{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:17:47Z","timestamp":1787019467233,"version":"build-2736575974"},"reference-count":45,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2021,8,9]],"date-time":"2021-08-09T00:00:00Z","timestamp":1628467200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,8,9]],"date-time":"2021-08-09T00:00:00Z","timestamp":1628467200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","award":["543002002"],"award-info":[{"award-number":["543002002"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Clin Immunol"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Newborn screening (NBS) for severe combined immunodeficiency (SCID) is based on the detection of T-cell receptor excision circles (TRECs). TRECs are a sensitive biomarker for T-cell lymphopenia, but not specific for SCID. This creates a palette of secondary findings associated with low T-cells that require follow-up and treatment or are non-actionable. The high rate of (non-actionable) secondary findings and false-positive referrals raises questions about the harm-benefit-ratio of SCID screening, as referrals are associated with high emotional impact and anxiety for parents.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      An alternative quantitative TREC PCR with different primers was performed on NBS cards of referred newborns (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u200956) and epigenetic immune cell counting was used as for relative quantification of CD3\u2009+\u2009T-cells (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u200959). Retrospective data was used to determine the reduction in referrals with a lower TREC cutoff value or an adjusted screening algorithm.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>When analyzed with a second PCR with different primers, 45% of the referrals (25\/56) had TREC levels above cutoff, including four false-positive cases in which two SNPs were identified. With epigenetic qPCR, 41% (24\/59) of the referrals were within the range of the relative CD3\u2009+\u2009T-cell counts of the healthy controls. Lowering the TREC cutoff value or adjusting the screening algorithm led to lower referral rates but did not prevent all false-positive referrals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Second tier tests and adjustments of cutoff values or screening algorithms all have the potential to reduce the number of non-actionable secondary findings in NBS for SCID, although second tier tests are more effective in preventing false-positive referrals.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s10875-021-01107-2","type":"journal-article","created":{"date-parts":[[2021,8,9]],"date-time":"2021-08-09T04:03:21Z","timestamp":1628481801000},"page":"1762-1773","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Second Tier Testing to Reduce the Number of Non-actionable Secondary Findings and False-Positive Referrals in Newborn Screening for Severe Combined Immunodeficiency"],"prefix":"10.1007","volume":"41","author":[{"given":"Maartje","family":"Blom","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid","family":"Pico-Knijnenburg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Imholz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lotte","family":"Vissers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janika","family":"Schulze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeannette","family":"Werner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robbert","family":"Bredius","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirjam","family":"van der Burg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,8,9]]},"reference":[{"issue":"1","key":"1107_CR1","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1007\/s10875-020-00758-x","volume":"40","author":"A Bousfiha","year":"2020","unstructured":"Bousfiha A, et al. Human inborn errors of immunity: 2019 update of the IUIS Phenotypical Classification. J Clin Immunol. 2020;40(1):66\u201381.","journal-title":"J Clin Immunol"},{"key":"1107_CR2","doi-asserted-by":"publisher","first-page":"15061","DOI":"10.1038\/nrdp.2015.61","volume":"1","author":"A Fischer","year":"2015","unstructured":"Fischer A, et al. Severe combined immunodeficiencies and related disorders. Nat Rev Dis Primers. 