Although individual rare disorders are uncommon, it is estimated that, together, 6000+ known rare diseases affect more than 30 million people in Europe, and present a substantial public health burden. Together with the psychosocial burden on affected families, rare disorders frequently, if untreated, result in a low quality of life, disability and even premature death. Newborn screening (NBS) has the potential to detect a number of rare conditions in asymptomatic children, providing the possibility of early treatment and a significantly improved long-term outcome. Despite these clear benefits, the availability and conduct of NBS programmes varies considerably across Europe and, with the increasing potential of genomic testing, it is likely that these differences may become even more pronounced. To help improve the equity of provision of NBS and ensure that all children can be offered high-quality screening regardless of race, nationality and socio-economic status, a technical meeting, endorsed by the Slovenian Presidency of the Council of the European Union, was held in October 2021. In this article, we present experiences from individual EU countries, stakeholder initiatives and the meeting's final conclusions, which can help countries attempting to establish new NBS programmes or expand existing provision.

Center for Inherited Metabolic Diseases Karolinska University Hospital SE 171 76 Stockholm Sweden

Centre for Population Research National Institute for Public Health and the Environment 3720 BA Bilthoven The Netherlands

Department of Biochemistry and Molecular Biology Groupement Hospitalier Est Hospices Civils de Lyon 59 Boulevard Pinel CEDEX 69677 Bron France

Department of Endocrinology Diabetes and Metabolic Diseases University Children's Hospital University Medical Centre Ljubljana Bohoričeva ulica 20 SI 1000 Ljubljana Slovenia

Department of Experimental and Clinical Biomedical Sciences University of Florence 50139 Florence Italy

Department of Molecular Medicine and Surgery Karolinska Institutet SE 171 76 Stockholm Sweden

Department of Pediatrics and Inherited Metabolic Disorders Charles University 1st Faculty of Medicine 12808 Prague Czech Republic

Division of Child Neurology and Metabolic Medicine Center for Child and Adolescent Medicine Heidelberg University Hospital Im Neuenheimer Feld 430 69120 Heidelberg Germany

EURORDIS Rare Diseases Europe 75014 Paris France

Faculty of Medicine University of Ljubljana Vrazov trg 2 SI 1000 Ljubljana Slovenia

General University Hospital Prague Ke Karlovu 2 12808 Prague Czech Republic

International Patient Organisation for Primary Immunodeficiencies Downderry Cornwall PL11 3LY UK

Laboratory for Pediatric Immunology Department of Pediatrics Willem Alexander Children's Hospital Leiden University Medical Center Albinusdreef 2 2333 ZA Leiden The Netherlands

Newborn Screening Clinical Chemistry and Pharmacology Lab Meyer Children's University Hospital 50139 Florence Italy

Office of the International Society for Neonatal Screening Reigerskamp 273 3607 HP Maarssen The Netherlands

Regional Coordinating Center for Rare Diseases European Reference Network for Hereditary Metabolic Diseases Udine University Hospital Piazzale Santa Maria della Misericordia 15 33100 Udine Italy

Sheffield Children's NHS Foundation Trust Western Bank Sheffield S10 2TH UK

See more in PubMed

Chace D.H., Kalas T.A., Naylor E.W. Use of Tandem Mass Spectrometry for Multianalyte Screening of Dried Blood Specimens from Newborns. Clin. Chem. 2003;49:1797–1817. doi: 10.1373/clinchem.2003.022178. PubMed DOI

Hoffmann G.F., Lindner M., Loeber J.G. 50 years of newborn screening. J. Inherit. Metab. Dis. 2014;37:163–164. doi: 10.1007/s10545-014-9688-5. PubMed DOI

Groselj U., Tansek M.Z., Battelino T. Fifty years of phenylketonuria newborn screening—A great success for many, but what about the rest? Mol. Genet. Metab. 2014;113:8–10. doi: 10.1016/j.ymgme.2014.07.019. PubMed DOI

Moliner A.M., Waligora J. The European Union Policy in the Field of Rare Diseases. Rare Diseases Epidemiology: Update and Overview. In: Posada de la Paz M., Taruscio D., Groft S.C., editors. Advances in Experimental Medicine and Biology. Volume 1031. Springer Nature; Basingstoke, UK: 2017. pp. 561–587. PubMed DOI

Nguengang Wakap S., Lambert D.M., Olry A., Rodwell C., Gueydan C., Lanneau V., Murphy D., Le Cam Y., Rath A. Estimating cumulative point prevalence of rare diseases: Analysis of the Orphanet database. Eur. J. Hum. Genet. 2020;28:165–173. doi: 10.1038/s41431-019-0508-0. PubMed DOI PMC

