Neonatal screening (NBS) was initiated in Europe during the 1960s with the screening for phenylketonuria. The panel of screened disorders ("conditions") then gradually expanded, with a boost in the late 1990s with the introduction of tandem mass spectrometry (MS/MS), making it possible to screen for 40-50 conditions using a single blood spot. The most recent additions to screening programmes (screening for cystic fibrosis, severe combined immunodeficiency and spinal muscular atrophy) were assisted by or realised through the introduction of molecular technologies. For this survey, we collected data from 51 European countries. We report the developments between 2010 and 2020 and highlight the achievements reached with the progress made in this period. We also identify areas where further progress can be made, mainly by exchanging knowledge and learning from experiences in neighbouring countries. Between 2010 and 2020, most NBS programmes in geographical Europe matured considerably, both in terms of methodology (modernised) and with regard to the panel of conditions screened (expanded). These developments indicate that more collaboration in Europe through European organisations is gaining momentum. We can only accomplish the timely detection of newborn infants potentially suffering from one of the many rare diseases and take appropriate action by working together.

Arbes Health Care Centre Yerevan 0014 Armenia

Center for Preventive Paediatrics 3022 Limassol Cyprus

Centre for Inherited Metabolic Diseases Karolinska University Hospital and Department of Molecular Medicine and Surgery Karolinska Institute SE 17 76 Stockholm Sweden

Centre for Medical Genetics 08661 Vilnius Lithuania

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

Child and Adolescent Health Department 06430 Ankara Turkey

Children's Clinic 1083 Budapest Hungary

Children's University Hospital 1004 Riga Latvia

CHU Domaine du Sart Tilman 4000 Liège Belgium

Clinical and Diagnostic Center Pharmbiotest LLC 93000 Rubizhne Ukraine

Department Genetics and Molecular Medicine Landspitali Reykjavik 108 Iceland

Department of Newborn Screening Institute of Child Health 11527 Athens Greece

Department of Pediatrics and Adolescent Medicine 1090 Vienna Austria

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

Department of Pediatrics University Clinical Centre Tuzla 75000 Bosnia and Herzegovina

Groupement Hospitalier Est 69500 Bron France

Institute for Sick Children 81000 Podgorica Montenegro

Institute of Mother and Child 01 211 Warsaw Poland

International Society for Neonatal Screening Office 3721CK Bilthoven The Netherlands

Laboratoire National de Santé 3555 Dudelange Luxembourg

Málaga Regional University Hospital Institute of Biomedical Research IBIMA 29011 Málaga Spain

Mater Dei Hospital Tal Qroqq Msida MSD2090 Msida Malta

Medical Faculty 1000 Skopje North Macedonia

Medical Faculty University of Tartu 50411 Tart Estonia

Meyer Hospital 50139 Florence Italy

Mother and Child Health Care Institute of Serbia Belgrade 11070 Serbia

National Centre Health and Reproductive and Medical Genetics 2062 Chisinau Moldova

National Genetic Laboratory Hospital Maichin Dom 1431 Sofia Bulgaria

National Institute for Mother and Child Health 050474 Bucharest Romania

National Institute of Health 4000 055 Porto Portugal

Neonatal Screening Center 115580 Moscow Russia

Neonatal Screening Laboratory Children's Hospital CH 8032 Zürich Switzerland

NeugoGenetic and Metabolic Center Tbilisi 0194 Georgia

Newborn Blood Spot Screening Laboratory Dublin 1 Ireland

Newborn Screening Centre Banska Bystrica 97401 Slovakia

Newborn Screening Centre Turku University Hospital 20521 Turku Finland

Newborn Screening Laboratories Tel HaShomer 52621 Ramat Gan Israel

Norwegian National Unit for Newborn Screening 0424 Oslo Norway

Republican Center Mother and Child Screening Tashkent 100164 Uzbekistan

Republican Scientific Centre for Gynaecology and Perinatology Almaty 050020 Kazakhstan

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

Staten Serum Institute 2300 Copenhagen Denmark

University Children's Hospital 1000 Ljubljana Slovenia

University Clinic 04103 Leipzig Germany

University Clinical Centre Pristina 10000 Kosovo

University Hospital Medical Centre Zagreb 10000 Zagreb Croatia

Zobrazit více v PubMed

Woolf L.I., Adams J. The Early History of PKU. Int. J. Neonatal Screen. 2020;6:59. doi: 10.3390/ijns6030059. PubMed DOI PMC

