{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T03:04:44Z","timestamp":1771470284893,"version":"3.50.1"},"reference-count":25,"publisher":"Georg Thieme Verlag KG","issue":"06","license":[{"start":{"date-parts":[[2023,9,25]],"date-time":"2023-09-25T00:00:00Z","timestamp":1695600000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Klin Padiatr"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>\n          Background  Sickle cell disease (SCD) is a group of hemoglobinopathies with\n                    a common point mutation causing the production of sickle cell hemoglobin (HbS).\n                    In high-throughput newborn screening (NBS) for SCD, a two-step procedure is\n                    suitable, in which qPCR first pre-selects relevant samples that are\n                    differentiated by a second method.<\/jats:p><jats:p>\n          Methods  Three NBS centers using qPCR-based primary screening for SCD\n                    performed a laboratory comparison. Methods using tandem MS or HPLC were used for\n                    differentiation.<\/jats:p><jats:p>\n          Results  In a benchmarking test, 450 dried blood samples were analyzed.\n                    Samples containing HbS were detected as reliably by qPCR as by methods\n                    established for hemoglobinopathy testing. In a two-step screening approach, the\n                        2nd-tier-analyses have to distinguish the carrier status from\n                    pathological variants. In nine months of regular screening, a total of 353,219\n                    samples were analyzed using two-stage NBS procedures. The 1st-tier\n                    screening by qPCR reduced the number of samples for subsequent differentiation\n                    by&gt;99.5%. Cases with carrier status or other variants were\n                    identified as inconspicuous while 78 cases with SCD were revealed. The derived\n                    incidence of 1:4,773, is in good agreement with previously published\n                    incidences.<\/jats:p><jats:p>\n          Conclusion  In high-throughput NBS for SCD, qPCR is suitable to focus\n                        2nd-tier analyses on samples containing HbS, while being\n                    unaffected by factors such as prematurity or transfusions. The substantial\n                    reduction of samples numbers positively impacts resource conservation,\n                    sustainability, and cost-effectiveness. No false negative cases came to\n                    attention.<\/jats:p>","DOI":"10.1055\/a-2153-7789","type":"journal-article","created":{"date-parts":[[2023,9,25]],"date-time":"2023-09-25T22:50:23Z","timestamp":1695682223000},"page":"366-372","source":"Crossref","is-referenced-by-count":8,"title":["High Throughput Newborn Screening for Sickle Cell Disease \u2013\n                    Application of Two-Tiered Testing with a qPCR-Based Primary\n                    screen"],"prefix":"10.1055","volume":"235","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6293-0831","authenticated-orcid":false,"given":"Joachim","family":"Janda","sequence":"first","affiliation":[{"name":"Department of General Pediatrics, Division of Neuropediatrics and\n                    Metabolic Medicine, University Hospital Heidelberg Center of Paediatric and\n                    Adolescent Medicine, Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sebastian","family":"Hegert","sequence":"first","affiliation":[{"name":"Screening-Laboratory Hannover, Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Bzdok","sequence":"additional","affiliation":[{"name":"Laboratory Becker & Colleagues, Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1636-0954","authenticated-orcid":false,"given":"Rafael","family":"Tesorero","sequence":"additional","affiliation":[{"name":"Department of General Pediatrics, Division of Neuropediatrics and\n                    Metabolic Medicine, University Hospital Heidelberg Center of Paediatric and\n                    Adolescent Medicine, Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ute","family":"Holtkamp","sequence":"additional","affiliation":[{"name":"Screening-Laboratory Hannover, Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siegfried","family":"Burggraf","sequence":"additional","affiliation":[{"name":"Laboratory Becker & Colleagues, Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elfriede","family":"Schuhmann","sequence":"additional","affiliation":[{"name":"Laboratory Becker & Colleagues, Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Friedrike","family":"H\u00f6rster","sequence":"additional","affiliation":[{"name":"Department of General Pediatrics, Division of Neuropediatrics and\n                    Metabolic Medicine, University Hospital Heidelberg Center of Paediatric and\n                    Adolescent Medicine, Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georg F.","family":"Hoffmann","sequence":"additional","affiliation":[{"name":"Department of General Pediatrics, Division of Neuropediatrics and\n                    Metabolic Medicine, University Hospital Heidelberg Center of Paediatric and\n                    Adolescent