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Updated: Mar 26, 2026
Experimental Approaches for Biochemical Analysis of Glial Fibrillary Acidic Protein and Its Disease-associated Variants
Published on: November 28, 2025
Glial fibrillary acidic protein as a biomarker for brain injury in neonatal CHD
Stephanie L McKenney1, Fahad F Mansouri2, Allen D Everett2
11Department of Pediatrics,Division of Neonatology,Johns Hopkins University School of Medicine,Baltimore,Maryland,United States of America.
Insights
Glial fibrillary acidic protein (GFAP) did not show significant perinatal brain injury in neonates with critical congenital heart disease (CHD). A trend for elevated GFAP was observed by day 4 in neonates with left heart obstruction.
Area of Science:
- Neonatal Neurology
- Pediatric Cardiology
- Biomarker Research
Background:
- Neonates with critical congenital heart disease (CHD) often exhibit preoperative brain injury, but its timing remains unclear.
- Glial fibrillary acidic protein (GFAP) is a potential biomarker for acute perinatal brain injury.
Purpose of the Study:
- To assess acute perinatal brain injury in neonates with critical CHD using serum GFAP levels.
- To investigate the correlation between GFAP levels and specific types of CHD.
Main Methods:
- Serum GFAP was measured in neonates with CHD (n=56) and two control groups (non-brain-injured and brain-injured newborns) over the first 4 days of life.
- Statistical comparisons included Kruskal-Wallis, Dunn's multiple comparisons, Student's t-test, and chi-squared test.
Main Results:
- Overall GFAP levels did not significantly differ between CHD patients and healthy controls.
- By day 4, 12.5% of CHD neonates had detectable GFAP, compared to 0% of controls.
- A trend towards elevated day 4 GFAP was noted in the left heart obstruction group (50%) compared to other CHD types.
Conclusions:
- GFAP monitoring showed no significant evidence of peripartum brain injury in neonates with critical CHD.
- A trend for elevated GFAP by day 4 in neonates with left heart obstruction suggests potential utility in specific CHD subtypes.
- This pilot study indicates GFAP monitoring may aid in optimizing preoperative care and neuroprotection for high-risk neonates with certain CHDs.
Abstract:
Neonates with critical CHD have evidence, by imaging, of preoperative brain injury, although the timing is unknown. We used circulating postnatal serum glial fibrillary acidic protein as a measure of acute perinatal brain injury in neonates with CHD. Glial fibrillary acidic protein was measured on admission and daily for the first 4 days of life in case and control groups; we included two control groups in this study - non-brain-injured newborns and brain-injured newborns. Comparisons were performed using the Kruskal-Wallis test with Dunn's multiple comparisons, Student's t-test, and χ2 test of independence where appropriate. In aggregate, there were no significant differences in overall glial fibrillary acidic protein levels between CHD patients (n=56) and negative controls (n=23) at any time point. By day 4 of life, 7/56 (12.5%) CHD versus 0/23 (0%) normal controls had detectable glial fibrillary acidic protein levels. Although not statistically significant, the 5/10 (50%) left heart obstruction group versus 1/17 (6%) conoventricular, 0/13 (0%) right heart, and 1/6 (17%) septal defect patients trended towards elevated levels of glial fibrillary acidic protein at day 4 of life. Overall, glial fibrillary acidic protein reflected no evidence for significant peripartum brain injury in neonates with CHD, but there was a trend for elevation by postnatal day 4 in neonates with left heart obstruction. This pilot study suggests that methods such as monitoring glial fibrillary acidic protein levels may provide new tools to optimise preoperative care and neuroprotection in high-risk neonates with specific types of CHD.