2015;1:15061.","journal-title":"Nat Rev Dis Primers"},{"issue":"25","key":"1107_CR3","doi-asserted-by":"publisher","first-page":"2718","DOI":"10.1182\/blood-2017-05-781849","volume":"130","author":"J Heimall","year":"2017","unstructured":"Heimall J, et al. Immune reconstitution and survival of 100 SCID patients post-hematopoietic cell transplant: a PIDTC natural history study. Blood. 2017;130(25):2718\u201327.","journal-title":"Blood"},{"issue":"5","key":"1107_CR4","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1056\/NEJMoa1401177","volume":"371","author":"SY Pai","year":"2014","unstructured":"Pai SY, et al. Transplantation outcomes for severe combined immunodeficiency, 2000\u20132009. N Engl J Med. 2014;371(5):434\u201346.","journal-title":"N Engl J Med"},{"issue":"2","key":"1107_CR5","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1016\/j.jaci.2020.10.020","volume":"147","author":"R Currier","year":"2021","unstructured":"Currier R, Puck JM. SCID newborn screening: what we\u2019ve learned. J Allergy Clin Immunol. 2021;147(2):417\u201326.","journal-title":"J Allergy Clin Immunol"},{"issue":"2","key":"1107_CR6","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1016\/j.jaci.2004.10.012","volume":"115","author":"K Chan","year":"2005","unstructured":"Chan K, Puck JM. Development of population-based newborn screening for severe combined immunodeficiency. J Allergy Clin Immunol. 2005;115(2):391\u20138.","journal-title":"J Allergy Clin Immunol"},{"issue":"7","key":"1107_CR7","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1001\/jama.2014.9132","volume":"312","author":"A Kwan","year":"2014","unstructured":"Kwan A, et al. Newborn screening for severe combined immunodeficiency in 11 screening programs in the United States. JAMA. 2014;312(7):729\u201338.","journal-title":"JAMA"},{"issue":"3","key":"1107_CR8","doi-asserted-by":"publisher","first-page":"16","DOI":"10.3390\/ijns3030016","volume":"3","author":"Y-H Chien","year":"2017","unstructured":"Chien Y-H, et al. Newborn screening for severe combined immunodeficiency in Taiwan. Int J Neonatal Screen. 2017;3(3):16.","journal-title":"Int J Neonatal Screen"},{"key":"1107_CR9","doi-asserted-by":"publisher","first-page":"373","DOI":"10.3389\/fped.2019.00373","volume":"7","author":"M van der Burg","year":"2019","unstructured":"van der Burg M, et al. Universal newborn screening for severe combined immunodeficiency (SCID). Front Pediatr. 2019;7:373.","journal-title":"Front Pediatr"},{"key":"1107_CR10","doi-asserted-by":"publisher","first-page":"1948","DOI":"10.3389\/fimmu.2020.01948","volume":"11","author":"M Gi\u017cewska","year":"2020","unstructured":"Gi\u017cewska M, et al. Newborn screening for SCID and other severe primary immunodeficiency in the Polish-German transborder area: experience from the first 14 months of collaboration. Front Immunol. 2020;11:1948.","journal-title":"Front Immunol"},{"key":"1107_CR11","doi-asserted-by":"publisher","first-page":"2406","DOI":"10.3389\/fimmu.2019.02406","volume":"10","author":"A Argudo-Ram\u00edrez","year":"2019","unstructured":"Argudo-Ram\u00edrez A, et al. First universal newborn screening program for severe combined immunodeficiency in Europe. Two-years\u2019 experience in Catalonia (Spain). Front Immunol. 2019;10:2406\u20132406.","journal-title":"Front Immunol"},{"issue":"11","key":"1107_CR12","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1007\/s001090100271","volume":"79","author":"MD Hazenberg","year":"2001","unstructured":"Hazenberg MD, et al. T cell receptor excision circles as markers for recent thymic emigrants: basic aspects, technical approach, and guidelines for interpretation. J Mol Med (Berl). 2001;79(11):631\u201340.","journal-title":"J Mol Med (Berl)"},{"issue":"2","key":"1107_CR13","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1007\/s10875-020-00931-2","volume":"41","author":"D Buchbinder","year":"2021","unstructured":"Buchbinder D, et al. When screening for severe combined immunodeficiency (SCID) with T cell receptor excision circles is not SCID: a case-based review. J Clin Immunol. 2021;41(2):294\u2013302.","journal-title":"J Clin Immunol"},{"key":"1107_CR14","doi-asserted-by":"crossref","unstructured":"Amatuni GS, et al. Newborn screening for severe combined immunodeficiency and T-cell lymphopenia in California, 2010\u20132017. Pediatrics. 