Medicine, Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2313-3311","authenticated-orcid":false,"given":"Nils","family":"Janzen","sequence":"additional","affiliation":[{"name":"Screening-Laboratory Hannover, Hannover, Germany"},{"name":"Dept. of Clinical Chemistry, Hannover Medical School, Hannover,\n                    Germany"},{"name":"Division of Laboratory Medicine, Kinderkrankenhaus auf der Bult,\n                    Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00fcrgen G","family":"Okun","sequence":"additional","affiliation":[{"name":"Department of General Pediatrics, Division of Neuropediatrics and\n                    Metabolic Medicine, University Hospital Heidelberg Center of Paediatric and\n                    Adolescent Medicine, Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc","family":"Becker","sequence":"additional","affiliation":[{"name":"Laboratory Becker & Colleagues, Munich, Germany"},{"name":"Department of Conservative Dentistry and Periodontology, Ludwig\n                    Maximilians University Munich, Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00fcrgen","family":"Durner","sequence":"additional","affiliation":[{"name":"Laboratory Becker & Colleagues, Munich, Germany"},{"name":"Department of Conservative Dentistry and Periodontology, Ludwig\n                    Maximilians University Munich, Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2023,9,25]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1186\/s13045-022-01237-z","article-title":"Advances in the diagnosis and treatment of sickle cell disease","volume":"15","author":"A M Brandow","year":"2022","journal-title":"J Hematol Oncol"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"e11778","DOI":"10.1016\/j.heliyon.2022.e11778","article-title":"Multispectral imaging for MicroChip electrophoresis enables point-of-care\n                    newborn hemoglobin variant screening","volume":"8","author":"R An","year":"2022","journal-title":"Heliyon"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"18010","DOI":"10.1038\/nrdp.2018.10","article-title":"Sickle cell disease","volume":"4","author":"G J Kato","year":"2018","journal-title":"Nat Rev Dis Primers"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1016\/S0140-6736(17)30193-9","article-title":"Sickle cell disease","volume":"390","author":"R E Ware","year":"2017","journal-title":"The Lancet"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1111\/j.1365-2141.2009.08054.x","article-title":"Significant 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Loeber","year":"2021","journal-title":"Int J Neonatal Screen"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"15","DOI":"10.3390\/ijns5010015","article-title":"Newborn Screening for Sickle Cell Disease in Europe","volume":"5","author":"Y Daniel","year":"2019","journal-title":"Int J Neonatal Screen"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1080\/10408363.2020.1781778","article-title":"Identifying and overcoming barriers to harmonize newborn screening programs\n                    through consensus strategies","volume":"58","author":"Y Gonz\u00e1lez-Irazabal","year":"2021","journal-title":"Crit Rev Clin Lab Sci"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"1653","DOI":"10.1373\/clinchem.2010.153494","article-title":"Impact of second-tier testing on the effectiveness of newborn screening","volume":"56","author":"D H Chace","year":"2010","journal-title":"Clin 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Collaborators","year":"2020","journal-title":"Lancet"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"4801087","DOI":"10.1155\/2020\/4801087","article-title":"Perceptions and Practice of Early Diagnosis of Sickle Cell Disease by Parents\n                    and Physicians in a Southwestern State of Nigeria","volume":"2020","author":"O S Olatunya","year":"2020","journal-title":"ScientificWorldJournal"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"e208","DOI":"10.1016\/S2352-3026(22)00004-7","article-title":"Estimating the risk of child mortality attributable to sickle cell anaemia in\n                    sub-Saharan Africa: a retrospective, multicentre, case-control study","volume":"9","author":"B Ranque","year":"2022","journal-title":"Lancet Haematol"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.3390\/mi12050519","article-title":"Techniques for the Detection of Sickle Cell Disease: A Review","volume":"12","author":"W A Arishi","year":"2021","journal-title":"Micromachines (Basel)"}],"container-title":["Klinische P\u00e4diatrie"],"original-title":[],"language":"de","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-2153-7789.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,10]],"date-time":"2023-11-10T00:02:59Z","timestamp":1699574579000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-2153-7789"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,25]]},"references-count":25,"journal-issue":{"issue":"06","published-online":{"date-parts":[[2023,11,9]]},"published-print":{"date-parts":[[2023,11]]}},"URL":"https:\/\/doi.org\/10.1055\/a-2153-7789","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0300-8630","1439-3824"],"issn-type":[{"value":"0300-8630","type":"print"},{"value":"1439-3824","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,25]]}}}