{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T08:03:52Z","timestamp":1784534632100,"version":"3.55.0"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,7,5]],"date-time":"2026-07-05T00:00:00Z","timestamp":1783209600000},"content-version":"vor","delay-in-days":185,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Football League\u2019s Play Smart Play Safe Programme"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Youth sports-related concussion (SRC) is a major health concern. Approximately 67% of Canadian youth participate in sports and recreation, and 93% of head injuries experienced in sports and recreation are concussions. SRCs are challenging to diagnose because symptoms are often subtle, which can affect the reliability of clinical diagnostic methods that are often subjective. As undiagnosed concussions can potentially lead to unfavourable neurological implications, objective diagnostic tools have the potential to improve diagnosis and inform prognosis. Recent research has highlighted the potential utility of plasma neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) for SRC diagnosis, offering a quantitative and cost-effective diagnostic method. However, a major gap in the literature is understanding whether the magnitude of change in NfL and GFAP levels post-SRC exceeds normal variation observed at the population level. This study evaluates NfL and GFAP as diagnostic SRC biomarkers by comparing preseason and post-SRC levels measured up to 28 days after injury to population-based reference intervals. Preseason (uninjured) and post-SRC plasma samples from the Surveillance in High Schools and Community Sports to Reduce Concussions and their Consequences study were quantified with Quanterix\u2019s Neurology-4-plex-B assay and compared to previously generated age-matched reference interval. A total of 658 preseason specimens (440 male [67%]; median [range] age, 15.9 [10.4\u201318.4] years) and 134 post-SRC specimens (72 male [54%]; median [range] age, 16.1 [11.2\u201318.4] years) were assessed. Median biomarker levels were higher at post-SRC than preseason for both NfL (preseason\/post-SRC = 5.1\/5.5\u2005pg\/ml, P = 0.0339) and GFAP (preseason\/post-SRC=51.7\/59.7\u2005pg\/ml, P &amp;lt; 0.0001). However, when compared to population controls across the same age range, 580 (88%) preseason and 119 (89%) of post-SRC measures fell within the reference interval (5th\u201395th percentile) for NfL and 644 (98%) preseason and 132 (99%) of post-SRC measures fell within the reference interval for GFAP. Further, the number of participants within or above the reference interval (&amp;gt;95th percentile) did not differ between preseason and post-SRC groups for either NfL (P &amp;gt; 0.9999) or GFAP (P &amp;gt; 0.9999). Body mass index was inversely associated with the distribution of NfL (5th\u201350th\/50th\u201395th = 23.02\/22.15, P = 0.0083; 5th\u201350th\/50th\u201395th = 24.37\/21.74, P = 0.0038) and GFAP (5th\u201350th\/50th\u201395th = 23.12\/22.29, P = 0.0219; 5th\u201350th\/50th\u201395th = 25.03\/22.27, P = 0.0025) within the reference interval, which may explain the skew of NfL and GFAP levels in the SHRed participants compared to population controls at both preseason and post-SRC. We conclude that plasma NfL and GFAP measured up to 28 days post-SRC do not meet criteria for clinical significance as stand-alone post-acute diagnostic biomarkers for adolescent SRC.<\/jats:p>","DOI":"10.1093\/braincomms\/fcag250","type":"journal-article","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T13:19:48Z","timestamp":1783084788000},"source":"Crossref","is-referenced-by-count":0,"title":["Using reference intervals to improve interpretation of youth sport-related concussion biomarkers using a research platform"],"prefix":"10.1093","volume":"8","author":[{"given":"Kidus","family":"Achalu","sequence":"first","affiliation":[{"name":"Djavad Mowafaghian Centre for Brain Health, University of British Columbia , Vancouver, British Columbia V6T 1Z3 ,","place":["Canada"]},{"name":"Department of Pathology and Laboratory Medicine, University of British Columbia , Vancouver, British Columbia V6T 1Z3 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer G","family":"Cooper","sequence":"additional","affiliation":[{"name":"Djavad Mowafaghian Centre for Brain Health, University of British Columbia , Vancouver, British Columbia V6T 1Z3 ,","place":["Canada"]},{"name":"Department of Pathology and Laboratory Medicine, University of British Columbia , Vancouver, British Columbia V6T 1Z3 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason B","family":"Tabor","sequence":"additional","affiliation":[{"name":"Faculty of Kinesiology, Sport Injury Prevention Research Centre, University of Calgary , Calgary, Alberta T2N 1N4 ,","place":["Canada"]},{"name":"Hotchkiss Brain Institute, University of Calgary , Calgary, Alberta T2N 1N4 ,","place":["Canada"]},{"name":"Alberta Children\u2019s Hospital Research Institute, University of Calgary , Calgary, Alberta T2N 1N4 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Ghodsi","sequence":"additional","affiliation":[{"name":"Djavad Mowafaghian Centre for Brain Health, University of British Columbia , Vancouver, British Columbia V6T 1Z3 ,","place":["Canada"]},{"name":"Department of Pathology and Laboratory Medicine, University of British Columbia , Vancouver, British Columbia V6T 1Z3 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johnny","family":"Huang","sequence":"additional","affiliation":[{"name":"Djavad