Research in context
Evidence before this study
Children have a high incidence of traumatic brain injury (TBI) caused by falls, vehicle crashes, sport participation, and abuse. In preparation for this study, we searched for blood biomarker studies in paediatric TBI in National Centre for Biotechnology Information (USA) databases from Jan 1, 1990, to Sept 30, 2018, using the search terms “traumatic brain injury”, “children OR pediatric”, “blood OR serum OR plasma”, and “biomarker”. Studies were included if participants were aged between 0 and 19 years and one or more blood proteins or metabolites were measured. Studies were excluded if participants were older than 19 years, blood biomarkers were not measured, data were derived from animal models, or if they were not primary publications. Both the number of control participants (if present) and patients with TBI, and type of control group (ie, healthy or orthopaedic injury) were used to ascertain study quality. 165 publications were found, of which 64 remained after applying the exclusion criteria above. 51 studies focused solely on paediatric TBI, and 13 studies compared patients with TBI to control participants (two studies included control children with orthopaedic injury and 11 studies included healthy children as controls). 22 studies included 50 participants or fewer, 12 studies had between 51–100 participants, and 13 studies had more than 100 participants. However, only one study had more than 100 participants in each of the TBI and control groups. Therefore, there are few studies in children that compare a well powered TBI cohort with an equally well powered control group, and valid normative data for paediatric TBI blood biomarkers are not available.
Added value of this study
Our study used a rigorous approach to establish normative data for paediatric serum total tau concentrations that meet the guidelines of the US Clinical and Laboratory Standards Institute. We studied a well powered cohort of healthy children aged 1 to less than 19 years to guide interpretation of changes in serum total tau concentrations in children after TBI. Serum total tau varies by age but not by sex in children. After TBI, serum total tau concentrations were elevated in all patients with a Glasgow Coma Scale (GCS) score below 15 points, could discriminate between patients with mild TBI (GCS 13–14 vs GCS 15), and peaked on the first day of injury, except in patients with severe TBI, in whom it remained elevated for at least 7 days.
Implications of all the available evidence
Serum total tau could help to differentiate patients with various degrees of mild TBI, as its concentrations in patients with GCS scores of 15 points subjects were indistinguishable from those of control participants, whereas concentrations in patients with GCS scores of 13–14 were elevated. Serum total tau at day 1 was not useful for predicting positive radiological findings on CT scans. As serum total tau concentrations vary widely in children younger than 4 years, its diagnostic value for TBI might be weaker in infants and toddlers compared with school-aged children and adolescents.