Følling I.A. Über Ausscheidung von phenylbrenztraubensäure in den harn als stoffwechselanomalie in verbindung mit imbezillität. Hoppe Seyler´s Z. Physiol. Chem. 1934;227:169–181. doi: 10.1515/bchm2.1934.227.1-4.169. (In German) DOI

Centerwall W.R. Phenylketonuria. J. Am. Med. Assoc. 1957;165:392. doi: 10.1001/jama.1957.02980220076022. PubMed DOI

Laxova R. Lionel Sharples Penrose, 1898–1972: A personal memoir in celebration of the centenary of his birth. Genetics. 1998;150:1333–1340. PubMed PMC

Guthrie R., Susi A. A simple phenylalanine method for detecting phenylketonuria in large populations of newborn infants. Pediatrics. 1963;32:338–343. PubMed

Dussault J.H., Laberge C. Thyroxine (T4) determination by radioimmunological method in dried blood eluate: New diagnostic method of neonatal hypothyroidism? Union Med. Can. 1973;102:2062–2064. PubMed

Millington D.S., Kodo N., Norwood D.L., Roe C.R. Tandem mass spectrometry: A new method for acylcarnitine profiling with potential for neonatal screening for inborn errors of metabolism. J. Inherit. Metab. Dis. 1990;13:321–324. doi: 10.1007/BF01799385. PubMed DOI

Rashed M.S., Ozand P.T., Harrison M.E., Watkins P.J.F., Evans S., Baillie P.T.A. Electrospray tandem mass spectrometry in the diagnosis of organic acidemias. Rapid Commun. Mass Spectrom. 1994;8:129–133. doi: 10.1002/rcm.1290080124. DOI

Schulze A., Lindner M., Kohlmüller D., Olgemöller K., Mayatepek E., Hoffmann G.F. Expanded newborn screening for inborn errors of metabolism by electrospray ionization-tandem mass spectrometry: Results, outcome, and implications. Pediatrics. 2003;111:1399–1406. doi: 10.1542/peds.111.6.1399. PubMed DOI

Wilson J.M., Jungner Y.G. Principles and practice of mass screening for disease. Bull. WHO. 1968;65:281–393. PubMed

International Society for Neonatal Screening—Region Europe. [(accessed on 18 November 2020)]; Available online: https://www.isns-neoscreening.org/isns-regions/region-europe/

Wikipedia List of European Countries by Population. [(accessed on 27 September 2020)]; Available online: https://en.wikipedia.org/wiki/List_of_European_countries_by_population.

World Bank Data. Birth Rate. [(accessed on 27 September 2020)]; Available online: https://data.worldbank.org/indicator/sp.dyn.cbrt.in.

Burgard P., Cornel M.C., Di Filippo F., Heage G., Hoffmann G.F., Lindner M., Loeber J.G., Rigter T., Rupp K., Taruscio D., et al. Short Executive Summary of the Report on the Practices of Newborn Screening for Rare Disorders in Member States of the European Union, Candidate and Potential Candidate, and EFTA Countries. International Society for Neonatal Screening; Bilthoven, The Netherlands: 2011. [(accessed on 18 November 2020)]. Available online: http://www.isns-neoscreening.org/wp-content/uploads/2016/06/Summary20111018.pdf.

Cornel M.C., Rigter T., Weinreich S.S., Burgard P., Hoffmann G.F., Lindner M., Loeber J.G., Rupp K., Taruscio D., Vittozzi L. Newborn screening in Europe; expert opinion document. Eur. J. Hum. Genet. 2014;22:12–17. doi: 10.1038/ejhg.2013.90. PubMed DOI PMC

Loeber J.G. European union should actively stimulate and harmonise neonatal screening initiatives. Int. J. Neonatal Screen. 2018;4:32. doi: 10.3390/ijns4040032. PubMed DOI PMC

Loeber J.G. Neonatal screening in Europe; situation in 2004. J. Inherhit. Metab. Dis. 2007;30:430–438. doi: 10.1007/s10545-007-0644-5. PubMed DOI