2019;143(2):e20182300.","DOI":"10.1542\/peds.2018-2300"},{"issue":"5","key":"1107_CR15","doi-asserted-by":"publisher","first-page":"1457","DOI":"10.1016\/j.jaip.2017.02.009","volume":"5","author":"AA Mauracher","year":"2017","unstructured":"Mauracher AA, et al. Causes of low neonatal T-cell receptor excision circles: a systematic review. J Allergy Clin Immunol Pract. 2017;5(5):1457-1460.e22.","journal-title":"J Allergy Clin Immunol Pract"},{"key":"1107_CR16","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.clim.2019.03.012","volume":"202","author":"C Thomas","year":"2019","unstructured":"Thomas C, et al. Clinical and economic aspects of newborn screening for severe combined immunodeficiency: DEPISTREC study results. Clin Immunol. 2019;202:33\u20139.","journal-title":"Clin Immunol"},{"issue":"1","key":"1107_CR17","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1007\/s10875-020-00886-4","volume":"41","author":"M Blom","year":"2021","unstructured":"Blom M, et al. Parents\u2019 perspectives and societal acceptance of implementation of newborn screening for SCID in the Netherlands. J Clin Immunol. 2021;41(1):99\u2013108.","journal-title":"J Clin Immunol"},{"issue":"1","key":"1107_CR18","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1007\/s10875-016-0347-5","volume":"37","author":"M Barbaro","year":"2017","unstructured":"Barbaro M, et al. Newborn screening for severe primary immunodeficiency diseases in Sweden-a 2-year pilot TREC and KREC screening study. J Clin Immunol. 2017;37(1):51\u201360.","journal-title":"J Clin Immunol"},{"issue":"2","key":"1107_CR19","doi-asserted-by":"publisher","first-page":"15","DOI":"10.3390\/ijns3020015","volume":"3","author":"M Dorsey","year":"2017","unstructured":"Dorsey M, Puck J. Newborn screening for severe combined immunodeficiency in the US: current status and approach to management. Int J Neonatal Screen. 2017;3(2):15.","journal-title":"Int J Neonatal Screen"},{"issue":"3","key":"1107_CR20","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1016\/j.jaci.2017.01.005","volume":"139","author":"MJ Dorsey","year":"2017","unstructured":"Dorsey MJ, et al. Treatment of infants identified as having severe combined immunodeficiency by means of newborn screening. J Allergy Clin Immunol. 2017;139(3):733\u201342.","journal-title":"J Allergy Clin Immunol"},{"issue":"1","key":"1107_CR21","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1111\/imr.12729","volume":"287","author":"JM Puck","year":"2019","unstructured":"Puck JM. Newborn screening for severe combined immunodeficiency and T-cell lymphopenia. Immunol Rev. 2019;287(1):241\u201352.","journal-title":"Immunol Rev"},{"issue":"8","key":"1107_CR22","doi-asserted-by":"publisher","first-page":"767","DOI":"10.1001\/archpedi.161.8.767","volume":"161","author":"BA Tarini","year":"2007","unstructured":"Tarini BA. The current revolution in newborn screening: new technology, old controversies. Arch Pediatr Adolesc Med. 2007;161(8):767\u201372.","journal-title":"Arch Pediatr Adolesc Med"},{"issue":"5","key":"1107_CR23","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1007\/s10545-006-0381-1","volume":"29","author":"J Hewlett","year":"2006","unstructured":"Hewlett J, Waisbren SE. A review of the psychosocial effects of false-positive results on parents and current communication practices in newborn screening. J Inherit Metab Dis. 2006;29(5):677\u201382.","journal-title":"J Inherit Metab Dis"},{"issue":"7","key":"1107_CR24","doi-asserted-by":"publisher","first-page":"778","DOI":"10.1007\/s10875-018-0550-7","volume":"38","author":"MAP Audrain","year":"2018","unstructured":"Audrain MAP, et al. Newborn screening for severe combined immunodeficiency: analytic and clinical performance of the T cell receptor excision circle assay in France (DEPISTREC Study). J Clin Immunol. 2018;38(7):778\u201386.","journal-title":"J Clin Immunol"},{"issue":"2","key":"1107_CR25","doi-asserted-by":"publisher","first-page":"11","DOI":"10.3390\/ijns3020011","volume":"3","author":"RH Zetterstr\u00f6m","year":"2017","unstructured":"Zetterstr\u00f6m RH, et al. Newborn screening for primary immune deficiencies with a TREC\/KREC\/ACTB triplex assay\u2014a three-year pilot study in Sweden. Int J Neonatal Screen. 