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<jats:title>Background<\/jats:title>\n                    <jats:p>Growing evidence indicates that former professional contact sports athletes are at increased risk of neurodegenerative disease, potentially linked to repetitive head impacts (RHI). Research into the acute effects of RHI on fluid biomarkers of neural damage can contribute to the identification of underlying pathophysiological processes. Objectives: To systematically aggregate the acute effect of contact sport participation on fluid biomarkers of neural damage.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>MEDLINE, Embase and SPORTDiscus were searched up to 18 July 2024. Studies that were included assessed fluid biomarkers of neural damage before and within 24\u00a0h after a single session of contact sport participation. Studies on mild traumatic brain injury were excluded. Risk of bias was assessed using the Bias in Non-randomized Studies of Exposure tool and the Risk of Bias Tool 2. The level of evidence was synthesized according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. Meta-analysis was performed for natural and experimental exposure to RHI separately, while also differentiating for contact sports and biomarkers in subsequent analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Thirthy-three studies (representing 892 participants) were included for meta-analysis. Meta-analysis on natural exposure revealed medium-to-large-sized elevations across blood biomarkers for fight sports (\n                      <jats:italic>k<\/jats:italic>\n                      = 7), American Football (\n                      <jats:italic>k<\/jats:italic>\n                      = 9) and football (soccer) (\n                      <jats:italic>k<\/jats:italic>\n                      = 2). Very few studies (8%) controlled for the confounding effects of physical exercise or blood volume change, introducing considerable risk of bias. Meta-analysis on experimental exposure to football heading revealed no significant change in blood biomarkers of neural damage (\n                      <jats:italic>k<\/jats:italic>\n                      = 11,\n                      <jats:italic>n<\/jats:italic>\n                      = 236,\n                      <jats:italic>d<\/jats:italic>\n                      = 0.108, 95% CI = \u22120.047 to 0.263,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.172), and the experimental heading groups also showed no difference in pre\u2013post change compared with control groups (\n                      <jats:italic>k<\/jats:italic>\n                      = 8, heading = 174, controls = 151,\n                      <jats:italic>d<\/jats:italic>\n                      = \u22120.115, 95% CI = \u22120.452 to 0.223,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.505).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The current literature provides convincing evidence for acute elevations of blood biomarkers after a single session of contact sports participation. However, due to considerable risk of bias in existing literature, this evidence is very uncertain regarding the acute effect of contact sports participation on brain integrity (GRADE level of evidence: very low). On the basis of meta-analysis of the available literature (including S100B, neurofilament light chain and total-tau), the evidence is very uncertain about the acute effects of football heading on brain integrity within 24 h after exposure (GRADE level of evidence: very low). In the light of the increased risk of neurodegenerative disease in former professional contact sport athletes, there is a need for well-powered and controlled prospective studies on the acute and long-term effects of contact sport participation on brain integrity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registry<\/jats:title>\n                    <jats:p>PROSPERO number: CRD42023461119.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s40279-026-02529-x","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T16:45:15Z","timestamp":1791305115000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Repetitive Head Impacts During Contact Sports and Fluid Biomarkers of Neural Damage: A Meta-analysis"],"prefix":"10.1007","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3604-1982","authenticated-orcid":false,"given":"Marloes I.","family":"Hoppen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzie","family":"Kamps","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Everard G. 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The work of M.H. and M.K. was funded by the Royal Dutch Football Association. E.V. is a member and M.K. is an unpaid structural consulting expert of the temporary Brain Injury through Sports Committee of the Health Council of the Netherlands. C.T. serves on editorial boards of Medidact Neurologie\/Springer, Alzheimer Research and Therapy, and Neurology: Neuroimmunology & Neuroinflammation.","order":1,"name":"Ethics","label":"Conflicts of Interest","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Data are available in a public repository (DATAVERSE NL:\n                      \n                      [\n                      \n                      ]).","order":2,"name":"Ethics","label":"Data Availability","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"M.H., S.K., E.V., C.T., J.O. and M.K. made substantial contributions to the conception and design of the work; M.H. and J.D. were involved in the acquisition of the data. M.H. and S.K. performed the data extraction and analysis. M.H., S.K., E.V., C.T., J.O. and M.K. were involved in the interpretation of data. M.H. and M.K. drafted the manuscript. All authors revised the manuscript critically for important intellectual content, gave final approval of the version to be published and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.","order":3,"name":"Ethics","label":"Author Contributions","group":{"name":"EthicsHeading","label":"Declarations"}}]}}