Loeber J.G., Burgard P., Cornel M.C., Rigter T., Weinreich S.S., Rupp K., Hoffmann G.F., Vittozzi L. Newborn screening programmes in Europe; arguments and efforts regarding harmonization. Part 1—From blood spot to screening result. J. Inherit. Metab. Dis. 2012;35:603–611. doi: 10.1007/s10545-012-9483-0. PubMed DOI

Burgard P., Rupp K., Lindner M., Haege G., Rigter T., Weinreich S.S., Loeber J.G., Taruscio D., Vittozzi L., Cornel M.C., et al. Newborn screening programmes in Europe; arguments and efforts regarding harmonization. Part 2—From screening laboratory results to treatment, follow-up and quality assurance. J. Inherit. Metab. Dis. 2012;35:613–625. doi: 10.1007/s10545-012-9484-z. PubMed DOI

Therrell B.L., Padilla C.D., Loeber J.G., Kneisser I., Saadallah A., Borrajo G.J., Adams J. Current status of newborn screening worldwide: 2015. Semin. Perinatol. 2015;39:171–187. doi: 10.1053/j.semperi.2015.03.002. PubMed DOI

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

Roscher A. Unpublished work. 2021.

Estrella J., Wilcken B., Carpenter K., Bhattacharya K., Tchan M., Wiley V. Expanded newborn screening in New South Wales: Missed cases. J. Inherit. Metab. Dis. 2014;37:881–887. doi: 10.1007/s10545-014-9727-2. PubMed DOI

Boneh A., Andresen B.S., Gregersen N., Ibrahim M., Tzanakos N., Peters H., Yaplito-Lee J., Pitt J. VLCAD deficiency: Pitfalls in newborn screening and confirmation of diagnosis by mutation analysis. Mol. Genet. Metab. 2006;88:166–170. doi: 10.1016/j.ymgme.2005.12.012. PubMed DOI

Schymik I., Liebig M., Mueller M., Wendel U., Mayatepek E., Strauss A.W., Wanders R.J.A., Spiekerkoetter U. Pitfalls of neonatal screening for very-long-chain acyl-CoA dehydrogenase deficiency using tandem mass spectrometry. J. Pediatrics. 2006;149:128–130. doi: 10.1016/j.jpeds.2006.02.037. PubMed DOI

Tangeraas T., Sæves I., Klingenberg C., Jørgensen J., Kristensen E., Gunnarsdottir G., Hansen E., Strand J., Lundman E., Ferdinandusse S., et al. Performance of expanded newborn screening in Norway supported by post-analytical bioinformatics tools and rapid second-tier dna analyses. Int. J. Neonatal Screen. 2020;6:51. doi: 10.3390/ijns6030051. PubMed DOI PMC

Van Rijt W.J., Schielen P.C., Özer Y., Bijsterveld K., Van der Sluijs F.H., Derks T.G., Heiner-Fokkema M.R. Instability of acylcarnitines in stored dried blood spots: The impact on retrospective analysis of biomarkers for inborn errors of metabolism. Int. J. Neonatal Screen. 2020;6:83–95. doi: 10.3390/ijns6040083. PubMed DOI PMC

General Data Protection Regulation (GDPR) 2016. [(accessed on 18 November 2020)]; Available online: https://eur-lex.europa.eu/legal-content/EN/TXT/?uri=celex%3A32016R0679.

Lanting C.I., Van Tijn D.A., Loeber J.G., Vulsma T., de Vijlder J.J., Verkerk P.H. Clinical effectiveness and cost-effectiveness of the use of the thyroxine/thyroxine-binding globulin ratio to detect congenital hypothyroidism of thyroidal and central origin in a neonatal screening program. Pediatrics. 2005;116:168–173. doi: 10.1542/peds.2004-2162. PubMed DOI

Stroek K., Heijboer A.C., Bouva M.J., Van der Ploeg C.P.B., Heijnen M.-L.A., Weijman G., Bosch A.M., De Jonge R., Schielen P.C.J.I., Van Trotsenburg A.S.P., et al. Critical evaluation of the newborn screening for congenital hypothyroidism in the Netherlands. Eur. J. Endocrinol. 2020;183:265–273. doi: 10.1530/EJE-19-1048. PubMed DOI

