System Maintenance Notice

Please note that maintenance work is scheduled between 4 AM and 5 AM - CET. During this time, you may experience reduced performance. Thanks for your patience.

Publications

Journal Article Epublish

PubMed: 42359128 DOI: 10.3389/fpubh.2026.1822461

European Reference Networks as core health structures where referring genetic newborn screening positive infants: an innovative operational research framework.

Front Public Health 14:1822461

Authors: Fernanda Fortunato, Rita Selvatici, Jan Kirschner, Stefaan Sansen, Emanuele Agolini, Silvia Ottombrino, Enrico Bertini, Antonio Novelli, Moshe Einhorn, Leslie Matalonga, Sergi Beltran, Ivo G Gut, Alberto M Pereira, Olaf Hiort, Franz Schaefer, Alain Verloes, Ansgar W Lohse, Arthur A M Wilde, Christine Bodemer, Guillaume Jondeau, Hélène Dollfus, Holm Graessner, Irene M J Mathijssen, Ikram L'khssim, Jean-Yves Blay, Luca Sangiorgi, Pierre Fenaux, María Del Mar Mañú Pereira, Victoria Gutiérrez Valle, Marta Mosca, Nicoline Hoogerbrugge, Rene Wijnen, Teresinha Evangelista, Carla D'Angelo, Thomas O F Wagner, Wout F J Feitz, Ruth Ladenstein, Zoltan Dobai, Nico Wulffraat, Nicola Ruperto, Paloma Jara Vega, Cinzia Maria Bellettato, Maurizio Scarpa, Michela Onali, Sébile Tchaicha, Alexis Arzimanoglou, Jun Oh, Dominic Lenz, Birute Tumiene, Aldona Zygmunt … and 1 other author

Affiliations

  • Unit of Medical Genetics, Department of Medical Sciences, University of Ferrara, Ferrara, Italy.
  • Department of Mother and Child, University Hospital S. Anna, Ferrara, Italy.
  • Department of Neuropediatric and Muscle Disorders, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
  • Sanofi, Diegem, Belgium.
  • Laboratory of Medical Genetics, Translational Cytogenomics Research Unit & Research Unit of Neuromuscular Disorders, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
  • Genoox, Tel Aviv, Israel.
  • Centro Nacional de Análisis Genómico (CNAG), Barcelona, Spain.
  • Department of Endocrinology and Metabolism, Amsterdam UMC, Location University of Amsterdam, Amsterdam, Netherlands.
  • Division of Pediatric Endocrinology and Diabetes, Department of Pediatric and Adolescent Medicine, University of Lübeck, Lübeck, Germany.
  • Center of Pediatric and Adolescent Medicine, University of Heidelberg, Heidelberg, Germany.
  • Department of Genetics, APHP-Robert Debré University Hospital, Université de Paris, Paris, France.
  • Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
  • Department of Clinical Cardiology, Heart Center, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands.
  • Department of Dermatology, Necker Enfants Malades Hospital, AP-HP Center-Paris University, Paris, France.
  • Hospital Bichat-Claude Bernard, APHP, Université Paris Cité, Paris, France.
  • Institut de Génétique Médicale d'Alsace, University Hospital of Strasbourg and Strasbourg University, Strasbourg, France.
  • Centre for Rare Diseases and Institute for Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany.
  • Department of Plastic and Reconstructive Surgery and Hand Surgery, Erasmus University Medical Center, Rotterdam, Netherlands.
  • Centre Léon Bérard, Université Claude Bernard Lyon I, and Center de Recherche en Cancérologie de Lyon, Lyon, France.
  • Department of Rare Skeletal Disorders, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy.
  • Saint Louis Hospital, Paris Cité University, Paris, France.
  • Group of Translational Research in Cancer and Blood disorders in Children, Rare Anemia Disorders Research Laboratory, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain.
  • Rheumatology Unit, Azienda Ospedaliero Universitaria Pisana and University of Pisa, Pisa, Italy.
  • Department of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands.
  • Department of Pediatric Surgery, Erasmus MC Sophia Children's Hospital, Rotterdam, Netherlands.
  • Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris (APHP), Paris, France.
  • University Hospital Frankfurt, Frankfurt, Germany.
  • Department of Urology, Radboud University Medical Center Amalia Children's Hospital, Nijmegen, Netherlands.
  • Department of Pediatrics, St. Anna Children's Hospital and St Anna Children's Cancer Research Institute, Medical University of Vienna, Vienna, Austria.
  • Department of Pediatric Rheumatology and Immunology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.
  • UOC Reumatologia e Malattie Autoinfiammatorie, IRCCS Istituto G. Gaslini, Genova, Italy.
  • Department of Pediatric Hepatology, La Paz University Hospital, Molecular Hepatology Group, La Paz Institute of Biomedical Research (IdiPAZ), Madrid, Spain.
  • Regional Coordinating Center for Rare Diseases, Udine University Hospital, Udine, Italy.
  • ERN EURO-NMD Patient Advisory Board, Paris, France.
  • Hospital Sant Joan de Déu, Barcelona, Spain.
  • Department of Pediatric Nephrology, Medical University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
  • Division of Pediatric Neurology and Metabolic Medicine, Center for Child and Adolescent Medicine, Medical Faculty, University Hospital Heidelberg, Heidelberg University, Heidelberg, Germany.
  • Faculty of Medicine, Institute of Biomedical Sciences, Vilnius University, Vilnius, Lithuania.
  • Pfizer Inc. Collegeville, Pennsylvania, PA, United States.

Abstract

Rare diseases (RDs), affecting fewer than 5 people per 10,000, present unique challenges to usual care pathways due to their unique characteristics: rarity and large number of disease entities, heterogeneous clinical manifestations and genetic causes, multisystemic involvement, and high complexity of diagnosis and treatment. This complexity often hampers the setting of appropriate pathways of care, which are not easily identifiable by patients and stakeholders. This ultimately leads to significant delays in diagnosis, lack of timely access to RD treatments and profound inequalities across countries. To overcome these difficulties, European Reference Networks (ERNs) were established in 2017 to facilitate patients' referral to expertise and excellent services, aiming to reduce disparities and expedite diagnosis, standard of care, and treatment for people living with rare diseases (PLWRDs). Since 72% of rare diseases are of genetic in origin and mostly affect children, genomic newborn screening (gNBS) offers a powerful tool to overcome diagnostic barriers by providing early and accurate genetic diagnoses for a wide range of treatable pediatric RDs. Several gNBS initiatives have been implemented across Europe and worldwide. Screen4Care (S4C) is an EU-IHI funded research project integrating gNBS with artificial intelligence (AI)-based tools to improve care for PLWRDs in the EU. The project will offer gNBS to up to 18,000 infants using a capture-based panel (TREAT-panel) targeting 245 genes associated with treatable genetic disorders [ClinicalTrials.gov NCT06549218]. Within this framework, an operational pipeline and a comprehensive step-by-step process in collaboration with ERNs were developed to refer gNBS-positive newborns to the appropriate ERN, ensuring timely access to optimal standards of care and available treatments. We suggest that this organisational and structured health model might be adopted by EU Member States (MS), as it provides a defined clinical framework for identifying newborns with RDs at birth and ensuring they receive the correct care, thereby promoting patient-centred and equitable disease management.

MeSH

Operations Research, Infant, Newborn, Rare Diseases, Neonatal Screening, Public Health, Diagnosis, Research, Therapeutics, Artificial Intelligence, Infant