SP16. Exploring Serum Biomarkers as Potential Indicators of Brain Injury in Infants With Craniosynostosis

PURPOSE: Craniosynostosis (CS) is a congenital condition characterized by the premature fusion of cranial sutures, leading to abnormal skull growth and potential neurodevelopmental delays. It is not well understood if delays are secondary to intrinsic brain abnormalities or of chronic elevated intra-cranial pressure (ICP). Moreover, some neurocognitive delays persist after surgical correction. Brain health prior to surgery is not systematically characterized due to varying levels of invasiveness, availability, or interpretation of current assessment techniques. This pilot study aims to explore the feasibility and effectiveness of non-invasive markers to assess the brain health of children with craniosynostosis. METHODS: This prospective observational study included 20 infants (7 weeks to 14 months old) diagnosed with CS and 11 age-matched controls undergoing non-CS-related surgeries. Serum samples were collected within 2 days of surgery. Proteomic analysis involved trypsin digestion and separation using a Bruker nano-elute II HPLC system, followed by analysis with Bruker Daltronic tims-tof HT using data-independent acquisition (DIA). The resulting spectra were matched against a human protein database to identify and quantify 277 proteins, categorized by their relevance to brain injury and intracranial pressure (ICP). RESULTS: Patients diagnosed with CS had an average age of 6.3 months with the following affected cranial sutures: metopic, sagittal, coronal, and lambdoid. The control group had an average age of 9.5 months and had no notable health concerns. A preliminary analysis was conducted to compare CS patient protein levels with controls, finding significantly elevated levels of S100 proteins in CS patients: S100-A4 (p = 0.0182), S100-A7 (p = 0.0094), S100-A8 (p = 0.0001), and S100-A9 (p = 0.0007). These proteins are known for their roles in inflammation and neuronal regulation. Notably, several proteins in the literature associated with elevated ICP and brain injury, were not found to have statistically significant elevations in the CS group when compared to the control group in this study’s analysis. CONCLUSION: This study highlights the potential of the S100 protein family as serum biomarkers for detecting brain injury in craniosynostosis patients. Although preliminary, these findings suggest a potential non-invasive biomarker could offer valuable diagnostic insights, and an additional tool to assess the pathophysiology of CS. Further research is needed to confirm their clinical significance and refine their role in patient care in a large, more controlled study.