{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T04:07:45Z","timestamp":1788840465204,"version":"build-2803163510"},"reference-count":41,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100006447","name":"Universit\u00e4t Z\u00fcrich","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006447","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["320030_205097"],"award-info":[{"award-number":["320030_205097"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Allergy Immunology"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Newborn screening (NBS) quantifying T\u2010cell receptor excision circles with or without kappa\u2010deleting recombination excision circles (TREC, KREC) enables early detection of severe T\u2010 and\/or B\u2010cell lymphopenia. However, both markers have limited specificity, often resulting in unnecessary referrals. We compared the effects of alternative risk\u2010stratification strategies to reduce referrals while avoiding missed cases and unnecessary delays.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We modeled the effects of multiple TREC and KREC\u2010based NBS algorithms using a comprehensive real\u2010life dataset from the first 6\u2009years of the Swiss NBS program. Stratification approaches included adjustment of cut\u2010offs and integration of clinical data such as gestational age (GA), postmenstrual age (PMA), inpatient vs. outpatient status, family history, and maternal immunosuppression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Lowering cut\u2010offs alone reduced abnormal results by 42% for TREC and 64% for KREC. The most efficient TREC algorithm, based on exact TREC levels and post\u2010menstrual age in preterm infants, reduced referrals by 61% (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u2009.0001) but missed nearly half of non\u2010SCID T\u2010cell lymphopenias and delayed referral in 2\/3 of outpatients who eventually required immunological evaluation. Integration of family history and clinical signs mitigated delays in some cases. For KREC, combining information on gestational age, maternal immunosuppression, and inpatient status enabled a &gt;10\u2010fold reduction in referrals (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u2009.0001) while still identifying all confirmed agammaglobulinemia cases except two with \u03bb5 deficiency.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Risk\u2010stratified, multistep NBS algorithms incorporating readily available clinical data can substantially reduce unnecessary referrals while preserving detection of target conditions. For KREC, simple algorithmic adjustments allow marked improvement in specificity with minimal diagnostic loss.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/pai.70412","type":"journal-article","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T15:43:40Z","timestamp":1783525420000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Optimizing\n                    <scp>TREC<\/scp>\n                    \u2010 and\n                    <scp>KREC<\/scp>\n                    \u2010based newborn screening: Risk\u2010stratified algorithms significantly reduce referrals"],"prefix":"10.1111","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2237-5327","authenticated-orcid":false,"given":"Maarja","family":"Soomann","sequence":"first","affiliation":[{"name":"Division of Immunology and The Children's Research Center University Children's Hospital Zurich, University of Zurich  Zurich 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