without direct medical benefit for the child received limited support, including information primarily relevant for relatives (31% strongly agree/somewhat agree), carrier status (30% strongly agree/somewhat agree), and variants of uncertain significance (12% strongly agree/somewhat agree) (Supplemental Figure S4). Response patterns varied across professional profiles (differences by specialty are shown in Fig. 2 ; additional cross-analyses are reported in the Supplemental Analysis S1). Medical geneticists and genetic counsellors consistently appeared as the least favourable profiles overall, except for childhood-onset conditions with clear clinical actionability (all p < 0.001). In contrast, midwives and gynaecologists were among the most favourable groups across a broad range of genetic findings, contributing to higher overall agreement rates, particularly for childhood actionable categories (p < 0.05), adult-onset actionable variants (p < 0.05), and information relevant for relatives (p < 0.01). Paediatricians occupied an intermediate position, generally slightly less supportive than the overall mean, with significant associations observed for childhood non-actionable findings (p < 0.01) and adult-onset variants (p < 0.05), but less systematic differences across other categories. Greater exposure to genetics and academic involvement were associated with more cautious positions, especially for adult-onset non-actionable variants, carrier status, and variants of uncertain significance, whereas professionals in private or mixed practice tended to express broader support. Younger respondents were generally more favourable to wider disclosure, while more senior professionals adopted more restrictive positions. NGS Module Regarding possible modalities for integrating NGS into NBS (N = 751), only one third of respondents reported being unable to take a position, mainly because they did not consider the issue within their field of expertise; a small additional fraction expressed no opinion. Overall, 52.2% supported a limited panel, 2.9% endorsed exome or genome sequencing, and 10.4% favoured avoiding NGS altogether. Positions differed significantly across specialties (p < 0.001), highlighting marked heterogeneity (Fig. 3 A). For technical items (Fig. 3 B), such as whether NGS produces too many false positives or negatives, whether it would be more efficient than current techniques, or whether sufficient evidence of technical performance or benefit–risk balance exists, “Not my field of expertise” was frequently selected (44–50%). Among those expressing an opinion, no clear majority emerged. Organisational items elicited more definite positions, although statements regarding operational feasibility, long-term cost–benefit balance, or turnaround times still showed high levels of self-reported lack of expertise (44–51%). By contrast, items related to professional roles and system organisation generated clearer agreement: 58.4% supported mandatory genetics consultation (25.6% strongly, 32.8% somewhat), and 57.7% agreed that health professionals are insufficiently trained in genetics (20.6% strongly, 37.1% somewhat). Ethical and societal items were less polarised but largely supported. About 70% agreed that NGS would raise ethical issues (20.2% strongly, 49.6% somewhat). Concerns about data misuse (62.2%), future child autonomy (57.6%), family anxiety (62.9%), and anxiety related to adult-onset risk (65.6%) were also frequently endorsed. Agreement patterns differed sharply across specialties across all domains (Supplemental Figure S5). Technical and organisational items showed particularly strong structuring effects: operational feasibility, turnaround times, insufficient training, and difficulties limiting returned information were strongly associated with specialty and genetic exposure (all p < 0.001). Geneticists and genetic counsellors expressed the highest levels of concern, whereas midwives and, to a lesser extent, gynaecologists were less likely to endorse these limitations. For technical performance, genetic specialists were more favourable overall but more explicit about current limitations. Items related to family experience and psychosocial impact showed a distinct pattern. Higher levels of agreement with statements emphasising anxiety for families or potential psychosocial burden were observed among paediatricians and genetic counsellors, with significant associations according to specialty, parenthood, and age (all p < 0.01). Medical geneticists, by contrast, expressed lower levels of agreement with these items, indicating a relative distancing from psychosocial considerations compared with perinatal and counselling-oriented profiles. Broader ethical and societal concerns including data misuse, ethical complexity, and child autonomy, were strongly associated with specialty, genetic expertise, and practice setting (most p < 0.001). Genetic counsellors, and for several items paediatricians, more frequently endorsed these concerns, whereas midwives and gynaecologists were less likely to prioritise them. These patterns indicate stronger alignment of genomics-oriented and child-centred profiles with ethical boundary-setting, particularly when long-term or societal implications are foregrounded. When asked how parents might react to the integration of NGS into NBS (Supplemental Figure S6), respondents most often anticipated questioning attitudes (53%), followed by anxiety (29%) and confidence (19%). Differences by specialties were less pronounced, although medical geneticists more often anticipated confidence, paediatricians more often anxiety, and genetic counsellors questioning attitudes. Regarding parental expectations, 59% anticipated divided parental positions, 30% active demand, 8% reluctance, and 4% indifference. Qualitative comments (71 on organisational impact, 66 on technical issues, 82 on family impact) reiterated the necessity of comprehensive planning before implementation. Many emphasized that current infrastructures, particularly in non-specialized settings, would be strained by widespread adoption of NGS in NBS. Participants voiced concerns over result interpretation, risk of incidental findings, and the burden of VUS. Ethical apprehensions centred on informed consent, the preservation of child autonomy, and the appropriate return of uncertain results. Family Information module Respondents (N = 751) were also asked about the timing, content, and format of parental information on NBS. Most considered current information insufficient: over two thirds rated it as “moderate” (37%) or “low” (32%) (Fig. 4 A), and 62% believed parents are rarely aware that NBS is not mandatory (Fig. 4 B). Differences by specialty were marked: geneticists and genetic counsellors were the most critical, whereas midwives reported more favourable assessments for both questions. The survey also revealed a broad perception of insufficient professional training in relation to NGS among respondents included in the NGS module. When asked “ With your current knowledge, how prepared do you feel to understand potential results from next-generation sequencing? ” (Fig. 4 C), fewer than 13% of respondents considered themselves ‘perfectly’ trained, mainly medical geneticists and genetic counsellors. When invited to consider a second question - ‘ If NGS were integrated into newborn screening, how prepared would you feel to discuss these results and answer parents’ questions? ’ (Fig. 4 D) - fewer than 7% reported feeling fully able to do so. Across both items, 60–70% rated themselves poorly or very poorly trained, with a marked drop between technical understanding and communicative readiness. Differences by specialty were substantial: medical geneticists reported the highest confidence, while perinatal professionals, especially midwives, reported the lowest, with over 90% considering their training insufficient. Additional analyses by practice setting and sociodemographic characteristics are presented in the Supplemental Analysis S1. Regarding timing, respondents favoured late pregnancy (third trimester, 68%) and the first three postnatal days (79%), whereas preconception (10%) and first trimester (12%) were rarely endorsed. Direct discussion with a health professional was overwhelmingly preferred (94%), followed by written materials (77%), while digital tools and group sessions were less frequently selected (both 32%). In terms of content, respondents prioritised information on screened diseases (78%), treatment or management options (60%), and health impact (53%). False positives and negatives were also considered important (48%), whereas sample storage (6%) and research use (5%) were seldom prioritised (Table 1 ). Table 1 Professionals’ views on the timing, modalities, and content of parental information regarding NBS (N = 751) This table summarizes professionals’ views on the preferred timing, modalities, and content of information provided to parents about NBS, including when information should be delivered, how it should be communicated, and which topics should be prioritized. Results are reported as absolute numbers, with percentages shown in parentheses. Because these items were assessed using multiple-choice questions, respondents could select more than one option. As a result, percentages may sum to more than 100%. Percentages are calculated based on the total number of respondents (N = 751). n (%) The moment(s) you consider the most appropriate to explain NBS to families 1. Before pregnancy (birth planning, desire for children, etc.) / Preconceptional period 76 (10%) 2. At the beginning of pregnancy (1st trimester) 89 (12%) 3. In the middle of pregnancy (2nd trimester) 194 (26%) 4. At the end of pregnancy (3rd trimester) 507 (68%) 5. Upon arrival at the maternity ward / At childbirth 56 (7.5%) 6. Within 3 days after childbirth / Postnatal (within 3 days) 594 (79%) The way(s) you consider effective to inform parents about NBS before testing 1. Discussion with a healthcare professional 705 (94%) 2. A leaflet or brochure / Educational booklet 582 (77%) 3. A website / Digital modalities (internet, mobile app, etc.) 238 (32%) 4. An information meeting (e.g., at the maternity ward) / Group information 244 (32%) 5. Other 4 (0.5%) The information you consider essential to be given 1. The names of the diseases included in the screening 584 (78%) 2. The possible effects of the detected diseases on my baby’s health / The impact of each condition on the child’s health 398 (53%) 3. The number of babies born with these diseases each year / The prevalence of conditions 222 (30%) 4. The possibilities for treatment/management if my baby is sick / What can be done to manage the child if diagnosed 451 (60%) 5. The risk of false positives and false negatives 361 (48%) 6. Storage of dried blood spots (duration, possible reanalysis, etc.) 47 (6.3%) 7. If dried blood spots are used for research 38 (5.1%) 8. Other 19 (2.5%) Discussion The SeDeN-p2 study provides a large-scale national assessment of HCPs’ perspectives on the expansion of NBS in France, including genomic integration. By surveying the largest and most diverse sample of perinatal professionals studied to date across an entire country, including overseas territories, it addresses a gap identified in previous literature, which was generally limited in size, scope, or specialty representation (Table 2 ) 9 – 18 . It is the only study to include gynaecologists and midwives at this scale, although they are central to NBS delivery in maternity settings. Its quantitative design, informed by prior qualitative work and complemented by open-ended responses, also allows comparison across professional groups. Table 2 Summary of Selected International Studies on Professional Acceptability of gNBS This table presents a non-exhaustive overview of selected international studies examining healthcare professionals’ acceptability of gNBS, including their methodological characteristics, study populations, and key findings. Reference Country Methodology Population Key Findings Ulm et al., 2015 USA Exploratory cross-sectional electronic survey of ACMG members 113 genetic professionals Most respondents considered that whole-genome sequencing should not currently be used in NBS and should not be mandatory if implemented. Nevertheless, many anticipated GS as a future application. Support was conditional on accurate interpretation, extended consent processes, comprehensive genetic counselling, and comparable costs and turnaround times to existing NBS. Participants endorsed current criteria for inclusion of conditions and expressed reservations about integrating GS into traditional NBS without revisiting these criteria. Iskrov et al., 2017 Bulgaria Quantitative study based on a questionnaire 120 paediatricians and geneticists Paediatricians were more supportive of population-based GS than geneticists, who expressed stronger reservations. Both groups highlighted ethical concerns, the need for strict data protection, and the importance of genetic counselling and psychological support. While non-selective GS was largely considered infeasible, selective GS was viewed as a potentially valuable complement to existing NBS programs. Pereira et al., 2019 USA