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Updated: May 13, 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 periventricular white matter injury
Amanda Stewart1, Aylin Tekes, Thierry A G M Huisman
1Division of Maternal-Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University, Baltimore, MD.
Insights
Early detection of periventricular white matter injury (PWMI) in premature infants is possible using glial fibrillary acidic protein (GFAP) blood tests. Elevated GFAP levels shortly after birth can predict PWMI, enabling timely intervention.
Area of Science:
- Neonatal neurology
- Biomarker discovery
- Neurodevelopmental disorders
Background:
- Periventricular white matter injury (PWMI) is a significant precursor to cerebral palsy in low birthweight infants.
- Traditional diagnosis of PWMI via head ultrasound occurs late, at 6 weeks of life, delaying crucial interventions.
Purpose of the Study:
- To investigate the potential of early neonatal glial fibrillary acidic protein (GFAP) levels to identify PWMI in infants with low birthweight.
- To establish a rapid diagnostic method for PWMI shortly after birth.
Main Methods:
- A case-control study matched infants with confirmed PWMI to controls based on gestational age and delivery mode.
- Glial fibrillary acidic protein (GFAP) levels were measured in cord blood and daily from birth up to day 4 of life.
Main Results:
- Significantly elevated GFAP levels were observed in infants who developed PWMI on days 1-4 after birth compared to controls.
- Increased GFAP levels from day 1-4 were strongly associated with a higher likelihood of developing PWMI, even after adjusting for confounding factors.
- No significant difference in GFAP levels was found at birth or upon neonatal intensive care unit admission.
Conclusions:
- Early postnatal measurement of GFAP in blood can effectively predict the development of PWMI in low birthweight infants.
- This blood test offers a pathway for rapid identification of at-risk infants, facilitating early intervention and improved neurodevelopmental outcomes.
- GFAP serves as a valuable biomarker for qualifying new therapeutic interventions aimed at mitigating PWMI.
Objective:
Periventricular white matter injury (PWMI), a precursor of cerebral palsy, traditionally is not diagnosed until 6 weeks of life by head ultrasound scanning. We sought to determine whether early neonatal glial fibrillary acidic protein (GFAP) levels could identify PWMI in low birthweight (<2500 g) infants.
Study Design:
Each case with PWMI on head ultrasound scanning at 6 weeks of life from April 2009 to April 2011 was matched by gestational age and mode of delivery to 2 subsequent neonates with a normal head ultrasound scan. GFAP was measured in cord blood at birth, at neonatal intensive care unit admission, and on days 1-4 of life.
Results:
During this 2-year period, 21 cases with PWMI with gestational age 27.4 ± 3.3 weeks were compared with 42 control infants. The incidence of cesarean delivery was 61.9% in both groups. GFAP was not significantly different in cord blood or at neonatal intensive care unit admission but was significantly elevated on day 1 (median, 5-95%; 0, 0-0.98 ng/mL cases; 0, 0-0.06 ng/mL control infants; P = .03), day 2 (0, 0-1.21 ng/mL; 0, 0-0.05 ng/mL, respectively; P = .02), day 3 (0.05, 0-0.33 ng/mL; 0, 0-0.04 ng/mL, respectively; P = .004), and day 4 (0.02, 0-1.03 ng/mL; 0, 0-0.05 ng/mL, respectively; P < .001). The odds of the development of PWMI significantly increased with increasing levels of GFAP from day 1-4 of life when adjustment was made for preeclampsia, antenatal steroid administration, and neonatal chronic lung disease.
Conclusion:
The ability to predict PWMI with a blood test for GFAP shortly after birth opens the possibility for rapid identification of infants for early intervention and provides a benchmark for the qualification of new therapies to improve neurodevelopmental outcomes.