Korver A.M.H., Smith R.J.H., Van Camp G., Schleiss M.R., Bitner-Glindzicz M.A.K., Lustig L.R., Usami S.-I., Boudewyns A.N. Congenital hearing loss. Nat. Rev. Dis. Prim. 2017;3:1–17. doi: 10.1038/nrdp.2016.94. PubMed DOI PMC

Liu Y., Chen S., Zühlke L., Black G., Choy M.-K., Li N., Keavney B.D. Global birth prevalence of congenital heart defects 1970–2017: Updated systematic review and meta-analysis of 260 studies. Int. J. Epidemiol. 2019;48:455–463. doi: 10.1093/ije/dyz009. PubMed DOI PMC

Nkhoma E.T., Poole C., Vannappagari V., Hall S.A., Beutler E. The global prevalence of glucose-6-phosphate dehydrogenase deficiency: A systematic review and meta-analysis. Blood Cells, Mol. Dis. 2009;42:267–278. doi: 10.1016/j.bcmd.2008.12.005. PubMed DOI

Scarpa M., Bonham J.R., Dionisi-Vici C., Prevot J., Pergent M., Meyts I., Mahlaoui N., Schielen P.C. Newborn screening as a fully integrated system to stimulate equity in neonatal screening in Europe. Lancet Reg. Heal. Eur. 2022;13:100311. doi: 10.1016/j.lanepe.2022.100311. PubMed DOI PMC

Jones S.A., Cheillan D., Chakrapani A., Church H.J., Heales S., Wu T.H.Y., Morton G., Roberts P., Sluys E.F., Burlina A. Application of a Novel Algorithm for Expanding Newborn Screening for Inherited Metabolic Disorders across Europe. Int. J. Neonatal Screen. 2022;8:20. doi: 10.3390/ijns8010020. PubMed DOI PMC

Loeber J., Platis D., Zetterström R., Almashanu S., Boemer F., Bonham J., Borde P., Brincat I., Cheillan D., Dekkers E., et al. Neonatal Screening in Europe Revisited: An ISNS Perspective on the Current State and Developments Since 2010. Int. J. Neonatal Screen. 2021;7:15. doi: 10.3390/ijns7010015. PubMed DOI PMC

Pollitt R.J. International perspectives on newborn screening. J. Inherit. Metab. Dis. 2006;29:390–396. doi: 10.1007/s10545-006-0259-2. PubMed DOI

Gray J.A.M., Patnick J., Blanks R.G. Maximising benefit and minimising harm of screening. BMJ. 2008;336:480–483. doi: 10.1136/bmj.39470.643218.94. PubMed DOI PMC

Andermann A., Blancquaert I., Beauchamp S., Dery V. Revisting wilson and Jungner in the genomic age: A review of screening criteria over the past 40 years. Bull. World Health Organ. 2008;86:317–319. doi: 10.2471/BLT.07.050112. PubMed DOI PMC

Wilson J.M.G., Jungner G. Principles and Practice of Screening for Disease. World Health Organization. 1968. [(accessed on 17 February 2022)]. Available online: https://apps.who.int/iris/handle/10665/37650.

Copenhagen: WHO Regional Office for Europe Increase Effectiveness, Maximize Benefits and Minimize Harm. 2020. [(accessed on 17 February 2022)]. Available online: https://apps.who.int/iris/bitstream/handle/10665/330829/9789289054782-eng.pdf.

Petros M. Revisiting the Wilson-Jungner criteria: How can supplemental criteria guide public health in the era of genetic screening? Genet. Med. 2012;14:129–134. doi: 10.1038/gim.0b013e31823331d0. PubMed DOI

Koracin V., Loeber J.G., Mlinaric M., Battelino T., Bonham J.R., Groselj U. COVID-NBS ISNS global network. Global Impact of Covid-19 on Newborn Screening Programs. BMJ Glob. Health. 2022;7:e007780. doi: 10.1136/bmjgh-2021-007780. PubMed DOI PMC

Haute Autorité de Santé: Évaluation a Priori de L’extension du Dépistage Néonatal à une ou Plusieurs Erreurs Innées du Métabolisme par la Technique de Spectrométrie de Masse en Tandem en Population Générale en France. [(accessed on 18 February 2022)]. Available online: https://www.has-sante.fr/upload/docs/application/pdf/2020-01/synthese_dnn_eim.pdf.