Quantitative survey combining closed-ended questions and open-ended responses 144 paediatricians (and 493 parents of infants enrolled in the BabySeq project) Both parents and clinicians perceived greater risks associated with GS than with conventional NBS. Parents nevertheless anticipated more benefits and fewer risks than clinicians. Clinicians expressed stronger concerns regarding privacy and discrimination, whereas parents emphasized potential benefits extending beyond immediate clinical utility. van Dijk et al., 2021 Netherlands Qualitative study based on semi-structured interviews 22 professionals HCPs, test developers, policy makers (and 17 parents of children with normal or abnormal NBS results) Participants generally supported expanding NBS when restricted to treatable conditions. Concerns focused on uncertain findings, untreatable disorders, and the complexity of informed consent. Two contrasting perspectives emerged: a targeted-scope approach prioritising neonatal health benefits with limited parental choice, and a broader-scope approach emphasising wider benefits, reproductive planning, and parental autonomy. Policymakers were seen as needing to balance these perspectives in future NBS decisions. Andrews et al., 2022 USA Mixed-methods stakeholder engagement study combining a pre-panel survey and rapid qualitative analysis of multi-stakeholder panel discussions 42 expert stakeholders from the United States and Canada representing multiple NBS stakeholder groups Stakeholders identified major structural and organisational barriers to NBS modernization, notably insufficient data for decision-making, laboratory capacity constraints, and lengthy state-level implementation timelines. Discussions emphasised infant well-being as the core objective of NBS, while highlighting tensions between the accelerating pipeline of transformative therapies and the limited capacity of existing systems. Modernization was framed as a collective governance challenge requiring evidence-based decisions, increased funding, enhanced coordination, and novel oversight models rather than technological change alone. Wu et al., 2022 China Quantitative questionnaire-based study 258 healthcare professionals from 43 Chinese NBS centres (18% clinicians; 82% laboratory, blood collection, or management staff) Most respondents expressed interest in gNBS (≈ 81%) and considered it necessary in the Chinese context (≈ 98%). Participants largely believed gNBS could expand the range of screened conditions (≈ 90%), while substantial concerns were raised about the limited availability of genetic counselling (≈ 73%) and ethical implications. More than half (≈ 55%) supported a combined approach integrating gNBS with tandem mass spectrometry. Cao et al., 2023 Autralia Qualitative study based on semi-structured interviews 16 healthcare professionals with clinical or policy experience in NBS and/or next-generation sequencing Participants generally considered GS not yet appropriate for routine NBS, although most anticipated its introduction within the next decade. Views diverged regarding eligible conditions and data governance. The need for further research and the central role of genetic counsellors in education, consent, and result disclosure was consistently emphasised. White et al., 2023 Australia Online cross-sectional survey 145 healthcare professionals (and 163 parents) Most healthcare professionals (62%) considered GS premature for current NBS, despite anticipating its use in the near future. Both groups highlighted critical prerequisites, including reliable data interpretation, pre- and post-test counselling, and robust information, consent, and opt-out processes. Overall support was cautious and conditional, emphasising ethical, social, legal, and organisational readiness. Bayrak et al., 2024 Turkey Cross-sectional descriptive questionnaire study with quantitative analysis 147 healthcare professionals involved in heel prick screening Respondents demonstrated strong knowledge of technical aspects of sample collection, storage, and transport, but notable gaps regarding congenital metabolic diseases, their clinical manifestations, and referral pathways. Knowledge levels varied significantly across occupational groups. Although the study did not address genomic screening directly, it highlights how uneven frontline knowledge may constitute a structural constraint for the effective implementation or extension of NBS programs. Scarfe et al., 2025 Australia Qualitative study using semi-structured interviews and small group discussions with inductive content analysis 19 healthcare professionals and scientists involved in NBS, and 16 policy-makers responsible for program delivery and governance Participants acknowledged the potential of genomics to improve early detection and diagnosis, but more frequently stressed technical, organisational, and system-level risks. Divergent views emerged on whether gNBS should remain aligned with the current paradigm focused on severe, treatable, early-onset conditions, or justify a broader paradigm shift extending benefits beyond the neonatal period. Effective implementation was considered conditional on system readiness, including national coordination, appropriate consent models, agreed approaches to uncertain results, workforce capacity, infrastructure, and clear ethical and legal frameworks. HCP: Healthcare professionals A strong consensus emerged around the clinical foundations of NBS expansion. Actionable childhood diseases with clear clinical pathways and demonstrable benefit from early intervention were overwhelmingly supported, and principles such as equity of access and benefit–harm balance remained central. Economic and organisational considerations were consistently secondary. These patterns confirm the enduring structuring role of the Wilson & Jungner and Andermann frameworks, reflected in the 2023 HAS criteria 19 . Genomic technologies, however, introduce a qualitative shift. By enabling multiple diseases to be screened through a single test, NGS may loosen historical technical constraints and therefore challenge how these criteria are operationalised. The debate no longer concerns only which conditions meet established principles, but also how broadly those principles should be interpreted in a genomic context. In our results, this shift translated into a graded hierarchy of acceptability: strong support for actionable childhood conditions; more conditional support for adult-onset or indirectly beneficial findings; and reluctance toward non-actionable or uncertain variants. Concerns about child autonomy, VUS, and long-term implications underscore the difficulty of defining acceptable limits in a genomic context. Within this reconfigured landscape, two professional orientations became visible. One, more frequently associated with perinatal and frontline clinical practice, emphasised feasibility and immediate clinical utility, while also supporting broader disclosure when findings contribute to care pathways, intervention, or family-related benefit. The other, more closely linked to genetic and academic expertise, placed stronger emphasis on analytic validity, governance safeguards, and interpretive robustness, favouring disclosure primarily when findings are clearly actionable and clinically reliable, and expressing greater caution toward variants with limited or uncertain utility. These tensions echo international debates on scope expansion, where arguments for broader inclusion often rely on the absence of alternative screening opportunities, potential reproductive counselling benefits, or reduction of diagnostic delay, while counterarguments are linked to the risks of disclosing late-onset or uncertain during the vulnerability of the neonatal period 20 . Staged or two-step strategies have been proposed as possible compromises between these positions. Beyond questions of scope, our findings also reveal systemic ambivalence toward genomic integration. Interest in diagnostic potential coexisted with concerns about the capacity to absorb and act upon large-scale genomic data for all newborns, including infrastructure limitations, insufficient specialised training, lack of standardised protocols, and the need for ethical alignment. These findings suggest that genomic expansion is not merely a technological shift but a systemic one, requiring reinforced training for paediatricians, midwives, gynaecologists and primary care physicians, investment in bioinformatics support, coordinated variant interpretation frameworks, and robust governance structures. Without such preparation, expansion may increase inequities and strain specific sectors of the healthcare system. The management of VUS emerged as particularly complex. While NBS professionals are accustomed to uncertainty in metabolic screening, where follow-up testing is available and benefits clearly outweigh harms, genomic expansion introduces uncertainty across a broader range of diseases, often without orthogonal confirmatory tests. In this setting, the benefit–harm balance becomes more difficult to establish. Many respondents viewed non-disclosure of VUS as a reasonable boundary condition for expansion, especially given expectations that interpretive precision may improve over time. Information practices appeared as a central condition of acceptability. Many professionals considered current parental information insufficient and reported limited preparedness to manage genomic results. While earlier and more structured communication was supported, fully individualised decision-making was viewed as difficult in routine settings. These findings reinforce calls for nationally coordinated information strategies in any genomic extension 21 . International research reports similar patterns, including stronger support for actionable childhood conditions, greater caution among genetic specialists, and concerns regarding counselling resources, consent, operational feasibility, and scope definition. Reviews synthesising these studies indicate that while gNBS is increasingly considered plausible, its legitimacy depends on balancing clinical utility, parental autonomy, and system capacity. When compared with parental perspectives, clinicians tend to express greater concern regarding privacy, discrimination, data governance, and long-term uncertainty, whereas parents more often emphasise potential benefit and reassurance 22 , 23 . Similar patterns were observed in the SeDeN-p3 study 20 . Several limitations must be acknowledged. Voluntary participation may have introduced selection bias, and findings should not be interpreted as reflecting national prevalence of opinions. The survey was conducted in 2021, when gNBS remained largely prospective; subsequent therapeutic advances pilot initiatives may have influenced professional views. Technical complexity and heterogeneous familiarity with genetics across professional groups likely contributed to self-reported limited expertise among many respondents, suggesting that some answers may reflect uncertainty rather than fixed positions. In particular, low support for exome or genome sequencing should be interpreted cautiously, as these terms may have been perceived as implying unrestricted analysis, rather than targeted approaches. Since data collection, several expanded NBS initiatives have moved into pilot or real-world research phases. Evidence emerging from these experiences, as synthesised in recent reviews 21 , 24 – 42 , will be essential to refine genomic screening strategies in practice. Parallel collaborative efforts, including the International Consortium on Newborn Sequencing (ICoNS) [URL can further support this professional learning process by enabling cross-site comparisons and deliberation on shared challenges such as gene list definition, consent models, data governance, and public health integration 43 – 49 . Updated lists of treatable rare genetic diseases are also being developed to inform policy and clinical decision-making and to provide a transparent basis for professional discussion, training, and guideline development 50 . Declarations Data Availability Statement The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. URL International Consortium on Newborn Sequencing (ICoNS) : https://www.iconseq.org/the-consortium Acknowledgements The authors thank all healthcare professionals who participated in the study and the professional networks that supported the dissemination of the survey. In this contex, they are particularly grateful to the Inter Filières de Santé Maladies Rares , the Association Francophone de Génétique Clinique , and the Société Française de Médecine Prédictive et Personnalisée for facilitating the distribution of the survey within their networks. The authors also acknowledge ADN Soft for their support in data management and analysis. Authors' contributions CL (Camille Level), LF (Laurence Faivre), ML (Margot Lemaitre), DS (Dominique Salvi), CTR (Christel Thauvin-Robinet), FH (Frédéric Huet), CP (Christine Peyron) CL conceived and designed the study, coordinated recruitment, supervised data management, conducted statistical and qualitative analyses, and drafted the first manuscript. CP and LF contributed to study