IL6 in Combination with Either NfL, NTproBNP, or GFAP to Safely Discharge Children with Mild Traumatic Brain Injury

Mild traumatic brain injury (mTBI) in children is a public health concern resulting in one of the main causes of pediatric emergency department (PED) visits. However, the acute care of mTBI patients remains challenging due to the limited use of specific and safe diagnostic tools. The objective of the study was to evaluate the performance of combined blood biomarkers in distinguishing between children with mTBI who had intracranial injuries (ICI) visible on CT scans and required hospitalization and those who did not. The aim was to safely discharge children with mTBI by ruling out the need for unnecessary CT scans and decreasing the length of stay in observation for symptoms monitoring in the PED. This was a prospective multicenter cohort study of children aged 0-16 years who presented to the PED within 24 h of sustaining mTBI. Blood was drawn at admission, and levels of IL6, neurofilament light (NfL) chain protein, N-terminal prohormone of brain natriuretic peptide (NTproBNP), glial fibrillary acidic protein (GFAP), IL10, S100 calcium-binding protein B, and heart fatty acid binding protein were analyzed. Biomarker performances to identify patients without ICIs were evaluated through receiver operating characteristic curves, where sensitivity was set at 100%. Patients were dichotomized into two groups: (1) with ICI on CT (=CT+) and (2) without ICI on CT or kept in observation without CT (=CT- and Obs.). All CT scans were reviewed by the same pediatric radiologist, following Pediatric Emergency Care Applied Research Network criteria to identify the presence of ICI. Biomarker age correlation was assessed in a healthy group of children aged 0-16 years. 419 children with mTBI and 99 healthy children were enrolled. Twenty-three percent (n = 97/419) of children underwent CT scan examination, while the other (n = 322/419) were kept in observation at the PED. Nineteen percent (n = 18/97) of the children who underwent a CT scan had ICI (=CT+), corresponding to four percent of all mTBI included patients. All the single and duplex combinations of blood-biomarkers were tested for their capacity to safely rule out ICI. IL6 was present in the three best combinations, reaching 100% sensitivity (SE) and with the highest associated specificity (SP). IL6 + NfL yielded 61% SP, followed by IL6 + NTproBNP with 60% SP, and IL6 + GFAP with 57% SP. Neither IL6 nor NTproBNP was found to be age correlated. IL6 in combination with either NfL, NTproBNP, or GFAP could safely rule out 61% of children without ICI (corresponding to 33/79 unnecessary CT scans and 212/322 observation stays at PED). Blood panels incorporating IL6 show promise as decision-making tools for the acute management of children with mTBI. However, further external studies are required to validate these findings.