Lampret B.R., Remec I., Torkar A.D., Tanšek M., Šmon A., Koračin V., Čuk V., Perko D., Ulaga B., Jelovšek A.M., et al. Expanded newborn screening program in Slovenia using tandem mass spectrometry and confirmatory next generation sequencing genetic testing. Slov. J. Public Heal. 2020;59:256–263. doi: 10.2478/sjph-2020-0032. PubMed DOI PMC

Smon A., Lampret B.R., Groselj U., Tansek M.Z., Kovač J., Perko D., Bertok S., Battelino T., Podkrajsek K.T. Next generation sequencing as a follow-up test in an expanded newborn screening programme. Clin. Biochem. 2018;52:48–55. doi: 10.1016/j.clinbiochem.2017.10.016. PubMed DOI

Groselj U., Kovac J., Sustar U., Mlinaric M., Fras Z., Podkrajsek K.T., Battelino T. Universal screening for familial hypercholesterolemia in children: The Slovenian model and literature review. Atherosclerosis. 2018;277:383–391. doi: 10.1016/j.atherosclerosis.2018.06.858. PubMed DOI

Gramer G., Fang-Hoffmann J., Feyh P., Klinke G., Monostori P., Mütze U., Posset R., Weiss K.H., Hoffmann G.F., Okun J.G. Newborn Screening for Vitamin B12 Deficiency in Germany—Strategies, Results, and Public Health Implications. J. Pediatr. 2020;216:165–172. doi: 10.1016/j.jpeds.2019.07.052. PubMed DOI

Mütze U., Walter M., Keller M., Gramer G., Garbade S.F., Gleich F., Haas D., Posset R., Grünert S.C., Hennermann J.B., et al. Health Outcomes of Infants with Vitamin B12 Deficiency Identified by Newborn Screening and Early Treated. J. Pediatr. 2021;235:42–48. doi: 10.1016/j.jpeds.2021.02.009. PubMed DOI

Boy N., Mengler K., Thimm E., Schiergens K.A., Marquardt T., Weinhold N., Marquardt I., Das A.M., Freisinger P., Grünert S.C., et al. Newborn screening: A disease-changing intervention for glutaric aciduria type 1. Ann. Neurol. 2018;83:970–979. doi: 10.1002/ana.25233. PubMed DOI

Mütze U., Henze L., Gleich F., Lindner M., Grünert S.C., Spiekerkoetter U., Santer R., Blessing H., Thimm E., Ensenauer R., et al. Newborn screening and disease variants predict neurological outcome in isovaleric aciduria. J. Inherit. Metab. Dis. 2021;44:857–870. doi: 10.1002/jimd.12364. PubMed DOI

Mütze U., Garbade S.F., Gramer G., Lindner M., Freisinger P., Grünert S.C., Hennermann J., Ensenauer R., Thimm E., Zirnbauer J., et al. Long-term Outcomes of Individuals With Metabolic Diseases Identified Through Newborn Screening. Pediatrics. 2020;146:e20200444. doi: 10.1542/peds.2020-0444. PubMed DOI

Sörensen L., Von Döbeln U., Åhlman H., Ohlsson A., Engvall M., Naess K., Backman-Johansson C., Nordqvist Y., Wedell A., Zetterström R.H. Expanded Screening of One Million Swedish Babies with R4S and CLIR for Post-Analytical Evaluation of Data. Int. J. Neonatal Screen. 2020;6:42. doi: 10.3390/ijns6020042. PubMed DOI PMC

Hall K. 12th ISNS European Regional Meeting Oral and Poster Abstracts. Int. J. Neonatal Screen. 2021;7:71. doi: 10.3390/ijns7040071. PubMed DOI PMC

Groselj U., Tansek M.Z., Smon A., Angelkova N., Anton D., Baric I., Djordjevic M., Grimci L., Ivanova M., Kadam A., et al. Newborn screening in southeastern Europe. Mol. Genet. Metab. 2014;113:42–45. doi: 10.1016/j.ymgme.2014.07.020. PubMed DOI

Koracin V., Mlinaric M., Baric I., Brincat I., Djordjevic M., Torkar A.D., Fumic K., Kocova M., Milenkovic T., Moldovanu F., et al. Current Status of Newborn Screening in Southeastern Europe. Front. Pediatr. 2021;9:648939. doi: 10.3389/fped.2021.648939. PubMed DOI PMC

Call to Action—Newborn Screening for Rare Diseases. [(accessed on 18 February 2022)]. Available online: https://ipopi.org/wp-content/uploads/2020/06/Call-to-Action-NBS-Screen-4-Rare.pdf.

ERN RITA Takes an Active Role in the Launch Meeting of the ERN Expert Platform for Newborn Screening. [(accessed on 18 February 2022)]. Available online: https://ern-rita.org/ern-rita-takes-an-active-role-in-the-launch-meeting-of-the-ern-expert-platform-for-newborn-screening/

Eurordis-Rare Diseases Europe Key Principles for Newborn Screening. [(accessed on 18 February 2022)]. Available online: https://www.eurordis.org/newbornscreening.

International Survey on Phenylketonuria Newborn Screening

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