design, defined objectives and hypotheses, supported interpretation of results, and provided substantial revisions. CTR and FH contributed to the development of the study protocol and questionnaire. DS supported recruitment organisation, data collection logistics, and data preparation. ML contributed to qualitative analysis. All authors critically reviewed the manuscript and approved the final version. Funding This study was supported by contributions from Pfizer and Kyowa Kirin Pharma. These organisations had no role in the conceptualisation, conduct, analysis or writing of the study. Ethical approval According to French regulations governing non-interventional survey-based research involving healthcare professionals, formal ethical committee approval was not required. The study complied with applicable data protection regulations. All participants received information about the study and provided electronic informed consent prior to participation. Responses were collected anonymously. Competing interests The authors declare that they have no competing interests. References Remec ZI et al. Next-Generation Sequencing in Newborn Screening: A Review of Current State. Front Genet 2021; 12. doi: 10.3389/fgene.2021.662254 . Woerner AC, Gallagher RC, Vockley J, Adhikari AN. The Use of Whole Genome and Exome Sequencing for Newborn Screening: Challenges and Opportunities for Population Health. Front Pediatr 2021; 9: 652. Bick D et al. Newborn Screening by Genomic Sequencing: Opportunities and Challenges. Int J Neonatal Screen 2022; 8: 40. Kingsmore SF. 2022: A pivotal year for diagnosis and treatment of rare genetic diseases. Mol Case Stud 2022;: mcs.a006204. Kingsmore SF et al. A genome sequencing system for universal newborn screening, diagnosis, and precision medicine for severe genetic diseases. Am J Hum Genet 2022; 109: 1605–1619. Ding S, Han L. Newborn screening for genetic disorders: Current status and prospects for the future. Pediatr Investig 2022; 6: 291–298. Holm IA et al. The BabySeq project: implementing genomic sequencing in newborns. BMC Pediatr 2018; 18: 225. Ceyhan-Birsoy O et al. Interpretation of Genomic Sequencing Results in Healthy and Ill Newborns: Results from the BabySeq Project. Am J Hum Genet 2019; 104: 76–93. Ulm E, Feero WG, Dineen R, Charrow J, Wicklund C. Genetics Professionals’ Opinions of Whole-Genome Sequencing in the Newborn Period. J Genet Couns 2015; 24: 452–463. Iskrov G, Ivanov S, Wrenn S, Stefanov R. Whole-Genome Sequencing in Newborn Screening—Attitudes and Opinions of Bulgarian Pediatricians and Geneticists. Front Public Health 2017; 5. https://www.frontiersin.org/article/ 10.3389/fpubh.2017.00308 (accessed 3 Mar2022). Pereira S et al. Perceived Benefits, Risks, and Utility of Newborn Genomic Sequencing in the BabySeq Project. Pediatrics 2019; 143: S6–S13. van Dijk T et al. Expanding Neonatal Bloodspot Screening: A Multi-Stakeholder Perspective. Front Pediatr 2021; 9: 1078. Andrews SM, Porter KA, Bailey DB, Peay HL. Preparing newborn screening for the future: a collaborative stakeholder engagement exploring challenges and opportunities to modernizing the newborn screening system. BMC Pediatr 2022; 22: 90. Wu X, Yang Y, Zhou L, Long W, Yu B. Are We Ready for Newborn Genetic Screening? A Cross-Sectional Survey of Healthcare Professionals in Southeast China. Front Pediatr 2022; 10. https://www.frontiersin.org/articles/ 10.3389/fped.2022.875229 (accessed 15 Oct2022). Cao M, Notini L, Ayres S, Vears DF. Australian healthcare professionals’ perspectives on the ethical and practical issues associated with genomic newborn screening. J Genet Couns 2023; 32: 376–386. White S et al. Expanding the Australian Newborn Blood Spot Screening Program using genomic sequencing: do we want it and are we ready? Eur J Hum Genet 2023; 31: 703–711. Bayrak R, Ünsal A, Güneş A. The knowledge level of the healthcare professionals responsible for newborns’ heel prick tests. J Pediatr Nurs 2024; 78: 133–141. Scarfe J et al. ‘Jumping too far ahead’: Australian healthcare professional, scientist, and policy maker perspectives on using genomics in newborn screening. Eur J Hum Genet EJHG 2025. doi: 10.1038/s41431-025-01954-2 . Haute Autorité de Santé. Dépistage néonatal: critères d’évaluation pour l’intégration de nouvelles maladies au programme national du dépistage à la naissance. 2023 https://www.has-sante.fr/jcms/p_3421858/fr/depistage-neonatal-criteres-d-evaluation-pour-l-integration-de-nouvelles-maladies-au-programme-national-du-depistage-a-la-naissance (accessed 29 Jan2026). Level C et al. Genomic newborn screening in France: from a social acceptability study to a pilot project. In: 56th Annual Conference of the European-Society-of-Human-Genetics (ESHG) . SPRINGERNATURE: Glasgow, United Kingdom, 2023 https://hal.science/hal-04513430 (accessed 29 Jan2026). Peay HL et al. Education and Consent for Population-Based DNA Screening: A Mixed-Methods Evaluation of the Early Check Newborn Screening Pilot Study. Front Genet 2022; 13: 891592. Hayeems RZ, Luca S, Assamad D, Bhatt A, Ungar WJ. Utility of Genetic Testing from the Perspective of Parents/Caregivers: A Scoping Review. Children 2021; 8: 259. Chambers D et al. The acceptability of blood spot screening and genome sequencing in newborn screening: a systematic review examining evidence and frameworks. Health Technol Assess 2025;: 1–53. Genetti CA et al. Parental interest in genomic sequencing of newborns: enrollment experience from the BabySeq Project. Genet Med Off J Am Coll Med Genet 2019; 21: 622–630. Downie L et al. Exome sequencing in newborns with congenital deafness as a model for genomic newborn screening: the Baby Beyond Hearing project. Genet Med 2020; 22: 937–944. Roman TS et al. Genomic Sequencing for Newborn Screening: Results of the NC NEXUS Project. Am J Hum Genet 2020; 107: 596–611. Downie L, Halliday J, Lewis S, Amor DJ. Principles of Genomic Newborn Screening Programs: A Systematic Review. JAMA Netw Open 2021; 4: e2114336. Hao C et al. Newborn screening with targeted sequencing: a multicenter investigation and a pilot clinical study in China. J Genet Genomics Yi Chuan Xue Bao 2022; 49: 13–19. Pichini A et al. Developing a National Newborn Genomes Program: An Approach Driven by Ethics, Engagement and Co-design. Front Genet 2022; 13. https://www.frontiersin.org/articles/10.3389/fgene .2022.866168 (accessed 11 Jan2023). Balciuniene J et al. At-Risk Genomic Findings for Pediatric-Onset Disorders From Genome Sequencing vs Medically Actionable Gene Panel in Proactive Screening of Newborns and Children. JAMA Netw Open 2023; 6: e2326445. Bros-Facer V, Taylor S, Patch C. Next-generation sequencing-based newborn screening initiatives in Europe: an overview. Rare Dis Orphan Drugs J 2023; 2: N/A-N/A. Chen T et al. Genomic Sequencing as a First-Tier Screening Test and Outcomes of Newborn Screening. JAMA Netw Open 2023; 6: e2331162. Garnier N et al. Genetic newborn screening and digital technologies: A project protocol based on a dual approach to shorten the rare diseases diagnostic path in Europe. PloS One 2023; 18: e0293503. Wang X et al. Newborn genetic screening is highly effective for high-risk infants: A single-centre study in China. J Glob Health 2023; 13: 04128. Chung WK, Kanne SM, Hu Z. An Opportunity to Fill a Gap for Newborn Screening of Neurodevelopmental Disorders. Int J Neonatal Screen 2024; 10: 33. Cope H et al. Use of a web-based portal to return normal individual research results in Early Check: Exploring user behaviors and attitudes. Clin Genet 2023; 103: 672–680. Dangouloff T et al. Feasibility and Acceptability of a Newborn Screening Program Using Targeted Next-Generation Sequencing in One Maternity Hospital in Southern Belgium. Children 2024; 11: 926. Lunke S et al. Feasibility, acceptability and clinical outcomes of the BabyScreen+ genomic newborn screening study. Nat Med 2025; 31: 4236–4245. Ziegler A, Chung WK. Universal newborn screening using genome sequencing: early experience from the GUARDIAN study. Pediatr Res 2024;: 1–5. Ziegler A et al. Expanded Newborn Screening Using Genome Sequencing for Early Actionable Conditions. JAMA 2025; 333: 232–240. Boemer F et al. Population-based, first-tier genomic newborn screening in the maternity ward. Nat Med 2025; 31: 1339–1350. Rahman S, Bick D, Scott RH. Whole genome sequencing to screen 100 000 newborns for treatable genetic disorders. J Inherit Metab Dis 2024; 47: 7–8. Goldenberg AJ, Ponsaran R, Gaviglio A, Simancek D, Tarini BA. Genomics and Newborn Screening: Perspectives of Public Health Programs. Int J Neonatal Screen 2022; 8: 11. Gold NB et al. Perspectives of Rare Disease Experts on Newborn Genome Sequencing. JAMA Netw Open 2023; 6: e2312231. Milko LV, Berg JS. Age-Based Genomic Screening during Childhood: Ethical and Practical Considerations in Public Health Genomics Implementation. Int J Neonatal Screen 2023; 9: 36. Downie L et al. Gene selection for genomic newborn screening: moving towards consensus? Genet Med 2024;: 101077. Horton R et al. Challenges of using whole genome sequencing in population newborn screening. BMJ 2024; 384: e077060. Minten T et al. Data-driven consideration of genetic disorders for global genomic newborn screening programs. MedRxiv Prepr Serv Health Sci 2025;: 2024.03.24.24304797. Green RC et al. Actionability of unanticipated monogenic disease risks in newborn genomic screening: Findings from the BabySeq Project. Am J Hum Genet 2023; 110: 1034–1045. Bick D, Bick SL, Dimmock DP, Fowler TA, Caulfield MJ, Scott RH. An online compendium of treatable genetic disorders. Am J Med Genet C Semin Med Genet 2021; 187: 48–54. URL International Consortium on Newborn Sequencing (ICoNS): https://www.iconseq.org/the-consortium Additional Declarations There is no duality of interest Supplementary Files Supplementaltable1.docx Supplemental table 1: Characteristics of the population by modules FigS4.png Supplemental figure 4: Professionals’ views on searching for different types of genetic findings in NBS (N=874) FigS6.png Supplemental figure 6: Anticipated parental reactions and expectations regarding the integration of NGS into NBS (N=751) FigS3.png Supplemental figure 3: Most and least important Wilson–Jungner criteria selected by respondents (N=1,077) FigS1.png Supplemental figure 1: The SeDeN-p2 project within the SeDeN project FigS2.png Supplemental figure 2: Flowchart of the study population and analytical samples FigS5.png Supplemental figure 5: Overall agreement and between-specialty variability for statements related to the integration of NGS into NBS (N=751) SupplementaryMaterials.pdf Supplemental material Cite Share Download PDF Status: Under Review Version 1 posted Review # 3 received at journal 16 Apr, 2026 Reviewer # 3 agreed at journal 24 Mar, 2026 Reviewer # 2 agreed at journal 23 Mar, 2026 Reviewer # 1 agreed at journal 09 Mar, 2026 Reviewers invited by journal 24 Feb, 2026 Submission checks completed at journal 23 Feb, 2026 First submitted to journal 23 Feb, 2026 Unknown event 03 Feb, 2026 Editor assigned by journal 30 Jan, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8743981","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":595629607,"identity":"af38ee0e-682e-4572-86d8-fda05d256e3a","order_by":0,"name":"Camille Level","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABDUlEQVRIie3PMUvDQBTA8SeBy/Jo1idC/QonLg4Sv8o9AnGqFFwyOLRLXURnQfwMlULnJwddzAdwEMzUSSHg4qaXBEUlqbqJ3H9Ijrv8eBcAn++PJsUQoFetigyMe2kh9wxHK4jRAKpamfwDQVkx5p3wpCH1bheJjm/YTdkFFZ5sFXwZH2gJrmQnuwPcaDeUD6aOpKAw39Y8Tw61qKFQvgTsmVaioSYWFKUp8Vx4ev+gZX1iYQ/bL6ajx4q8gNpc7j/zhSOCDcEuQvUUcVOCBfDoB4Ru6ykJKkwsmUXC582/WOwi0dlgVpZZ3I/C63FZHsV8KsHsiTLb7yJvfT4O6OvOt62Vv/ve5/P5/nev6qNgljlP9H0AAAAASUVORK5CYII=","orcid":"","institution":"CHU Dijon Bourgogne","correspondingAuthor":true,"prefix":"","firstName":"Camille","middleName":"","lastName":"Level","suffix":""},{"id":595629608,"identity":"a1f97398-ad4f-4e48-ae73-8871ee83ca47","order_by":1,"name":"Frédéric Huet","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Frédéric","middleName":"","lastName":"Huet","suffix":""},{"id":595629609,"identity":"2c5b8782-9022-46ed-8af9-834ccff73d7c","order_by":2,"name":"Dominique Salvi","email":"","orcid":"","institution":"Université de Bourgogne","correspondingAuthor":false,"prefix":"","firstName":"Dominique","middleName":"","lastName":"Salvi","suffix":""},{"id":595629610,"identity":"f165b57b-de0b-4fa2-a3e1-0098460bfcfc","order_by":3,"name":"Christel Thauvin-Robinet","email":"","orcid":"https://orcid.org/0000-0002-4155-139X","institution":"Hôpital d'Enfants","correspondingAuthor":false,"prefix":"","firstName":"Christel","middleName":"","lastName":"Thauvin-Robinet","suffix":""},{"id":595629615,"identity":"0a6d16aa-4882-4e17-84c8-e118298c682b","order_by":4,"name":"Emmanuel Simon","email":"","orcid":"","institution":"CHU Dijon Bourgogne","correspondingAuthor":false,"prefix":"","firstName":"Emmanuel","middleName":"","lastName":"Simon","suffix":""},{"id":595629616,"identity":"ee358c4a-c261-4087-be51-93e7bb668214","order_by":5,"name":"Margot Lemaitre","email":"","orcid":"","institution":"Université Bourgogne Europe, CHU Dijon Bourgogne, FHU-TRANSLAD, Centre de recherche Translationnelle en Médecine moléculaire – Inserm UMR1231 équipe GAD","correspondingAuthor":false,"prefix":"","firstName":"Margot","middleName":"","lastName":"Lemaitre","suffix":""},{"id":595629620,"identity":"ce954b79-45bf-4e21-8a69-ab20fbb47b58","order_by":6,"name":"Christine Peyron","email":"","orcid":"https://orcid.org/0000-0003-3823-0859","institution":"Université Bourgogne Franche Comté","correspondingAuthor":false,"prefix":"","firstName":"Christine","middleName":"","lastName":"Peyron","suffix":""},{"id":595629622,"identity":"9eabf273-37cd-4760-8eb2-618228f90d54","order_by":7,"name":"Laurence Faivre","email":"","orcid":"https://orcid.org/0000-0001-9770-444X","institution":"Hôpital d'Enfants, CHU et Université de Bourgogne","correspondingAuthor":false,"prefix":"","firstName":"Laurence","middleName":"","lastName":"Faivre","suffix":""}],"badges":[],"createdAt":"2026-01-30 18:05:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8743981/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8743981/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":103590722,"identity":"6514b091-8844-4615-8f37-9947cbc4003e","added_by":"auto","created_at":"2026-02-27 12:07:05","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":636293,"visible":true,"origin":"","legend":"\u003cp\u003ePerinatal healthcare professionals’ views on Wilson and Jungner’s and Andermann’s criteria (N=1,077)\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eStacked bars show the distribution of responses for each criterion (“not at all important”, “moderately important”, “very important”, “no opinion”). Values displayed within bars indicate the number of respondents and the corresponding percentage within each criterion. Criteria are grouped by framework (Wilson–Jungner vs Andermann).