Mowafaghian Centre for Brain Health, University of British Columbia , Vancouver, British Columbia V6T 1Z3 ,","place":["Canada"]},{"name":"Department of Pathology and Laboratory Medicine, University of British Columbia , Vancouver, British Columbia V6T 1Z3 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nik","family":"Josafatow-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Faculty of Kinesiology, Sport Injury Prevention Research Centre, University of Calgary , Calgary, Alberta T2N 1N4 ,","place":["Canada"]},{"name":"Hotchkiss Brain Institute, University of Calgary , Calgary, Alberta T2N 1N4 ,","place":["Canada"]},{"name":"Alberta Children\u2019s Hospital Research Institute, University of Calgary , Calgary, Alberta T2N 1N4 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linden C","family":"Penner","sequence":"additional","affiliation":[{"name":"Faculty of Kinesiology, Sport Injury Prevention Research Centre, University of Calgary , Calgary, Alberta T2N 1N4 ,","place":["Canada"]},{"name":"Hotchkiss Brain Institute, University of Calgary , Calgary, Alberta T2N 1N4 ,","place":["Canada"]},{"name":"Alberta Children\u2019s Hospital Research Institute, University of Calgary , Calgary, Alberta T2N 1N4 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Stukas","sequence":"additional","affiliation":[{"name":"Djavad Mowafaghian Centre for Brain Health, University of British Columbia , Vancouver, British Columbia V6T 1Z3 ,","place":["Canada"]},{"name":"Department of Pathology and Laboratory Medicine, University of British Columbia , Vancouver, British Columbia V6T 1Z3 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3784-8753","authenticated-orcid":false,"given":"Jean-Michel","family":"Galarneau","sequence":"additional","affiliation":[{"name":"Faculty of Kinesiology, Sport Injury Prevention Research Centre, University of Calgary , Calgary, Alberta T2N 1N4 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas D","family":"Fraser","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Clinical Neurological Sciences, Western University , London, Ontario N6A 3K7 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Smirl","sequence":"additional","affiliation":[{"name":"Faculty of Kinesiology, Sport Injury Prevention Research Centre, University of Calgary , Calgary, Alberta T2N 1N4 ,","place":["Canada"]},{"name":"Hotchkiss Brain Institute, University of Calgary , Calgary, Alberta T2N 1N4 ,","place":["Canada"]},{"name":"Alberta Children\u2019s Hospital Research Institute, University of Calgary , Calgary, Alberta T2N 1N4 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7680-2892","authenticated-orcid":false,"given":"Keith O","family":"Yeates","sequence":"additional","affiliation":[{"name":"Hotchkiss Brain Institute, University of Calgary , Calgary, Alberta T2N 1N4 ,","place":["Canada"]},{"name":"Alberta Children\u2019s Hospital Research Institute, University of Calgary , Calgary, Alberta T2N 1N4 ,","place":["Canada"]},{"name":"Department of Psychology, University of Calgary , Calgary, Alberta T2N 1N4 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chantel T","family":"Debert","sequence":"additional","affiliation":[{"name":"Faculty of Kinesiology, Sport Injury Prevention Research Centre, University of Calgary , Calgary, Alberta T2N 1N4 ,","place":["Canada"]},{"name":"Hotchkiss Brain Institute, University of Calgary , Calgary, Alberta T2N 1N4 ,","place":["Canada"]},{"name":"Alberta Children\u2019s Hospital Research Institute, University of Calgary , Calgary, Alberta T2N 1N4 ,","place":["Canada"]},{"name":"Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary , Calgary, Alberta T2N 1N4 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn A","family":"Emery","sequence":"additional","affiliation":[{"name":"Faculty of Kinesiology, Sport Injury Prevention Research Centre, University of Calgary , Calgary, Alberta T2N 1N4 ,","place":["Canada"]},{"name":"Hotchkiss Brain Institute, University of Calgary , Calgary, Alberta T2N 1N4 ,","place":["Canada"]},{"name":"Alberta Children\u2019s Hospital Research Institute, University of Calgary , Calgary, Alberta T2N 1N4 ,","place":["Canada"]},{"name":"Departments of Pediatrics and Community Health Sciences, Cumming School of Medicine, University of Calgary , Calgary, Alberta T2N 1N4 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheryl L","family":"Wellington","sequence":"additional","affiliation":[{"name":"Djavad Mowafaghian Centre for Brain Health, University of British Columbia , Vancouver, British Columbia V6T 1Z3 ,","place":["Canada"]},{"name":"Department of Pathology and Laboratory Medicine, University of British Columbia , Vancouver, British Columbia V6T 1Z3 ,","place":["Canada"]},{"name":"School of Biomedical Engineering, University of British Columbia , Vancouver, British Columbia V6T 1Z3 ,","place":["Canada"]},{"name":"International Collaboration on Repair Discoveries, University of British Columbia , Vancouver, British Columbia V6T 1Z3 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,7,5]]},"reference":[{"issue":"11","key":"2026072003213056100_fcag250-B1","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1136\/bjsports-2023-106898","article-title":"Consensus statement on concussion in sport: The 6th international conference on concussion in sport\u2013Amsterdam, October 2022","volume":"57","author":"Patricios","year":"2023","journal-title":"Br J Sports 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