Age-Dependent Differences in Blood Levels of Glial Fibrillary Acidic Protein but Not Ubiquitin Carboxy-Terminal Hydrolase L1 in Children

Neurology. 2024 Aug 13;103(3):e209651. doi: 10.1212/WNL.0000000000209651. Epub 2024 Jul 10.

Abstract

Objectives: Despite the growing evidence of the clinical utility of blood-brain biomarkers in adults with traumatic brain injury (TBI), less is known about the performance of these biomarkers in children. We characterize age-dependent differences in levels of ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) in children without TBI.

Methods: Plasma biobank specimens from children and adolescents aged 0-<19 years without TBI were obtained, and UCH-L1 and GFAP levels were quantified. The relationship between age and biomarker expression was determined using previously defined aged epochs (<3.5 years, 3.5 years to <11 years, 11 years and older), then biomarker levels were compared with established thresholds for ruling out the need for a head CT in adults with a mild TBI (mTBI) (UCH-L1 400 pg/mL, GFAP 35 pg/mL).

Results: The age range of the 366 control patients was 3 months-18 years. There was a significant negative association between age and GFAP but not UCH-L1. Only 1.4% of samples exceeded the UCH-L1 cutoff; however, 20% of samples exceeded the GFAP cutoff and 100% children younger than 3.5 years had values that exceeded the cutoff.

Discussion: Age seems to modify physiologic plasma GFAP levels. Diagnostic cutoffs for TBI based on GFAP but not UCH-L1 and may need to be adjusted in children younger than 11 years.

MeSH terms

  • Adolescent
  • Age Factors
  • Biomarkers* / blood
  • Child
  • Child, Preschool
  • Female
  • Glial Fibrillary Acidic Protein* / blood
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Ubiquitin Thiolesterase* / blood

Substances

  • Ubiquitin Thiolesterase
  • Glial Fibrillary Acidic Protein
  • Biomarkers
  • UCHL1 protein, human
  • GFAP protein, human