\u003c/em\u003e\u003c/p\u003e","description":"","filename":"Fig1.png","url":"https://assets-eu.researchsquare.com/files/rs-8743981/v1/ccf9b1df40fa89d7bd18c111.png"},{"id":103590724,"identity":"51963265-7060-4616-a6a9-fac176684217","added_by":"auto","created_at":"2026-02-27 12:07:05","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":329815,"visible":true,"origin":"","legend":"\u003cp\u003eProfessionals’ views on the genetic findings to be included in an expanded NBS program, stratified by specialty (N=874)\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eThis figure displays, for each category of genetic findings, the overall proportion of respondents rating its inclusion or reporting in NBS as “strongly agree” (x-axis), together with the variability of responses across professional specialties (y-axis, expressed as the standard deviation of specialty-specific proportions). Coloured points represent specialty-specific proportions, while open circles indicate the overall average across specialties. Horizontal lines illustrate the range (minimum–maximum) of specialty-specific values. Categories located toward the right of the figure correspond to higher overall support, whereas higher positions on the y-axis reflect greater heterogeneity of views across specialties.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"Fig2.png","url":"https://assets-eu.researchsquare.com/files/rs-8743981/v1/8e4e8ac63ccba528b80769bb.png"},{"id":103590730,"identity":"c7700374-49a1-4c61-83af-b2c93ab56815","added_by":"auto","created_at":"2026-02-27 12:07:05","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":634006,"visible":true,"origin":"","legend":"\u003cp\u003eResults on the NGS module (N=751); 3A: Overall opinion on using NGS as first-line test in NBS, by specialty; 3B: Opinions on integrating NGS in NBS (all specialties)\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e(A) Distribution of responses by professional specialty to the question of NGS should be used as a first-line test in NBS. Stacked bars represent the proportion of respondents favouring exome or genome sequencing, a limited gene panel, no use of NGS, or reporting no opinion or lack of expertise. Counts and percentages are displayed within segments. Results are shown for each specialty and for all specialties combined. (B) Respondents’ levels of agreement with statements addressing technical performance, result interpretation, organisational feasibility, family impact, and broader ethical considerations related to the integration of NGS into NBS. Stacked bars display the distribution of responses (“strongly agree”, “somewhat agree”, “somewhat disagree”, “strongly disagree”, and “not my field of expertise”) for each statement, with counts and within-item percentages shown. Statements are grouped by thematic category.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"Fig3.png","url":"https://assets-eu.researchsquare.com/files/rs-8743981/v1/3daf3175fcf8b27ab3d28c79.png"},{"id":104399168,"identity":"d9757da0-df1a-4f3e-9562-8b4dde240558","added_by":"auto","created_at":"2026-03-11 12:04:57","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":544679,"visible":true,"origin":"","legend":"\u003cp\u003ePerceptions of information, consent, and professional training related to NBS and NGS (N=751)\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e(A) Professionals’ perceptions of the level of information currently provided to families within the NBS program. (B) Professionals’ perceptions of how the non-mandatory nature of NBS is conveyed to families. (C) Self-assessed level of training for understanding NGS results. (D) Self-assessed level of training for discussing NGS results with patients and families. Stacked bars represent the percentage of responses by professional specialty and for all specialties combined; counts and percentages are displayed within segments. acceptability of gNBS, including their methodological characteristics, study populations, and key findings.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"Fig4.png","url":"https://assets-eu.researchsquare.com/files/rs-8743981/v1/cf4ad7c4e71c3d1cad6a8b1c.png"},{"id":104410397,"identity":"7916488b-d312-4db5-8c35-850d04253c33","added_by":"auto","created_at":"2026-03-11 12:51:59","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2879336,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8743981/v1/61608028-1ef2-46d9-aa73-45eda04ada64.pdf"},{"id":104399456,"identity":"c0db17c9-ec73-4afd-a921-5c015bb34ee4","added_by":"auto","created_at":"2026-03-11 12:06:12","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":41851,"visible":true,"origin":"","legend":"Supplemental table 1: Characteristics of the population by modules","description":"","filename":"Supplementaltable1.docx","url":"https://assets-eu.researchsquare.com/files/rs-8743981/v1/016eb1ece2b2d1ef33e829cb.docx"},{"id":103590723,"identity":"bf1b0973-a8ae-4de4-93eb-55ca87b72194","added_by":"auto","created_at":"2026-02-27 12:07:05","extension":"png","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":300311,"visible":true,"origin":"","legend":"Supplemental figure 4: Professionals\u0026#x2019; views on searching for different types of genetic findings in NBS (N=874)","description":"","filename":"FigS4.png","url":"https://assets-eu.researchsquare.com/files/rs-8743981/v1/a6e849979360bcd3cd831c6c.png"},{"id":103590734,"identity":"74e52990-6a57-46bd-ae68-5e92b490c38c","added_by":"auto","created_at":"2026-02-27 12:07:05","extension":"png","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":356792,"visible":true,"origin":"","legend":"Supplemental figure 6: Anticipated parental reactions and expectations regarding the integration of NGS into NBS (N=751)","description":"","filename":"FigS6.png","url":"https://assets-eu.researchsquare.com/files/rs-8743981/v1/45e03f8a622e733f2eb25e8a.png"},{"id":103590732,"identity":"29860d7b-b0b2-42d8-a0ac-0f3313d5d5cd","added_by":"auto","created_at":"2026-02-27 12:07:05","extension":"png","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":167971,"visible":true,"origin":"","legend":"Supplemental figure 3: Most and least important Wilson\u0026#x2013;Jungner criteria selected by respondents (N=1,077)","description":"","filename":"FigS3.png","url":"https://assets-eu.researchsquare.com/files/rs-8743981/v1/b38d245e4e0e42720eb8ac76.png"},{"id":103590727,"identity":"502c6cf9-eb8d-4462-b8bd-df9493d36635","added_by":"auto","created_at":"2026-02-27 12:07:05","extension":"png","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":532687,"visible":true,"origin":"","legend":"Supplemental figure 1: The SeDeN-p2 project within the SeDeN project","description":"","filename":"FigS1.png","url":"https://assets-eu.researchsquare.com/files/rs-8743981/v1/1522b302a16d1dacbf2f57fd.png"},{"id":103590726,"identity":"abf1a148-d033-4235-ac13-da03d7f44205","added_by":"auto","created_at":"2026-02-27 12:07:05","extension":"png","order_by":6,"title":"","display":"","copyAsset":false,"role":"supplement","size":68249,"visible":true,"origin":"","legend":"Supplemental figure 2: Flowchart of the study population and analytical samples","description":"","filename":"FigS2.png","url":"https://assets-eu.researchsquare.com/files/rs-8743981/v1/6443133ced7986d114601395.png"},{"id":103590729,"identity":"cd08dfb5-8eb4-472d-9397-bb18295d78b7","added_by":"auto","created_at":"2026-02-27 12:07:05","extension":"png","order_by":7,"title":"","display":"","copyAsset":false,"role":"supplement","size":389660,"visible":true,"origin":"","legend":"Supplemental figure 5: Overall agreement and between-specialty variability for statements related to the integration of NGS into NBS (N=751)","description":"","filename":"FigS5.png","url":"https://assets-eu.researchsquare.com/files/rs-8743981/v1/e9505ffc13164be5a626395f.png"},{"id":104399157,"identity":"817a44c5-d0b1-4fae-bac5-a8ccccaaf051","added_by":"auto","created_at":"2026-03-11 12:04:54","extension":"pdf","order_by":8,"title":"","display":"","copyAsset":false,"role":"supplement","size":1208771,"visible":true,"origin":"","legend":"Supplemental material","description":"","filename":"SupplementaryMaterials.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8743981/v1/dacc65d8e1d2c2514df02cd3.pdf"}],"financialInterests":"There is no duality of interest","formattedTitle":"Healthcare Professionals’ Views on Expanding Newborn Screening with or without Genomics in France: Results of the SeDeN-p2 Study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eNewborn screening (NBS) is a major public health programme enabling early detection and treatment of severe congenital disorders. Traditionally based on biochemical assays targeting a limited number of conditions, it has evolved alongside scientific and technological advances. The development of next-generation sequencing (NGS), declining genomic costs, and increasing therapeutic options for rare diseases have renewed interest in expanding screening \u003csup\u003e\u003cspan additionalcitationids=\"CR2 CR3 CR4 CR5\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThese developments have raised international debates on the responsible integration of genomic approaches into public health and on which conditions should be included. In the late 2010s, initiatives such as the BabySeq Project in the United States helped structure these discussions. At that time, French NBS remained limited to severe childhood-onset conditions, mainly identified through biochemical testing, with genetics used as a second-tier tool. Meanwhile, no structured national assessment of healthcare professionals\u0026rsquo; views on genomic NBS (gNBS) was available. Recent revisions of French bioethics laws have since created a more favourable framework for innovation \u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e,\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. In this context, the F\u0026eacute;d\u0026eacute;ration Hospitalo-Universitaire TRANSLAD launched the SeDeN project (\u003cem\u003eS\u0026eacute;quen\u0026ccedil;age et D\u0026eacute;pistage N\u0026eacute;onatal\u003c/em\u003e) to examine expectations and barriers related to NBS expansion, including genomic approaches. The project comprises several components: policy analysis (SeDeN-p1), healthcare professionals (SeDeN-p2), parents (SeDeN-p3), and policymakers and stakeholders (SeDeN-p4) (Supplemental Figure \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThis article reports findings from SeDeN-p2. The study assessed how healthcare professionals involved in perinatal care and genetics in France perceive potential NBS expansion, with and without first-line genetic testing. It aimed to measure levels of acceptability across types of conditions and to identify areas of consensus, divergence, and perceived ethical, organisational, and informational constraints.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThe SeDeN-p2 study employed a nationwide survey-based methodology designed to capture a wide range of opinions from HCPs in France on the topic of expanding NBS, including genetic technologies. SeDeN-p2 consisted of an exploratory qualitative phase aimed at assisting in the design of a questionnaire aligned with field-related concerns, followed by a quantitative investigative phase based on a self-administered survey.