European survey of newborn bloodspot screening for CF: opportunity to address challenges and improve performance

Anne Munck; Daria O Berger; Kevin W Southern; Carla Carducci; Karin M de Winter-de Groot; Silvia Gartner; Nataliya Kashirskaya; Barry Linnane; Marijke Proesmans; Dorota Sands; Olaf Sommerburg; Carlo Castellani; Jürg Barben; European CF Society Neonatal Screening Working Group (ECFS NSWG)

doi:10.1016/j.jcf.2022.09.012

European survey of newborn bloodspot screening for CF: opportunity to address challenges and improve performance

J Cyst Fibros. 2023 May;22(3):484-495. doi: 10.1016/j.jcf.2022.09.012. Epub 2022 Nov 10.

Collaborators

European CF Society Neonatal Screening Working Group (ECFS NSWG):
Sabine Renner¹⁴, Max Zeyda¹⁴, Elke de Wachter¹⁵, Luc Regal¹⁶, Felix Votava¹⁷, Andrea Holubova¹⁸, Marianne Skov¹⁹, Tessa Morgan²⁰, Paul Bregeaut²¹, Loretta O'Grady²², Ines Bucci²³, Stefano Pantano²⁴, Simonetta Simonetti²⁵, Domenica De Venuto²⁶, Donatello Salvatore²⁷, Nicola Perrotti²⁸, Mimma Caloiero²⁹, Giuseppe Castaldo³⁰, Antonella Tosco³¹, Francesca Righetti³², Giovanna Pisi³³, Fiorella Battistini³⁴, Antonio Angeloni³⁵, Giuseppe Cimino³⁶, Giovanni Fiocchi³⁷, Antonella Angiolillo³⁸, Michela Cassanello³⁹, Luisella Alberti⁴⁰, Laura E Claut⁴¹, Raffaele Badolato⁴², Enza Pavanello⁴³, Benedetta Fabrizzi⁴⁴, Elisabetta Bignamini⁴⁵, Anna Cardillo⁴⁶, Mariangela Lombardo⁴⁷, Letizia Cocciadiferro⁴⁸, Lisa Termini⁴⁹, Daniela Dolce⁵⁰, Vito Terlizzi⁵¹, Anna Tamanini⁵², Francesca Pauro⁵³, Giancarlo la Marca⁵⁴, Elina Aleksejeva⁵⁵, Dita Gaidule-Logina⁵⁶, Stoika Fustik⁵⁷, Violeta Anastasovska⁵⁸, Marelle Bouva⁵⁹, Alastair Reid⁶⁰, Jennifer Cundick⁶¹, Emma Lundman⁶², Egil Bakkeheim⁶³, Katarzyna Zybert⁶⁴, Mariusz Oltarzewski⁶⁵, Laura Vilarinho⁶⁶, Victoria Sherman⁶⁷, Elena Kondratyeva⁶⁸, Sarah Smith⁶⁹, Gordana Vilotijevic Dautovic⁷⁰, Maria Knapkova⁷¹, Zuzana Mydlova⁷², Rosa Mª López⁷³, Valle Velasco⁷⁴, Felicitas Díaz Flores⁷⁵, Cristóbal Colón Mejeras⁷⁶, Eva Sl Pedersen⁷⁷, Ugur Ozcelik⁷⁸, Bulent Karadag⁷⁹, Halyna Makukh⁸⁰, Moat Stuart⁸¹

