Exploring serum GFAP and UCH-L1 levels in children with global developmental delay: associations with language impairment and widened extracerebral spaces.

To determine the levels of serum biomarkers of astrocytic (glial fibrillary acidic protein, GFAP) and neuronal (ubiquitin C-terminal hydrolase-L1, UCH-L1) injury in children with global developmental delay (GDD) of non-structural etiology and to investigate their associations with developmental profiles and specific brain magnetic resonance imaging (MRI) phenotypes. In this retrospective cross-sectional study, we included 98 children (median age 38.1 months; 72 males) diagnosed with GDD of non-structural etiology. Serum GFAP and UCH-L1 concentrations were measured. Developmental outcomes were assessed across five domains using the Gesell Developmental Scales. Brain MRI scans (n = 70) were systematically reviewed and categorized for specific structural phenotypes. Serum GFAP and UCH-L1 levels exceeding the laboratory-defined cutoffs were detectable in 74.5% and 42.9% of children, respectively. After adjusting for age and sex, higher GFAP level was independently associated with a lower developmental quotient in the language domain (β = -0.314, P = 0.011). GFAP levels were significantly higher in children with widened extracerebral spaces (P = 0.011). Serum GFAP and UCH-L1 levels exceeding the cutoffs are frequently detectable in GDD of non-structural etiology. The specific association of GFAP with language impairment and widened extracerebral spaces provides measurable evidence of astrocytic involvement in functional and structural alterations. These biomarkers may aid in the biological stratification of GDD, though the findings remain exploratory and require validation in independent cohorts.