\u003c/p\u003e \u003cp\u003e The preliminary interviews were conducted in accordance with the COREQ guidelines. A purposive sample was selected to ensure variation in professional background, practice setting, and involvement in perinatal care. Fifteen participants were interviewed, including obstetricians, paediatricians, midwives, biologists, clinical geneticists, and public policymakers. Semi-structured interviews were conducted online by CL between November 2020 and April 2021, audio-recorded, transcribed, and anonymised. Interviews lasted on average 1 hour and 33 minutes and were analysed using thematic analysis supported by NVivo software (version 12 Pro).\u003c/p\u003e \u003cp\u003eThis exploratory qualitative phase was used to refine the content of a nationwide online questionnaire. It led to the identification of four key domains: (i) criteria for selecting conditions for NBS; (ii) scope of conditions and types of results to be reported; (iii) attitudes toward the integration of NGS into NBS; and (iv) expectations and practices regarding parental information and consent. These findings informed the questionnaire design to ensure alignment with the diversity and coherence of professional perspectives.\u003c/p\u003e \u003cp\u003eAccordingly, the questionnaire was constructed as a four-module questionnaire, each module corresponding to one of these domains and addressing: (i) criteria guiding condition selection, (ii) scope of genetic findings, (iii) views on NGS integration, and (iv) information practices. Because completion rates differed across modules, the number of responses included in the analyses varied by module. A module-based analytical strategy was therefore defined \u003cem\u003ea priori\u003c/em\u003e: analyses were conducted separately within each thematic block, prioritising interpretative coherence over maximising a single overall sample size. Detailed descriptions of the questionnaire content, response scales, and analytical procedures, including inclusion thresholds and comparability checks, are provided in the Supplemental Methods S1 and Supplemental Figure S2.\u003c/p\u003e \u003cp\u003eThe survey was administered online between June and December 2021. It was disseminated nationwide through professional networks and learned societies representing paediatricians, medical geneticists, genetic counsellors, gynaecologists, and midwives. Dissemination relied on professional mailing lists and, for several learned societies, publication of the survey link on their official websites. Participation was voluntary and not accompanied by any financial reward. All participants were invited to provide informed consent for the processing of data in accordance with the research protocol.\u003c/p\u003e \u003cp\u003eAnalyses were primarily descriptive and comparative across questionnaire modules. Categorical variables were summarised as counts and percentages within each module-specific analytical subsample. Missing data were reported explicitly and were not imputed. Comparisons across subgroups, including professional specialties were mainly based on observed differences in proportions and interpreted descriptively. Qualitative open text responses were used illustratively to enrich the interpretation of quantitative results. Items assessing opinions on categories of genetic findings or NGS-related statements were displayed in two-dimensional \u0026ldquo;landscape\u0026rdquo; plots using R via Rstudio (version 4.4.2.), showing for each item (i) overall agreement, (ii) variability across specialties and (iii) the min\u0026ndash;max range of specialty-specific responses. In addition, for a limited number of key outcomes, namely the prioritisation of screening criteria and the overall position on NGS integration, exploratory global tests of association with professional specialty were conducted. Given small expected cell counts in several contingency tables, Fisher\u0026rsquo;s exact test was used when appropriate.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eSociodemographic and professional characteristics\u003c/h2\u003e \u003cp\u003eAcross all modules, respondents covered a wide range of medical specialties and practice settings. Paediatricians represented the largest professional group, accounting for approximately 43\u0026ndash;44% of respondents across modules, while midwives constituted the second largest group, representing around 20\u0026ndash;24%. These were followed by medical geneticists, gynaecologists and genetic counsellors. Approximately half of the respondents worked in university hospitals, and around one third reported complementary academic activities, including teaching or research. Most participants were mid-career (43\u0026ndash;44%) or senior (34%) professionals, and the majority reported regular involvement in NBS activities. Engagement with genetics-related practices was common: more than half reported direct experience with patients affected by rare diseases, and over three quarters reported experience with genetic testing. The sample was predominantly female, with respondents distributed across age groups and family situations. A detailed description of sociodemographic and professional characteristics for each module-specific analytical sample is provided in Supplemental Table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eCriteria for NBS module\u003c/h3\u003e\n\u003cp\u003eIn this section (N\u0026thinsp;=\u0026thinsp;1,077), all the proposed criteria for assessing NBS were rated as important, although differences emerged in the level of importance attributed to each (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Criteria directly related to expected clinical benefits, including the superiority of early treatment outcomes, the test ability to detect the condition at an early stage, test performance, and test acceptability, received near-unanimous support (83\u0026ndash;87% \u0026ldquo;Very important\u0026rdquo;). In contrast, criteria related to economic considerations or organisational flexibility, such as cost-effectiveness or the possibility of repeating the test, were more frequently rated as of secondary importance (resp. 35% and 23% \u0026ldquo;Very important\u0026rdquo;). Among the Andermann criteria, equity and access to screening for the entire target population was the most strongly supported (94% \u0026ldquo;Very important\u0026rdquo;). Across Wilson and Jungner, and Andermann frameworks, respondents consistently agreed that the expected benefits should outweigh the potential harms (84\u0026ndash;89% \u0026ldquo;Very important\u0026rdquo;). When asked to prioritize, respondents selected the superiority of early treatment outcomes as the single most important criterion for 59%, compared with disease severity (12%) or early detection (8%) (Supplemental Figure S3). Conversely, the possibility of repeating the test and cost considerations were most frequently identified as the least important criteria (resp. 30% and 36%), further illustrating the predominance of clinical benefit over economic or organisational aspects in respondents\u0026rsquo; judgments.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003ePrioritisation patterns differed according to professional specialty, experience with genetics, practice setting, and sociodemographic characteristics. Overall, specialty and genetic expertise showed the most consistent associations with governance-, evaluation-, and safeguard-related criteria, whereas frontline and non-university settings were more frequently associated with criteria emphasising population relevance and implementation feasibility. Detailed cross-tabulations and statistical associations are provided in the Supplemental Analysis S1.\u003c/p\u003e \u003cp\u003eWhen invited to suggest additional criteria they considered important for deciding whether a condition should be included in NBS, a small proportion of respondents (n\u0026thinsp;=\u0026thinsp;67; 6.7%) provided open-ended comments. Most of these responses did not introduce entirely new criteria, but rather reiterated or specified dimensions already captured by existing frameworks. Respondents most frequently emphasised the availability of effective treatment and the potential for early intervention to modify morbidity or mortality, often stressing that direct benefit to the child should prevail over considerations of prevalence or cost. Other comments referred to disease severity, expected quality-of-life gains, and the balance between psychological and clinical burden. Ethical considerations were also raised, including consent shortly after birth, parental decision-making on behalf of the child, and the need for adequate information and psychological support.\u003c/p\u003e\n\u003ch3\u003eGenetic findings module\u003c/h3\u003e\n\u003cp\u003eIn the genetic findings module (N\u0026thinsp;=\u0026thinsp;874), 44% of respondents considered the current scope of NBS in France insufficient, 29% judged it adequate, and 27% expressed no opinion. Strong agreement was reported for childhood-onset conditions with curative potential (76% strongly agree; 19% somewhat agree) and for conditions in which early intervention could improve prognosis (83% strongly agree; 15% somewhat agree). Agreement remained high, though less unanimous when the benefit applied only in adulthood, however 72\u0026ndash;82% strongly agree/somewhat agree, and when genetic findings offered only indirect or delayed benefits, such as pharmacogenetic information (66% strongly agree/somewhat agree). By contrast, findings without direct medical benefit for the child received limited support, including information primarily relevant for relatives (31% strongly agree/somewhat agree), carrier status (30% strongly agree/somewhat agree), and variants of uncertain significance (12% strongly agree/somewhat agree) (Supplemental Figure S4).\u003c/p\u003e \u003cp\u003eResponse patterns varied across professional profiles (differences by specialty are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e; additional cross-analyses are reported in the Supplemental Analysis S1). Medical geneticists and genetic counsellors consistently appeared as the least favourable profiles overall, except for childhood-onset conditions with clear clinical actionability (all p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). In contrast, midwives and gynaecologists were among the most favourable groups across a broad range of genetic findings, contributing to higher overall agreement rates, particularly for childhood actionable categories (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05), adult-onset actionable variants (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05), and information relevant for relatives (p\u0026thinsp;\u0026lt;\u0026thinsp;0.01). Paediatricians occupied an intermediate position, generally slightly less supportive than the overall mean, with significant associations observed for childhood non-actionable findings (p\u0026thinsp;\u0026lt;\u0026thinsp;0.01) and adult-onset variants (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05), but less systematic differences across other categories. Greater exposure to genetics and academic involvement were associated with more cautious positions, especially for adult-onset non-actionable variants, carrier status, and variants of uncertain significance, whereas professionals in private or mixed practice tended to express broader support. Younger respondents were generally more favourable to wider disclosure, while more senior professionals adopted more restrictive positions.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e\n\u003ch3\u003eNGS Module\u003c/h3\u003e\n\u003cp\u003eRegarding possible modalities for integrating NGS into NBS (N\u0026thinsp;=\u0026thinsp;751), only one third of respondents reported being unable to take a position, mainly because they did not consider the issue within their field of expertise; a small additional fraction expressed no opinion. Overall, 52.2% supported a limited panel, 2.9% endorsed exome or genome sequencing, and 10.4% favoured avoiding NGS altogether. Positions differed significantly across specialties (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), highlighting marked heterogeneity (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eA). For technical items (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eB), such as whether NGS produces too many false positives or negatives, whether it would be more efficient than current techniques, or whether sufficient evidence of technical performance or benefit\u0026ndash;risk balance exists, \u0026ldquo;Not my field of expertise\u0026rdquo; was frequently selected (44\u0026ndash;50%). Among those expressing an opinion, no clear majority emerged. Organisational items elicited more definite positions, although statements regarding operational feasibility, long-term cost\u0026ndash;benefit balance, or turnaround times still showed high levels of self-reported lack of expertise (44\u0026ndash;51%). By contrast, items related to professional roles and system organisation generated clearer agreement: 58.4% supported mandatory genetics consultation (25.6% strongly, 32.8% somewhat), and 57.7% agreed that health professionals are insufficiently trained in genetics (20.6% strongly, 37.1% somewhat). Ethical and societal items were less polarised but largely supported. About 70% agreed that NGS would raise ethical issues (20.2% strongly, 49.6% somewhat). Concerns about data misuse (62.2%), future child autonomy (57.6%), family anxiety (62.9%), and anxiety related to adult-onset risk (65.6%) were also frequently endorsed.