Affiliations

¹ Hospital Necker Enfants-Malades, AP-HP, CF centre, Université Paris Descartes, France, and CF referent physician for the French Society of Newborn Screenings.
² ECFS NSWG Data Manager, Institute of Social and Preventive Medicine and Graduate School for Health Sciences, University of Bern, Switzerland.
³ Department of Women's and Children's Health, University of Liverpool, United Kingdom.
⁴ Department of Experimental Medicine, Sapienza University, Rome Italy.
⁵ Department of Paediatric Pulmonology & Allergology, Wilhelmina Children's Hospital/University Medical Centre Utrecht, Utrecht University, Utrecht, the Netherlands.
⁶ Pediatric Pulmonology and Cystic Fibrosis Unit, Hospital Universitari Vall d´Hebron, Barcelona, Spain.
⁷ Laboratory of genetic epidemiology, Research Centre for Medical Genetics/Moscow Regional Research and Clinical Institute, Moscow, Russian Federation.
⁸ Graduate Entry Medical School and Centre for Interventions in Infection, Inflammation & Immunity (4i), University of Limerick, Limerick, Ireland.
⁹ Division of Woman and Child, Department of Pediatrics, University Hospitals Leuven, Leuven, Belgium.
¹⁰ Cystic Fibrosis Department, Institute of Mother and Child, Warsaw, Poland.
¹¹ Paediatric Pulmonology, Allergology & CF Centre, Department of Paediatrics III, and Translational Lung Research Center, German Lung Research Center, University Hospital Heidelberg, Germany.
¹² IRCCS Istituto Giannina Gaslini, Cystic Fibrosis Center, Genoa, Italy.
¹³ Paediatric Pulmonology & CF Centre, Children's Hospital of Eastern Switzerland, St. Gallen, Switzerland. Electronic address: [email protected].
¹⁴ Medical University Vienna, Vienna, Austria.
¹⁵ Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium.
¹⁶ Flemish Center Brussels for Newborn Screening Brussels (VCBMA), Belgium.
¹⁷ National Coordination Centre for Newborn Screening, General University Hospital, Prague, Czech Republic.
¹⁸ National Coordination Centre for Newborn Screening, General University Hospital, Prague, Czech Republic.
¹⁹ Department of Pediatrics, CF Center Copenhagen, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
²⁰ NHS Newborn Blood Spot Screening Programme, Public Health England Screening, England.
²¹ Centre National de Coordination du Dépistage Néonatal, CHRU de Tours, France.
²² Newborn Blood Spot Screening Laboratory, Dublin 1, Ireland.
²³ Newborn Screening Laboratory, Center for Advanced Studies and Technology (CAST), "G. d'Annunzio" University of Chieti Pescara, Italy.
²⁴ Centro regionale per la fibrosi cistica, Ospedale San Liberatore, Viale Risorgimento, Atri, Italy.
²⁵ Centro Regionale Screening Neonatale Ospedale Pediatrico Giovanni XXIII Policlinico Bari, Laboratorio di Fibrosi Cistica - U.O.C. Laboratorio di Genetica Medica - A.O.U.C. Policlinico di Bari, Italy.
²⁶ Centro Regionale Screening Neonatale Ospedale Pediatrico Giovanni XXIII Policlinico Bari, Italy.
²⁷ Centro regionale per la fibrosi cistica, Ospedale San Carlo, Potenza, Italy.
²⁸ Unità Operativa di Genetica Medica Centro Regionale di Screening Neonatale, Catanzaro, Italy.
²⁹ Centro regionale per la fibrosi cistica, Ospedale "Giovanni Paolo II", Lamezia Terme, Italy.
³⁰ Laboratorio Di Screening Neonatale della Fibrosi Cistica, Napoli, Italy.
³¹ Centro di riferimento regionale per la fibrosi cistica, Azienda ospedaliera-universitaria "Federico II", Napoli, Italy.
³² Centro Laboratoristico Regionale di Riferimento per lo Screening Neonatale e Malattie Endocrino-Metaboliche, Bologna, Italy.
³³ Centro regionale di riferimento per la diagnosi e cura della fibrosi cistica di Parma, Azienda Ospedaliero-Universitaria di Parma, Italy.
³⁴ Centro regionale di riferimento per la diagnosi e cura della fibrosi cistica, Ospedale Maurizio Bufalini, Cesena, Italy.
³⁵ Laboratorio di Screening Neonatale e conferma diagnostica, Roma, Italy.
³⁶ Centro di riferimento regionale per la fibrosi cistica, Umberto I - Policlinico di Roma, Roma, Italy.
³⁷ Centro per la fibrosi cistica, Ospedale pediatrico Bambino Gesù, Roma, Italy.
³⁸ Centro territoriale di riferimento aziendale per la fibrosi cistica, Ospedale Antonio Cardarelli Campobasso, Italy.
³⁹ LABSIEM (Laboratory for the Study of Inborn Errors of Metabolism) Pediatric and Endocrinology, IRCCS Istituto Giannina, Genova, Italy.
⁴⁰ Regional Reference Laboratory for Newborn Screening "Ospedale dei Bambini V. Buzzi", ASST Fatebenefratelli Sacco, Milano, Italy.
⁴¹ Cystic Fibrosis Center, Fondazione IRCCS ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
⁴² Centro regionale di supporto per la fibrosi cistica, Azienda Ospedaliera Spedali Civili di Brescia, Brescia, Italy.
⁴³ Città della Salute e della Scienza di Torino, S.C. Biochimica Clinica, S.S. Laboratorio di screening prenatale e neonatale, Torino, Italy.
⁴⁴ Centro Fibrosi Cistica, Ospedali Riuniti Ancona, Ancona, Italy.
⁴⁵ Centro regionale di riferimento per la fibrosi cistica Ospedale Infantile Regina Margherita, Sant' Anna, Torino, Italy.
⁴⁶ laboratorio di screening neonatale esteso A.O.U. Policlinico "G.Rodolico - S. Marco", Catania, Italy.
⁴⁷ Centro HUB Fibrosi Cistica, Messina, Italy.
⁴⁸ CSN Sicilia Occidentale Ospedale Pediatrico G.Di Cristina, Palermo, Italy.
⁴⁹ CRR Servizio per la diagnosi la cura della fibrosi cistica, Arnas Civico-Presidio G.di Christina, Palermo, Italy.
⁵⁰ Laboratorio Centro Regionale Toscano per la Fibrosi Cistica, Dipartimento specialistico interdisciplinare, Azienda Ospedaliero Universitaria Meyer, Firenze, Italy.
⁵¹ Cystic Fibrosis Regional Reference Center, Department of Paediatric Medicine, Anna Meyer Children's University, Florence, Italy.
⁵² Service of Laboratory Medicine, Section of Molecular Pathology, University Hospital of Verona, Italy.
⁵³ Cystic Fibrosis Center, Azienda Ospedaliera Univesitaria Integrata, Verona, Italy.
⁵⁴ Department of Experimental and Clinical Biomedical Sciences, University of Florence and Newborn Screening, Clinical Chemistry and Pharmacology Lab, Meyer Children's University Hospital, Florence, Italy.
⁵⁵ Dept of Pneumology, Children's Clinical University Hospital, Rīga Stradinš University, Riga, Latvia.
⁵⁶ CF Centre, Children's Clinical University Hospital, Latvia.
⁵⁷ Centre for Cystic Fibrosis, University Children's Hospital, Skopje, North Macedonia.
⁵⁸ University Clinic for Pediatrics, Department for Neonatal Screening, North Macedonia.
⁵⁹ Center for Health protection, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
⁶⁰ Royal Belfast Hospital for Sick Children, Belfast Health and Social Care Trust, Belfast, North Ireland, UK.
⁶¹ Regional Blood Spot Screening Laboratory and Child Health Systems, Northern Ireland, UK.
⁶² Norwegian National Unit for Newborn Screening, Women and Children's Division, Oslo University Hospital, Norway.
⁶³ Norwegian Resource Centre for Cystic Fibrosis, Women and Children's Division, Oslo University Hospital HF, Oslo, Norway.
⁶⁴ Cystic Fibrosis Department, Institute of Mother and Child, Warsaw, Poland.
⁶⁵ Department of screening and metabolic diagnostic, Institute of Mother and Child, Warsaw, Poland.
⁶⁶ Newborn Screening, Metabolism & Genetics Unit, National Institute of Health Dr Ricardo Jorge, Porto, Portugal.
⁶⁷ Department of Cystic fibrosis, Research Centre for Medical Genetics, Moscow, Russian Federation.
⁶⁸ Research Centre for Medical Genetics, Moscow, Russian Federation.
⁶⁹ Director of Scottish Newborn Screening Laboratory, Glasgow, Scotland, UK.
⁷⁰ Institute for Child and youth Health care of Vojvodina, Medical Faculty, University of Novi Sad, Vojvodina, Serbia.
⁷¹ Laboratory of Newborn Screening Centre Slovak Republik, Children´s University Hospital Banska Bystrica, Slovakia.
⁷² Laboratory of Newborn Screening Centre Slovak Republik, Children´s University Hospital Banska Bystrica, Slovakia.
⁷³ Laboratorio de Cribado Neonatal Servicio de Bioquímica y Genética Molecular. Hospital Clínic. Barcelona, Spain.
⁷⁴ Cribado neonatal de metabolopatías congénitas del recién nacido de Canarias, Unidad de Metabolopatías: Laboratorio Central, Complejo Hospitalario Universitario de Canarias, Tenerife, Spain.
⁷⁵ Cribado neonatal del recién nacido de Canarias, Unidad de Metabolopatías: Laboratorio Central, Tenerife, Spain.
⁷⁶ Unidade de Diagnóstico e Tratamento das Enfermidades Metabólicas Conxénitas. Centro de Referencia Español (CSUR) y Europeo (MetabERN), Galicia, Spain.
⁷⁷ Institute of Social and Preventive Medicine, University of Bern, Switzerland.
⁷⁸ Hacettepe University, Division of Pediatric Pulmonology, Ankara, Turkey.
⁷⁹ Marmara University, Division of Pediatric Pulmonology, Istanbul, Turkey.
⁸⁰ Institute of Hereditary Pathology, Ukrainian National Academy of Medical Sciences, Lviv, Ukraine.
⁸¹ Wales Newborn Screening Laboratory, Medical Biochemistry, University Hospital of Wales, Cardiff, UK.

