The Use of Biofluid Markers to Evaluate the Consequences of Sport-Related Subconcussive Head Impact Exposure: A Scoping Review

Liivia Mari Lember, Michail Ntikas, Stefania Mondello, Lindsay Wilson, Thomas G. Di Virgilio, Angus M. Hunter, Firas Kobeissy, Yehia Mechref, David I. Donaldson, Magdalena Ietswaart

Research output: Contribution to journalReview articlepeer-review


Background: Amidst growing concern about the safety of sport-related repetitive subconcussive head impacts (RSHI), biofluid markers may provide sensitive, informative, and practical assessment of the effects of RSHI exposure. Objective: This scoping review aimed to systematically examine the extent, nature, and quality of available evidence from studies investigating the effects of RSHI on biofluid markers, to identify gaps and to formulate guidelines to inform future research. Methods: PRISMA extension for Scoping Reviews guidelines were adhered to. The protocol was pre-registered through publication. MEDLINE, Scopus, SPORTDiscus, CINAHL, PsycINFO, Cochrane Library, OpenGrey, and two clinical trial registries were searched (until March 30, 2022) using descriptors for subconcussive head impacts, biomarkers, and contact sports. Included studies were assessed for risk of bias and quality. Results: Seventy-nine research publications were included in the review. Forty-nine studies assessed the acute effects, 23 semi-acute and 26 long-term effects of RSHI exposure. The most studied sports were American football, boxing, and soccer, and the most investigated markers were (in descending order): S100 calcium-binding protein beta (S100B), tau, neurofilament light (NfL), glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE), brain-derived neurotrophic factor (BDNF), phosphorylated tau (p-tau), ubiquitin C-terminal hydrolase L1 (UCH-L1), and hormones. High or moderate bias was found in most studies, and marker-specific conclusions were subject to heterogeneous and limited evidence. Although the evidence is weak, some biofluid markers—such as NfL—appeared to show promise. More markedly, S100B was found to be problematic when evaluating the effects of RSHI in sport. Conclusion: Considering the limitations of the evidence base revealed by this first review dedicated to systematically scoping the evidence of biofluid marker levels following RSHI exposure, the field is evidently still in its infancy. As a result, any recommendation and application is premature. Although some markers show promise for the assessment of brain health following RSHI exposure, future large standardized and better-controlled studies are needed to determine biofluid markers’ utility.

Original languageEnglish
Article number12
JournalSports Medicine - Open
Issue number1
StatePublished - Dec 2024


  • Contact sport
  • Diagnostics
  • Fluid biomarkers
  • Heading
  • Neurodegenerative disease
  • Traumatic brain injury


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