Boemer F., Caberg J.-H., Dideberg V., Dardenne D., Bours V., Hiligsmann M., Dangouloff T., Servais L. Newborn screening for SMA in Southern Belgium. Neuromuscul. Disord. 2019;29:343–349. doi: 10.1016/j.nmd.2019.02.003. PubMed DOI

Vill K., Köbel H., Schwartz O., Blaschek A., Olgemöller B., Harms E., Burggraf S., Röschinger W., Dumer J., Gläser D., et al. One year of newborn screening for SMA. Results of a German pilot project. J. Neuromuscul. Dis. 2019;6:503–515. doi: 10.3233/JND-190428. PubMed DOI PMC

Burlina A.B., Polo G., Salviati L., Duro G., Zizzo C., Dardis A., Bembi B., Cazzorla C., Rubert L., Zordan R., et al. Newborn screening for lysosomal storage disorders by tandem mass spectrometry in North East Italy. J. Inherit. Metab. Dis. 2018;41:209–219. doi: 10.1007/s10545-017-0098-3. PubMed DOI

CLIR—Collaborative Laboratory Integrated Reports. [(accessed on 15 December 2020)]; Available online: https://clir.mayo.edu/

McHugh D., Cameron C.A., Abdenur J.E., Abdulrahman M., Adair O., Al Nuaimi S.A., Ahlman H., Allen J.J., Antonozzi I., Archer S., et al. Clinical validation of cutoff target ranges in newborn screening of metabolic disorders by tandem mass spec-trometry: A worldwide collaborative project. Genet. Med. 2011;13:230–254. doi: 10.1097/GIM.0b013e31820d5e67. PubMed DOI

Marquardt G., Currier R., McHugh D.M., Gavrilov D., Magera M.J., Matern D., Oglesbee D., Raymond K., Rinaldo P., Smith E.H., et al. Enhanced interpretation of newborn screening results without analyte cutoff values. Genet. Med. 2012;14:648–655. doi: 10.1038/gim.2012.2. PubMed DOI

Baerg M.M.M., Stoway S.D., Hart J., Mott L., Peck D.S., Nett S.L., Eckerman J.S., Lacey J.M., Turgeon C.T., Gavrilov D., et al. Precision newborn screening for lysosomal disorders. Genet. Med. 2018;20:847–854. doi: 10.1038/gim.2017.194. 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

Lundman E., Gaup H.J., Bakkeheim E., Olafsdottir E.J., Rootwelt T., Storrøsten O.T., Pettersen R.D. Implementation of newborn screening for cystic fibrosis in Norway. Results from the first three years. J. Cyst. Fibros. 2016;15:318–324. doi: 10.1016/j.jcf.2015.12.017. PubMed DOI

Severin F., Borry P., Cornel M.C., Daniels N., Fellmann F., Hodgson S.V., Howard H.C., John J., Kääriäinen H., Kayserili H., et al. Points to consider for prioritizing clinical genetic testing services: A European consensus process oriented at accountability for reasonableness. Eur. J. Hum. Genet. 2015;23:729–735. doi: 10.1038/ejhg.2014.190. PubMed DOI PMC

International Society for Neonatal Screening Databank Disorders. [(accessed on 15 December 2020)]; Available online: https://membership.isns-neoscreening.org/disorders/

International Society for Neonatal Screening Guidelines. [(accessed on 15 December 2020)]; Available online: https://www.isns-neoscreening.org/isns-general-guidelines-for-neonatal-screening/

International Survey on Phenylketonuria Newborn Screening

Cystathionine β-Synthase Deficiency in the E-HOD Registry-Part II: Dietary and Pharmacological Treatment

Patient preferences in genetic newborn screening for rare diseases: study protocol

Newborn Screening in a Pandemic-Lessons Learned

Towards Achieving Equity and Innovation in Newborn Screening across Europe

Impact of Newborn Screening and Early Dietary Management on Clinical Outcome of Patients with Long Chain 3-Hydroxyacyl-CoA Dehydrogenase Deficiency and Medium Chain Acyl-CoA Dehydrogenase Deficiency-A Retrospective Nationwide Study