PMID: 36372700
DOI: 10.1016/j.jcf.2022.09.012

Abstract

Background: The aim of this study was to record the current status of newborn bloodspot screening (NBS) for CF across Europe and assess performance.

Methods: Survey of representatives of NBS for CF programmes across Europe. Performance was assessed through a framework developed in a previous exercise.

Results: In 2022, we identified 22 national and 34 regional programmes in Europe. Barriers to establishing NBS included cost and political inertia. Performance was assessed from 2019 data reported by 21 national and 21 regional programmes. All programmes employed different protocols, with IRT-DNA the most common strategy. Six national and 11 regional programmes did not use DNA analysis.

Conclusions: Integrating DNA analysis into the NBS protocol improves PPV, but at the expense of increased carrier and CFSPID recognition. Some programmes employ strategies to mitigate these outcomes. Programmes should constantly strive to improve performance but large datasets are needed to assess outcomes reliably.

Keywords: CFSPID, carriers; CFTR gene analysis; Cystic fibrosis; IRT; Newborn bloodspot screening; PAP.

MeSH terms

Cystic Fibrosis Transmembrane Conductance Regulator / genetics
Cystic Fibrosis* / diagnosis
Cystic Fibrosis* / genetics
Genetic Testing* / methods
Humans
Infant, Newborn
Neonatal Screening / methods
Trypsinogen

Substances

Cystic Fibrosis Transmembrane Conductance Regulator
Trypsinogen