Lars Neth

Definition of problem Newborn screening (NBS) is an internationally successful program for the secondary prevention of rare congenital diseases. At present, most of the target conditions in NBS are diagnosed by biochemical markers. Recent advances in genomic sequencing and in the bioinformatic evaluation of genetic variants will soon make it feasible however to expand NBS significantly by testing newborns directly for pathogenic variants. Yet, genomic newborn screening (gNBS) raises important ethical issues that require resolution, given that several pilot studies on gNBS implementation are already underway. Given a rapidly growing scholarly engagement with the ethics of gNBS, a more systematic and comprehensive mapping of the ethical issues and considerations relevant to gNBS is needed to move the debate forward at this point. Methods In this integrative review, we survey the literature with the aim of delineating a conceptual framework for the ethics of gNBS, which organizes the ongoing debate and thereby provides guidance for further research. Here in Part II, we outline a tentative normative framework for the ethics of gNBS by systematizing the core ethical principles advanced in the literature and offer an original contribution to the debate beyond a mere survey of considerations by proposing a substantive interpretation of these principles and how they relate to each other in the gNBS context. We demonstrate the general utility of this framework for addressing the ethical issues involved in gNBS program design by drawing out its implications for some of the issues presented in Part I. Conclusion In Part I, we formulated a requirement of informed consent for gNBS. Since newborns still lack a capacity for autonomous choice and informed consent, we approach gNBS program design through the question of what renders it ethically permissible for the child’s custodians to consent to gNBS in its name. Consequently, we discuss the authority of parents as surrogate decision-makers for their child, who are bound by a duty of care towards it. We substantiate this duty (a) by discussing several rights of the child, viz., its rights to informational self-determination, genetic ignorance, privacy, and an open future, and (b) by developing a specification of the best interest standard for children as the main principle that should guide and constrain both parental decision-making and gNBS program design. Finally, we consider concerns that gNBS could result in a harmful medicalization of healthy children.

Definition of problem Newborn screening (NBS) is an internationally successful program for the secondary prevention of rare congenital diseases. At present, most of the target conditions in NBS are diagnosed by biochemical markers. Recent advances in genomic sequencing and in the bioinformatic evaluation of genetic variants will soon make it feasible however to expand NBS significantly by testing newborns directly for pathogenic variants. Yet, genomic newborn screening (gNBS) raises important ethical issues that require resolution, given that several pilot studies on gNBS implementation are already underway. Given a rapidly growing scholarly engagement with the ethics of gNBS, a more systematic and comprehensive mapping of the ethical issues and considerations relevant to gNBS is needed to move the debate forward at this point. - Methods In this integrative review, we survey the literature with the aim of delineating a conceptual framework for the ethics of gNBS, which organizes the ongoing debate and thereby provides guidance for further research. Here in Part I, we focus primarily on an exposition of the ethical issues and questions involved in gNBS program design. - Conclusion The ethical issues divide into issues regarding (1) the test itself and the selection of target conditions, (2) informed consent, and (3) genomic data generation, storage, and use. Regarding (1) we discuss several dimensions along which potential target conditions can differ and their ethical implications, and formulate some requirements on appropriate selection criteria with special regard to minimizing diagnostic and therapeutic uncertainty. Regarding (2) we discuss the need for informed consent, the structure and content of pre-test counseling (when, who, what, how), the suggestion of a tiered testing offer, and familial conflict. Regarding (3) we discuss liberal versus restrictive approaches to genomic data generation, parental consent to genomic raw data storage for further uses beyond the test, some candidate further uses, and the risk of abuse.