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eAgreement patterns differed sharply across specialties across all domains (Supplemental Figure S5). Technical and organisational items showed particularly strong structuring effects: operational feasibility, turnaround times, insufficient training, and difficulties limiting returned information were strongly associated with specialty and genetic exposure (all p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Geneticists and genetic counsellors expressed the highest levels of concern, whereas midwives and, to a lesser extent, gynaecologists were less likely to endorse these limitations. For technical performance, genetic specialists were more favourable overall but more explicit about current limitations. Items related to family experience and psychosocial impact showed a distinct pattern. Higher levels of agreement with statements emphasising anxiety for families or potential psychosocial burden were observed among paediatricians and genetic counsellors, with significant associations according to specialty, parenthood, and age (all p\u0026thinsp;\u0026lt;\u0026thinsp;0.01). Medical geneticists, by contrast, expressed lower levels of agreement with these items, indicating a relative distancing from psychosocial considerations compared with perinatal and counselling-oriented profiles. Broader ethical and societal concerns including data misuse, ethical complexity, and child autonomy, were strongly associated with specialty, genetic expertise, and practice setting (most p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Genetic counsellors, and for several items paediatricians, more frequently endorsed these concerns, whereas midwives and gynaecologists were less likely to prioritise them. These patterns indicate stronger alignment of genomics-oriented and child-centred profiles with ethical boundary-setting, particularly when long-term or societal implications are foregrounded.\u003c/p\u003e \u003cp\u003eWhen asked how parents might react to the integration of NGS into NBS (Supplemental Figure S6), respondents most often anticipated questioning attitudes (53%), followed by anxiety (29%) and confidence (19%). Differences by specialties were less pronounced, although medical geneticists more often anticipated confidence, paediatricians more often anxiety, and genetic counsellors questioning attitudes. Regarding parental expectations, 59% anticipated divided parental positions, 30% active demand, 8% reluctance, and 4% indifference.\u003c/p\u003e \u003cp\u003eQualitative comments (71 on organisational impact, 66 on technical issues, 82 on family impact) reiterated the necessity of comprehensive planning before implementation. Many emphasized that current infrastructures, particularly in non-specialized settings, would be strained by widespread adoption of NGS in NBS. Participants voiced concerns over result interpretation, risk of incidental findings, and the burden of VUS. Ethical apprehensions centred on informed consent, the preservation of child autonomy, and the appropriate return of uncertain results.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eFamily Information module\u003c/h2\u003e \u003cp\u003eRespondents (N\u0026thinsp;=\u0026thinsp;751) were also asked about the timing, content, and format of parental information on NBS. Most considered current information insufficient: over two thirds rated it as \u0026ldquo;moderate\u0026rdquo; (37%) or \u0026ldquo;low\u0026rdquo; (32%) (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eA), and 62% believed parents are rarely aware that NBS is not mandatory (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eB). Differences by specialty were marked: geneticists and genetic counsellors were the most critical, whereas midwives reported more favourable assessments for both questions.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe survey also revealed a broad perception of insufficient professional training in relation to NGS among respondents included in the NGS module. When asked \u0026ldquo;\u003cem\u003eWith your current knowledge, how prepared do you feel to understand potential results from next-generation sequencing?\u003c/em\u003e\u0026rdquo; (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eC), fewer than 13% of respondents considered themselves \u0026lsquo;perfectly\u0026rsquo; trained, mainly medical geneticists and genetic counsellors. When invited to consider a second question - \u0026lsquo;\u003cem\u003eIf NGS were integrated into newborn screening, how prepared would you feel to discuss these results and answer parents\u0026rsquo; questions?\u003c/em\u003e\u0026rsquo; (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eD) - fewer than 7% reported feeling fully able to do so. Across both items, 60\u0026ndash;70% rated themselves poorly or very poorly trained, with a marked drop between technical understanding and communicative readiness. Differences by specialty were substantial: medical geneticists reported the highest confidence, while perinatal professionals, especially midwives, reported the lowest, with over 90% considering their training insufficient. Additional analyses by practice setting and sociodemographic characteristics are presented in the Supplemental Analysis S1.\u003c/p\u003e \u003cp\u003eRegarding timing, respondents favoured late pregnancy (third trimester, 68%) and the first three postnatal days (79%), whereas preconception (10%) and first trimester (12%) were rarely endorsed. Direct discussion with a health professional was overwhelmingly preferred (94%), followed by written materials (77%), while digital tools and group sessions were less frequently selected (both 32%). In terms of content, respondents prioritised information on screened diseases (78%), treatment or management options (60%), and health impact (53%). False positives and negatives were also considered important (48%), whereas sample storage (6%) and research use (5%) were seldom prioritised (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eProfessionals\u0026rsquo; views on the timing, modalities, and content of parental information regarding NBS (N\u0026thinsp;=\u0026thinsp;751) \u003cem\u003eThis table summarizes professionals\u0026rsquo; views on the preferred timing, modalities, and content of information provided to parents about NBS, including when information should be delivered, how it should be communicated, and which topics should be prioritized. Results are reported as absolute numbers, with percentages shown in parentheses. Because these items were assessed using multiple-choice questions, respondents could select more than one option. As a result, percentages may sum to more than 100%. Percentages are calculated based on the total number of respondents (N\u0026thinsp;=\u0026thinsp;751).\u003c/em\u003e\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003en (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThe moment(s) you consider the most appropriate to explain NBS to families\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1. Before pregnancy (birth planning, desire for children, etc.) / Preconceptional period\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e76 (10%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2. At the beginning of pregnancy (1st trimester)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e89 (12%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3. In the middle of pregnancy (2nd trimester)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e194 (26%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4. At the end of pregnancy (3rd trimester)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e507 (68%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5. Upon arrival at the maternity ward / At childbirth\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e56 (7.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6. Within 3 days after childbirth / Postnatal (within 3 days)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e594 (79%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eThe way(s) you consider effective to inform parents about NBS before testing\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1. Discussion with a healthcare professional\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e705 (94%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2. A leaflet or brochure / Educational booklet\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e582 (77%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3. A website / Digital modalities (internet, mobile app, etc.)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e238 (32%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4. An information meeting (e.g., at the maternity ward) / Group information\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e244 (32%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5. Other\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (0.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eThe information you consider essential to be given\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1. The names of the diseases included in the screening\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e584 (78%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2. The possible effects of the detected diseases on my baby\u0026rsquo;s health / The impact of each condition on the child\u0026rsquo;s health\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e398 (53%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3. The number of babies born with these diseases each year / The prevalence of conditions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e222 (30%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4. The possibilities for treatment/management if my baby is sick / What can be done to manage the child if diagnosed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e451 (60%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5. The risk of false positives and false negatives\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e361 (48%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6. Storage of dried blood spots (duration, possible reanalysis, etc.)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e47 (6.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e7. If dried blood spots are used for research\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e38 (5.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e8. Other\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19 (2.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe SeDeN-p2 study provides a large-scale national assessment of HCPs\u0026rsquo; perspectives on the expansion of NBS in France, including genomic integration. By surveying the largest and most diverse sample of perinatal professionals studied to date across an entire country, including overseas territories, it addresses a gap identified in previous literature, which was generally limited in size, scope, or specialty representation (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e)\u003csup\u003e\u003cspan additionalcitationids=\"CR10 CR11 CR12 CR13 CR14 CR15 CR16 CR17\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e. It is the only study to include gynaecologists and midwives at this scale, although they are central to NBS delivery in maternity settings. Its quantitative design, informed by prior qualitative work and complemented by open-ended responses, also allows comparison across professional groups.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSummary of Selected International Studies on Professional Acceptability of gNBS \u003cem\u003eThis table presents a non-exhaustive overview of selected international studies examining healthcare professionals\u0026rsquo; acceptability of gNBS, including their methodological characteristics, study populations, and key findings.\u003c/em\u003e\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003cp\u003eCountry\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMethodology\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePopulation\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eKey Findings\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUlm et al., 2015\u003c/p\u003e \u003cp\u003eUSA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eExploratory cross-sectional electronic survey of ACMG members\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e113 genetic professionals\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMost respondents considered that whole-genome sequencing should not currently be used in NBS and should not be mandatory if implemented. Nevertheless, many anticipated GS as a future application. Support was conditional on accurate interpretation, extended consent processes, comprehensive genetic counselling, and comparable costs and turnaround times to existing NBS. Participants endorsed current criteria for inclusion of conditions and expressed reservations about integrating GS into traditional NBS without revisiting these criteria.