2017;3(2):11.","journal-title":"Int J Neonatal Screen"},{"issue":"1","key":"1107_CR26","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1590\/1984-0462\/;2017;35;1;00013","volume":"35","author":"MPP Kanegae","year":"2017","unstructured":"Kanegae MPP, et al. Newborn screening for severe combined immunodeficiencies using TRECS and KRECS: second pilot study in BRAZIL. Rev Paul Pediatr. 2017;35(1):25\u201332.","journal-title":"Rev Paul Pediatr"},{"key":"1107_CR27","doi-asserted-by":"publisher","first-page":"1448","DOI":"10.3389\/fimmu.2017.01448","volume":"8","author":"E Rechavi","year":"2017","unstructured":"Rechavi E, et al. First year of Israeli newborn screening for severe combined immunodeficiency-clinical achievements and insights. Front Immunol. 2017;8:1448.","journal-title":"Front Immunol"},{"key":"1107_CR28","doi-asserted-by":"crossref","first-page":"w20254","DOI":"10.4414\/smw.2020.20254","volume":"150","author":"J Tr\u00fcck","year":"2020","unstructured":"Tr\u00fcck J, et al. Swiss newborn screening for severe T and B cell deficiency with a combined TREC\/KREC assay-management recommendations. Swiss Med Wkly. 2020;150:w20254.","journal-title":"Swiss Med Wkly"},{"issue":"5","key":"1107_CR29","doi-asserted-by":"publisher","first-page":"2060","DOI":"10.1016\/j.jaip.2021.02.006","volume":"9","author":"JE Hale","year":"2021","unstructured":"Hale JE, et al. Ten years of newborn screening for severe combined immunodeficiency (SCID) in Massachusetts. J Allergy Clin Immunol Pract. 2021;9(5):2060\u20132067.e2.","journal-title":"J Allergy Clin Immunol Pract"},{"issue":"6","key":"1107_CR30","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1007\/s11882-018-0783-9","volume":"18","author":"J Routes","year":"2018","unstructured":"Routes J, Verbsky J. Newborn screening for severe combined immunodeficiency. Curr Allergy Asthma Rep. 2018;18(6):34.","journal-title":"Curr Allergy Asthma Rep"},{"key":"1107_CR31","doi-asserted-by":"publisher","first-page":"1417","DOI":"10.3389\/fimmu.2020.01417","volume":"11","author":"J Strand","year":"2020","unstructured":"Strand J, et al. Second-tier next generation sequencing integrated in nationwide newborn screening provides rapid molecular diagnostics of severe combined immunodeficiency. Front Immunol. 2020;11:1417.","journal-title":"Front Immunol"},{"key":"1107_CR32","doi-asserted-by":"publisher","first-page":"782","DOI":"10.3389\/fimmu.2018.00782","volume":"9","author":"H Al-Mousa","year":"2018","unstructured":"Al-Mousa H, et al. High incidence of severe combined immunodeficiency disease in Saudi Arabia detected through combined T cell receptor excision circle and next generation sequencing of newborn dried blood spots. Front Immunol. 2018;9:782.","journal-title":"Front Immunol"},{"issue":"3","key":"1107_CR33","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1007\/s10875-014-0006-7","volume":"34","author":"BH Vogel","year":"2014","unstructured":"Vogel BH, et al. Newborn screening for SCID in New York State: experience from the first two years. J Clin Immunol. 2014;34(3):289\u2013303.","journal-title":"J Clin Immunol"},{"key":"1107_CR34","doi-asserted-by":"crossref","unstructured":"Baron U, et al. Epigenetic immune cell counting in human blood samples for immunodiagnostics. Sci Transl Med.\u00a02018;10(452):eaan3508.","DOI":"10.1126\/scitranslmed.aan3508"},{"key":"1107_CR35","doi-asserted-by":"publisher","first-page":"371","DOI":"10.3389\/fimmu.2020.00371","volume":"11","author":"T Kalina","year":"2020","unstructured":"Kalina T, et al. EuroFlow standardized approach to diagnostic immunophenotyping of severe PID in newborns and young children. Front Immunol. 2020;11:371.","journal-title":"Front Immunol"},{"key":"1107_CR36","unstructured":"Wilson, J.M. and Y.G. Jungner. Principles and practice of screening for disease. World Health Organization 1968.\u00a0https:\/\/apps.who.int\/iris\/handle\/10665\/37650."},{"issue":"2","key":"1107_CR37","doi-asserted-by":"publisher","first-page":"13","DOI":"10.3390\/ijns3020013","volume":"3","author":"E Rechavi","year":"2017","unstructured":"Rechavi E, et al. Newborn screening for severe combined immunodeficiency in Israel. Int J Neonatal Screen. 