[English version below] Diese Stellungnahme zielt darauf ab, Empfehlungen für akzeptable Rahmenbedingungen eines Genomischen-Neugeborenen-Screening (gNBS)-Programms in Deutschland zu formulieren, darunter Empfehlungen zu Auswahlkriterien für Zielkrankheiten und zum Management eines gNBS-Programms sowie zur gesetzlichen Neuregulierung. Sie ist Ergebnis eines dreijährigen Forschungsprojektes, das an den Universitäten Heidelberg und Mannheim durchgeführt wurde. An dem interdisziplinären Projekt beteiligt waren Forscher:innen aus den Bereichen Kinder- und Jugendmedizin, Humangenetik, Rechtswissenschaft, Medizinische Psychologie und Medizinethik sowie Vertreter:innen von Patient:innen-Organisationen (Kindernetzwerk e.V. und Deutsche Interessengemeinschaft Phenylketonurie und verwandte angeborene Stoffwechselstörungen e.V.). Das Projekt wurde vom Bundesministerium für Bildung und Forschung (BMBF; seit 2025 Bundesministerium für Forschung, Technologie und Raumfahrt: BMFTR) gefördert und trägt den Titel NEW_LIVES („Genomic NEWborn screening programs – Legal Implications, Value, Ethics and Society” – „Genomische Neugeborenen-Screening-Programme – Rechtliche Implikationen, Werte, Ethik und Gesellschaft“). Die Stellungnahme beginnt mit einführenden Kapiteln zum Hintergrund des gNBS aus Sicht der verschiedenen Fachbereiche und aus Sicht der Gesellschaft, gefolgt von konkreten Empfehlungen für ein zukünftig mögliches gNBS-Pro- gramm in Deutschland. In der Einleitung (1.) werden erste Ergebnisse bisheriger Forschungsprojekte zum gNBS zusammengefasst und die Zielsetzung und Methode, einschließlich der Rolle von Patient:innen-Vertreter:innen bei der Erarbeitung der Stellungnahme werden beschrieben. In Abschnitt 2 („Medizinischer Hintergrund“) werden Entwicklung, Umfang und Ablauf des derzeitigen Neugeborenen-Screening (NBS)-Programms in Deutschland beschrieben und die Besonderheiten eines gNBS-Programms erläutert. Abschnitt 3 („Perspektive von Patient:innen, Eltern und medizinischem Personal“) fasst die Ergebnisse der sozialempirischen Studien zusammen, die im Rahmen des Projektes NEW_LIVES durchgeführt wurden (Fokusgruppen, bevölkerungs-repräsentative Befragung, querschnittliche Online-Befragung) und vergleicht die Ergebnisse mit anderen, internationalen Studien. Abschnitt 3 enthält außerdem eine gemeinsame Stellungnahme der beiden Patient:innen-Organisationen, die am Projekt NEW_LIVES mitgewirkt haben, zum gNBS. Abschnitt 4 („Genomisches Neugeborenen-Screening aus rechtlicher Sicht“) skizziert den rechtlichen Regulierungsrahmen zum gNBS in Deutschland. Abschnitt 5 („Genomisches Neugeborenen-Screening aus ethischer Sicht“) benennt zentrale ethische Herausforderungen des gNBS und formuliert ethische Orientierungsmaßstäbe für ein zukünftiges gNBS-Programm in Deutschland. Da die Neugeborenen diejenigen sind, die an einem gNBS teilnehmen würden und davon profitieren könnten, stellt deren Kindeswohl den zentralen ethischen Orientierungsmaßstab für die Bewertung dar. Die sich in Abschnitt 6 anschließenden Empfehlungen sind aus Sicht aller an der Erarbeitung dieser Stellungnahme beteiligten Fachdisziplinen und der Patient:innen-Organisationen verfasst Darunter sind einerseits transparente Auswahlkriterien für Zielkrankheiten eines gNBS-Programms (Kriterien 1–11). Andererseits werden Empfehlungen für die Einführung, Qualitätssicherung und Nutzenbewertung eines gNBS-Programms formuliert (Kriterien 12–18). Zudem enthält diese Stellungnahme Empfehlungen zur gesetzlichen Neuregulierung. Eine Publikation der Empfehlungen auf Englisch findet sich in Schnabel-Besson et al.: “A multi-dimensional fra- mework for establishing and managing a genomic newborn screening program” (Arbeitstitel; zum Zeitpunkt des Verfassens dieser Stellungnahme in Vorbereitung; DOI der Preprint-Version: 10.1101/2025.06.17.25329 471). - This position paper has the aim of formulating recommendations for what would be an acceptable framework for a genomic newborn screening (gNBS) programme in Germany, including recommendations for selection criteria for target diseases, and for the management of a gNBS programme, as well as for revision of legislation. It is the result of a research project conducted at the Universities of Heidelberg and Mannheim over the course of three years. This interdisciplinary project brought together researchers from the fields of paediatrics and adolescent medicine, human genetics, law, medical psychology, and medical ethics, as well as representatives of patient organisations (Kindernetzwerk e.V., and Deutsche Interessenge- meinschaft Phenylketonurie und verwandte angeborene Stoffwechselstörungen e.V.). The project was funded by the German Federal Ministry of Education and Research (BMBF; since 2025 Federal Ministry of Research, Technology and Space: BMFTR) and is called NEW_LIVES (“Genomic NEWborn screening programs – Legal Implications, Value, Ethics and Society”). The position paper begins with introductory chapters on gNBS from the perspective of the different disciplines, and from a societal viewpoint, followed by concrete recommendations for a possible future gNBS programme in Germany. The Introduction (1.) summarises the initial results of previous research projects on gNBS, and describes the objectives, and methodology, including the role of patient representatives, in the development of the position paper. Section 2 (“Medical Background”) describes the development, scope, and process of the current NBS programme in Germany, and explains the specific features of a gNBS programme. Section 3 (“Perspectives of Patients, Parents, and Medical Staff”) summarizes the results of the social-empirical studies conducted as part of the NEW_LIVES project (focus groups, population-representative survey, cross-sectional online survey), and compares the results with other, international studies. Section 3 also contains a joint statement on gNBS by the two patient organisations that participated in the NEW_LIVES project. Section 4 (“Genomic Newborn Screening from a Legal Perspective”) outlines the legal regulatory framework for gNBS in Germany. Section 5 (“Genomic Newborn Screening from an Ethical Perspective”) identifies key ethical challenges of gNBS, and formulates ethical guidelines for a future gNBS programme in Germany. Since newborns are the ones who would participate in, and benefit from gNBS, their welfare represents the central ethical guideline for the evaluation. The recommendations in Section 6 are written from the perspective of all disciplines, and patient organisations involved in the development of this position paper. These recommendations reflect the consensus of the inter-, and transdisciplinary group of authors, and form the core of the position paper. They comprise 18 criteria for a possible future gNBS programme in Germany. These include, on the one hand, transparent selection criteria for target diseases of a gNBS programme (criteria 1–11). On the other hand, recommendations are formulated for the introduction, quality assurance, and benefit assessment of a gNBS programme (criteria 12–18). This position paper also contains recommendations for new legal regulations. An English version of the recommendations, including the 11 criteria for selecting target diseases and the 7 criteria for programme management can be found in Schnabel-Besson E, Dikow N, Alex K et al.: “A multidimensional framework for establishing and managing a genomic newborn screening program” (working title; in preparation at the time of writing this position paper; doi of preprint version: 10.1101/2025.06.17.25329471).