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIskrov et al., 2017\u003c/p\u003e \u003cp\u003eBulgaria\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eQuantitative study based on a questionnaire\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e120 paediatricians and geneticists\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePaediatricians were more supportive of population-based GS than geneticists, who expressed stronger reservations. Both groups highlighted ethical concerns, the need for strict data protection, and the importance of genetic counselling and psychological support. While non-selective GS was largely considered infeasible, selective GS was viewed as a potentially valuable complement to existing NBS programs.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePereira et al., 2019\u003c/p\u003e \u003cp\u003eUSA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eQuantitative survey combining closed-ended questions and open-ended responses\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e144 paediatricians (and 493 parents of infants enrolled in the BabySeq project)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eBoth parents and clinicians perceived greater risks associated with GS than with conventional NBS. Parents nevertheless anticipated more benefits and fewer risks than clinicians. Clinicians expressed stronger concerns regarding privacy and discrimination, whereas parents emphasized potential benefits extending beyond immediate clinical utility.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003evan Dijk et al., 2021\u003c/p\u003e \u003cp\u003eNetherlands\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eQualitative study based on semi-structured interviews\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22 professionals HCPs, test developers, policy makers (and 17 parents of children with normal or abnormal NBS results)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eParticipants generally supported expanding NBS when restricted to treatable conditions. Concerns focused on uncertain findings, untreatable disorders, and the complexity of informed consent. Two contrasting perspectives emerged: a targeted-scope approach prioritising neonatal health benefits with limited parental choice, and a broader-scope approach emphasising wider benefits, reproductive planning, and parental autonomy. Policymakers were seen as needing to balance these perspectives in future NBS decisions.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAndrews et al., 2022\u003c/p\u003e \u003cp\u003eUSA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMixed-methods stakeholder engagement study combining a pre-panel survey and rapid qualitative analysis of multi-stakeholder panel discussions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e42 expert stakeholders from the United States and Canada representing multiple NBS stakeholder groups\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eStakeholders identified major structural and organisational barriers to NBS modernization, notably insufficient data for decision-making, laboratory capacity constraints, and lengthy state-level implementation timelines. Discussions emphasised infant well-being as the core objective of NBS, while highlighting tensions between the accelerating pipeline of transformative therapies and the limited capacity of existing systems. Modernization was framed as a collective governance challenge requiring evidence-based decisions, increased funding, enhanced coordination, and novel oversight models rather than technological change alone.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWu et al., 2022\u003c/p\u003e \u003cp\u003eChina\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eQuantitative questionnaire-based study\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e258 healthcare professionals from 43 Chinese NBS centres (18% clinicians; 82% laboratory, blood collection, or management staff)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMost respondents expressed interest in gNBS (\u0026asymp;\u0026thinsp;81%) and considered it necessary in the Chinese context (\u0026asymp;\u0026thinsp;98%). Participants largely believed gNBS could expand the range of screened conditions (\u0026asymp;\u0026thinsp;90%), while substantial concerns were raised about the limited availability of genetic counselling (\u0026asymp;\u0026thinsp;73%) and ethical implications. More than half (\u0026asymp;\u0026thinsp;55%) supported a combined approach integrating gNBS with tandem mass spectrometry.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCao et al., 2023\u003c/p\u003e \u003cp\u003eAutralia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eQualitative study based on semi-structured interviews\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 healthcare professionals with clinical or policy experience in NBS and/or next-generation sequencing\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eParticipants generally considered GS not yet appropriate for routine NBS, although most anticipated its introduction within the next decade. Views diverged regarding eligible conditions and data governance. The need for further research and the central role of genetic counsellors in education, consent, and result disclosure was consistently emphasised.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWhite et al., 2023\u003c/p\u003e \u003cp\u003eAustralia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOnline cross-sectional survey\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e145 healthcare professionals (and 163 parents)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMost healthcare professionals (62%) considered GS premature for current NBS, despite anticipating its use in the near future. Both groups highlighted critical prerequisites, including reliable data interpretation, pre- and post-test counselling, and robust information, consent, and opt-out processes. Overall support was cautious and conditional, emphasising ethical, social, legal, and organisational readiness.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBayrak et al., 2024\u003c/p\u003e \u003cp\u003eTurkey\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCross-sectional descriptive questionnaire study with quantitative analysis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e147 healthcare professionals involved in heel prick screening\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRespondents demonstrated strong knowledge of technical aspects of sample collection, storage, and transport, but notable gaps regarding congenital metabolic diseases, their clinical manifestations, and referral pathways. Knowledge levels varied significantly across occupational groups. Although the study did not address genomic screening directly, it highlights how uneven frontline knowledge may constitute a structural constraint for the effective implementation or extension of NBS programs.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eScarfe et al., 2025\u003c/p\u003e \u003cp\u003eAustralia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eQualitative study using semi-structured interviews and small group discussions with inductive content analysis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19 healthcare professionals and scientists involved in NBS, and 16 policy-makers responsible for program delivery and governance\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eParticipants acknowledged the potential of genomics to improve early detection and diagnosis, but more frequently stressed technical, organisational, and system-level risks. Divergent views emerged on whether gNBS should remain aligned with the current paradigm focused on severe, treatable, early-onset conditions, or justify a broader paradigm shift extending benefits beyond the neonatal period. Effective implementation was considered conditional on system readiness, including national coordination, appropriate consent models, agreed approaches to uncertain results, workforce capacity, infrastructure, and clear ethical and legal frameworks.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eHCP: Healthcare professionals\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eA strong consensus emerged around the clinical foundations of NBS expansion. Actionable childhood diseases with clear clinical pathways and demonstrable benefit from early intervention were overwhelmingly supported, and principles such as equity of access and benefit\u0026ndash;harm balance remained central. Economic and organisational considerations were consistently secondary. These patterns confirm the enduring structuring role of the Wilson \u0026amp; Jungner and Andermann frameworks, reflected in the 2023 HAS criteria\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eGenomic technologies, however, introduce a qualitative shift. By enabling multiple diseases to be screened through a single test, NGS may loosen historical technical constraints and therefore challenge how these criteria are operationalised. The debate no longer concerns only which conditions meet established principles, but also how broadly those principles should be interpreted in a genomic context. In our results, this shift translated into a graded hierarchy of acceptability: strong support for actionable childhood conditions; more conditional support for adult-onset or indirectly beneficial findings; and reluctance toward non-actionable or uncertain variants. Concerns about child autonomy, VUS, and long-term implications underscore the difficulty of defining acceptable limits in a genomic context.\u003c/p\u003e \u003cp\u003eWithin this reconfigured landscape, two professional orientations became visible. One, more frequently associated with perinatal and frontline clinical practice, emphasised feasibility and immediate clinical utility, while also supporting broader disclosure when findings contribute to care pathways, intervention, or family-related benefit. The other, more closely linked to genetic and academic expertise, placed stronger emphasis on analytic validity, governance safeguards, and interpretive robustness, favouring disclosure primarily when findings are clearly actionable and clinically reliable, and expressing greater caution toward variants with limited or uncertain utility.\u003c/p\u003e \u003cp\u003eThese tensions echo international debates on scope expansion, where arguments for broader inclusion often rely on the absence of alternative screening opportunities, potential reproductive counselling benefits, or reduction of diagnostic delay, while counterarguments are linked to the risks of disclosing late-onset or uncertain during the vulnerability of the neonatal period\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e. Staged or two-step strategies have been proposed as possible compromises between these positions.\u003c/p\u003e \u003cp\u003eBeyond questions of scope, our findings also reveal systemic ambivalence toward genomic integration. Interest in diagnostic potential coexisted with concerns about the capacity to absorb and act upon large-scale genomic data for all newborns, including infrastructure limitations, insufficient specialised training, lack of standardised protocols, and the need for ethical alignment. These findings suggest that genomic expansion is not merely a technological shift but a systemic one, requiring reinforced training for paediatricians, midwives, gynaecologists and primary care physicians, investment in bioinformatics support, coordinated variant interpretation frameworks, and robust governance structures. Without such preparation, expansion may increase inequities and strain specific sectors of the healthcare system.\u003c/p\u003e \u003cp\u003eThe management of VUS emerged as particularly complex. While NBS professionals are accustomed to uncertainty in metabolic screening, where follow-up testing is available and benefits clearly outweigh harms, genomic expansion introduces uncertainty across a broader range of diseases, often without orthogonal confirmatory tests. In this setting, the benefit\u0026ndash;harm balance becomes more difficult to establish. Many respondents viewed non-disclosure of VUS as a reasonable boundary condition for expansion, especially given expectations that interpretive precision may improve over time.