2017;3(2):13.","journal-title":"Int J Neonatal Screen"},{"issue":"4","key":"1107_CR38","doi-asserted-by":"publisher","first-page":"e36235","DOI":"10.1371\/journal.pone.0036235","volume":"7","author":"W-J Tu","year":"2012","unstructured":"Tu W-J, et al. Psychological effects of false-positive results in expanded newborn screening in China. PLoS ONE. 2012;7(4):e36235\u2013e36235.","journal-title":"PLoS ONE"},{"issue":"6","key":"1107_CR39","doi-asserted-by":"publisher","first-page":"1915","DOI":"10.1542\/peds.2005-2294","volume":"117","author":"EA Gurian","year":"2006","unstructured":"Gurian EA, et al. Expanded newborn screening for biochemical disorders: the effect of a false-positive result. Pediatrics. 2006;117(6):1915\u201321.","journal-title":"Pediatrics"},{"issue":"2","key":"1107_CR40","doi-asserted-by":"publisher","first-page":"e20162252","DOI":"10.1542\/peds.2016-2252","volume":"139","author":"JS Berg","year":"2017","unstructured":"Berg JS, et al. Newborn sequencing in genomic medicine and public health. Pediatrics. 2017;139(2):e20162252.","journal-title":"Pediatrics"},{"issue":"1","key":"1107_CR41","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1007\/s10875-017-0455-x","volume":"38","author":"JR King","year":"2018","unstructured":"King JR, Hammarstr\u00f6m L. Newborn screening for primary immunodeficiency diseases: history, current and future practice. J Clin Immunol. 2018;38(1):56\u201366.","journal-title":"J Clin Immunol"},{"issue":"1","key":"1107_CR42","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1186\/s12920-017-0247-4","volume":"10","author":"JM Friedman","year":"2017","unstructured":"Friedman JM, et al. Genomic newborn screening: public health policy considerations and recommendations. BMC Med Genomics. 2017;10(1):9.","journal-title":"BMC Med Genomics"},{"key":"1107_CR43","unstructured":"Reference SNP (rs) Report rs377686467. 2020 April 21, 2020 [cited 2021 16 April]; Available from: https:\/\/www.ncbi.nlm.nih.gov\/snp\/rs377686467."},{"key":"1107_CR44","unstructured":"Reference SNP (rs) Report rs1466932014. 2020 April 21, 2020 [cited 2021\u00a016 April]; Available from: https:\/\/www.ncbi.nlm.nih.gov\/snp\/rs1466932014."},{"issue":"1","key":"1107_CR45","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1186\/1471-2105-15-293","volume":"15","author":"P Bardou","year":"2014","unstructured":"Bardou P, et al. jvenn: an interactive Venn diagram viewer. BMC Bioinformatics. 2014;15(1):293.","journal-title":"BMC Bioinformatics"}],"container-title":["Journal of Clinical Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10875-021-01107-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10875-021-01107-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10875-021-01107-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,6]],"date-time":"2023-01-06T18:16:54Z","timestamp":1673029014000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10875-021-01107-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,9]]},"references-count":45,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2021,11]]}},"alternative-id":["1107"],"URL":"https:\/\/doi.org\/10.1007\/s10875-021-01107-2","relation":{},"ISSN":["0271-9142","1573-2592"],"issn-type":[{"value":"0271-9142","type":"print"},{"value":"1573-2592","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,9]]},"assertion":[{"value":"22 April 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 July 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 August 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Medical Ethics Committee of the Erasmus MC, University Medical Center, Rotterdam (MEC-2017\u20131146).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics Approval"}},{"value":"In order to participate in the SONNET study, parents have to express verbal consent when the heel prick is performed (opt-out consent).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to Participate"}},{"value":"The consent to participate was included for publication of the data.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for Publication"}},{"value":"JS and JW are employees of the company Epimune GmbH. The other authors declare no competing interests.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}]}}