\u003c/p\u003e \u003cp\u003eInformation practices appeared as a central condition of acceptability. Many professionals considered current parental information insufficient and reported limited preparedness to manage genomic results. While earlier and more structured communication was supported, fully individualised decision-making was viewed as difficult in routine settings. These findings reinforce calls for nationally coordinated information strategies in any genomic extension\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eInternational research reports similar patterns, including stronger support for actionable childhood conditions, greater caution among genetic specialists, and concerns regarding counselling resources, consent, operational feasibility, and scope definition. Reviews synthesising these studies indicate that while gNBS is increasingly considered plausible, its legitimacy depends on balancing clinical utility, parental autonomy, and system capacity. When compared with parental perspectives, clinicians tend to express greater concern regarding privacy, discrimination, data governance, and long-term uncertainty, whereas parents more often emphasise potential benefit and reassurance\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e,\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e. Similar patterns were observed in the SeDeN-p3 study\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eSeveral limitations must be acknowledged. Voluntary participation may have introduced selection bias, and findings should not be interpreted as reflecting national prevalence of opinions. The survey was conducted in 2021, when gNBS remained largely prospective; subsequent therapeutic advances pilot initiatives may have influenced professional views. Technical complexity and heterogeneous familiarity with genetics across professional groups likely contributed to self-reported limited expertise among many respondents, suggesting that some answers may reflect uncertainty rather than fixed positions. In particular, low support for exome or genome sequencing should be interpreted cautiously, as these terms may have been perceived as implying unrestricted analysis, rather than targeted approaches.\u003c/p\u003e \u003cp\u003eSince data collection, several expanded NBS initiatives have moved into pilot or real-world research phases. Evidence emerging from these experiences, as synthesised in recent reviews\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e,\u003cspan additionalcitationids=\"CR25 CR26 CR27 CR28 CR29 CR30 CR31 CR32 CR33 CR34 CR35 CR36 CR37 CR38 CR39 CR40 CR41\" citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e\u003c/sup\u003e, will be essential to refine genomic screening strategies in practice. Parallel collaborative efforts, including the \u003cem\u003eInternational Consortium on Newborn Sequencing\u003c/em\u003e (ICoNS) [URL can further support this professional learning process by enabling cross-site comparisons and deliberation on shared challenges such as gene list definition, consent models, data governance, and public health integration\u003csup\u003e\u003cspan additionalcitationids=\"CR44 CR45 CR46 CR47 CR48\" citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e\u003c/sup\u003e. Updated lists of treatable rare genetic diseases are also being developed to inform policy and clinical decision-making and to provide a transparent basis for professional discussion, training, and guideline development\u003csup\u003e\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eData Availability Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eURL\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInternational Consortium on Newborn Sequencing (ICoNS) : https://www.iconseq.org/the-consortium\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors thank all healthcare professionals who participated in the study and the professional networks that supported the dissemination of the survey. In this contex, they are particularly grateful to the \u003cem\u003eInter Fili\u0026egrave;res de Sant\u0026eacute; Maladies Rares\u003c/em\u003e, the \u003cem\u003eAssociation Francophone de G\u0026eacute;n\u0026eacute;tique Clinique\u003c/em\u003e, and the \u003cem\u003eSoci\u0026eacute;t\u0026eacute; Fran\u0026ccedil;aise de M\u0026eacute;decine Pr\u0026eacute;dictive et Personnalis\u0026eacute;e\u003c/em\u003e for facilitating the distribution of the survey within their networks. The authors also acknowledge ADN Soft for their support in data management and analysis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCL (Camille Level), LF (Laurence Faivre), ML (Margot Lemaitre), DS (Dominique Salvi), CTR (Christel Thauvin-Robinet), FH (Fr\u0026eacute;d\u0026eacute;ric Huet), CP (Christine Peyron)\u003c/p\u003e\n\u003cp\u003eCL conceived and designed the study, coordinated recruitment, supervised data management, conducted statistical and qualitative analyses, and drafted the first manuscript. CP and LF contributed to study design, defined objectives and hypotheses, supported interpretation of results, and provided substantial revisions. CTR and FH contributed to the development of the study protocol and questionnaire. DS supported recruitment organisation, data collection logistics, and data preparation. ML contributed to qualitative analysis. All authors critically reviewed the manuscript and approved the final version.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by contributions from Pfizer and Kyowa Kirin Pharma. These organisations had no role in the conceptualisation, conduct, analysis or writing of the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAccording to French regulations governing non-interventional survey-based research involving healthcare professionals, formal ethical committee approval was not required. The study complied with applicable data protection regulations. All participants received information about the study and provided electronic informed consent prior to participation. Responses were collected anonymously.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eRemec ZI \u003cem\u003eet al.\u003c/em\u003e Next-Generation Sequencing in Newborn Screening: A Review of Current State. \u003cem\u003eFront Genet\u003c/em\u003e 2021; 12. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3389/fgene.2021.662254\u003c/span\u003e\u003cspan address=\"10.3389/fgene.2021.662254\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWoerner AC, Gallagher RC, Vockley J, Adhikari AN. 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Universal newborn screening using genome sequencing: early experience from the GUARDIAN study. \u003cem\u003ePediatr Res\u003c/em\u003e 2024;: 1\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZiegler A \u003cem\u003eet al.\u003c/em\u003e Expanded Newborn Screening Using Genome Sequencing for Early Actionable Conditions. \u003cem\u003eJAMA\u003c/em\u003e 2025; 333: 232\u0026ndash;240.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBoemer F \u003cem\u003eet al.\u003c/em\u003e Population-based, first-tier genomic newborn screening in the maternity ward. \u003cem\u003eNat Med\u003c/em\u003e 2025; 31: 1339\u0026ndash;1350.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRahman S, Bick D, Scott RH. 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Age-Based Genomic Screening during Childhood: Ethical and Practical Considerations in Public Health Genomics Implementation. \u003cem\u003eInt J Neonatal Screen\u003c/em\u003e 2023; 9: 36.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDownie L \u003cem\u003eet al.\u003c/em\u003e Gene selection for genomic newborn screening: moving towards consensus? \u003cem\u003eGenet Med\u003c/em\u003e 2024;: 101077.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHorton R \u003cem\u003eet al.\u003c/em\u003e Challenges of using whole genome sequencing in population newborn screening. \u003cem\u003eBMJ\u003c/em\u003e 2024; 384: e077060.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMinten T \u003cem\u003eet al.\u003c/em\u003e Data-driven consideration of genetic disorders for global genomic newborn screening programs. \u003cem\u003eMedRxiv Prepr Serv Health Sci\u003c/em\u003e 2025;: 2024.03.24.24304797.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGreen RC \u003cem\u003eet al.\u003c/em\u003e Actionability of unanticipated monogenic disease risks in newborn genomic screening: Findings from the BabySeq Project. \u003cem\u003eAm J Hum Genet\u003c/em\u003e 2023; 110: 1034\u0026ndash;1045.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBick D, Bick SL, Dimmock DP, Fowler TA, Caulfield MJ, Scott RH. An online compendium of treatable genetic disorders. \u003cem\u003eAm J Med Genet C Semin Med Genet\u003c/em\u003e 2021; 187: 48\u0026ndash;54.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eURL\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eInternational Consortium on Newborn Sequencing (ICoNS): \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.iconseq.org/the-consortium\u003c/span\u003e\u003cspan address=\"https://www.iconseq.org/the-consortium\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"european-journal-of-human-genetics","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"ejhg","sideBox":"Learn more about [European Journal of Human Genetics](http://www.nature.com/ejhg/)","snPcode":"41431","submissionUrl":"https://mts-ejhg.nature.com/cgi-bin/main.plex","title":"European Journal of Human Genetics","twitterHandle":"@ejhg_journal","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Expanded newborn screening, Genomic sequencing, Professional acceptability, Quantitative studies","lastPublishedDoi":"10.21203/rs.3.rs-8743981/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8743981/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eTherapeutic advances and the rapid, cost-effective development of next-generation sequencing (NGS) have increased interest in expanding newborn screening (NBS) through genomics. The SeDeN-p2 study assessed the acceptability among healthcare professionals in France, of expanding NBS, particularly through the use of genetics as a first-line test, by examining areas of convergence and divergence in their expectations.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA national cross-sectional survey was conducted between June and December 2021 via professional networks and learned societies involved in NBS and genetics, in partnership with the French Society of Newborn Screening. The questionnaire comprised 101 closed-ended and 14 open-ended questions. After data cleaning, 1,077 responses were analysed.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eRespondents were mainly paediatricians (44%), gynaecologists or midwives (38%), and medical geneticists (18%). There was near-unanimous support for including treatable childhood disorders, with over 95% endorsing their integration into NBS, although 29% still considered the current NBS programme sufficient. Views varied substantially by specialty, particularly regarding the scope of conditions and the use of NGS. Genetics professionals were more conservative, especially concerning variants with limited actionability, organisational constraints, and interpretive uncertainty, while midwives and gynaecologists were generally more favourable. Convergence was strongest for treatable paediatric disorders and shared ethical concerns, notably data misuse, psychosocial burden, and the child\u0026rsquo;s future autonomy. The need for improved communication with families was widely emphasised.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThe SeDeN-p2 study shows strong but conditional support among French healthcare professionals for integrating genetics into NBS, providing key insights to inform future policy and practice.\u003c/p\u003e","manuscriptTitle":"Healthcare Professionals’ Views on Expanding Newborn Screening with or without Genomics in France: Results of the SeDeN-p2 Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-27 12:07:00","doi":"10.21203/rs.3.rs-8743981/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"This content is not available.","date":"2026-04-16T08:52:04+00:00","index":3,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2026-03-24T13:53:13+00:00","index":3,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2026-03-23T23:40:12+00:00","index":2,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2026-03-09T15:07:10+00:00","index":1,"fulltext":"This content is not available."},{"type":"reviewersInvited","content":"","date":"2026-02-24T14:04:04+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-02-23T12:06:43+00:00","index":"","fulltext":""},{"type":"submitted","content":"European Journal of Human Genetics","date":"2026-02-23T11:57:21+00:00","index":"","fulltext":""},{"type":"checksFailed","content":"","date":"2026-02-03T16:27:07+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-01-30T18:00:55+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"european-journal-of-human-genetics","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"ejhg","sideBox":"Learn more about [European Journal of Human Genetics](http://www.nature.com/ejhg/)","snPcode":"41431","submissionUrl":"https://mts-ejhg.nature.com/cgi-bin/main.plex","title":"European Journal of Human Genetics","twitterHandle":"@ejhg_journal","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"f0256d95-fc81-4afd-aec8-538d8f41785f","owner":[],"postedDate":"February 27th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":63377588,"name":"Scientific community and society/Social sciences/Economics"},{"id":63377589,"name":"Health sciences/Health care/Paediatrics"}],"tags":[],"updatedAt":"2026-02-27T12:07:00+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-27 12:07:00","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8743981","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8743981","identity":"rs-8743981","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}