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Published on: March 26, 2019
Plasma Biomarkers of Brain Injury in Critically Ill Children Receiving Extracorporeal Membrane Oxygenation
Matthew L Friedman1, Michael J Bell2, Bonnie A Brooks3
1Department of Pediatrics, Indiana University School of Medicine, Indianapolis.
Insights
Elevated glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) levels in children on extracorporeal membrane oxygenation (ECMO) can predict acute brain injury (ABI) and poor outcomes.
Area of Science:
- Pediatric Neurology
- Neurocritical Care
- Biomarker Discovery
Background:
- Acute brain injury (ABI) in children on extracorporeal membrane oxygenation (ECMO) requires timely identification for neuroprotection.
- Plasma biomarkers may offer early detection of ABI during ECMO.
Purpose of the Study:
- To investigate if glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), and tau levels predict new ABI in pediatric ECMO patients.
- To assess the association of these biomarkers with mortality and functional outcomes.
Main Methods:
- Prospective observational cohort study (2019-2023) of 219 children (2 days to <18 years) on ECMO.
- Serial plasma GFAP, NfL, and tau measurements during ECMO.
- Correlation with neuroimaging-confirmed ABI and 18-month functional outcomes.
Main Results:
- GFAP and NfL levels significantly increased in the 24 hours preceding new ABI diagnosis.
- Higher GFAP, NfL, and tau levels were associated with unfavorable short-term outcomes.
- A 2-fold increase in GFAP and NfL from baseline predicted unfavorable outcomes, independent of other factors.
Conclusions:
- GFAP and NfL show promise as real-time biomarkers for neurologic monitoring in pediatric ECMO.
- These biomarkers may aid in ABI diagnosis, outcome prediction, and guiding neuroprotective strategies.
Importance:
Timely identification of acute brain injury (ABI) in children receiving extracorporeal membrane oxygenation (ECMO) support is critical for early neuroprotective interventions.
Objectives:
To determine if elevations in plasma glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), and tau levels in children receiving ECMO precede new ABI confirmed by neuroimaging, and if they are associated with mortality and functional outcomes.
Design, Setting, And Participants:
This was a prospective observational cohort study conducted from 2019 to 2023, with 18-month follow-up completed in 2025. Children aged 2 days to younger than 18 years at ECMO cannulation were recruited from 11 US children's hospitals. Study data were analyzed from May to August 2025.
Exposures:
GFAP, NfL, and tau measured in plasma samples collected serially during the ECMO course.
Main Outcomes And Measures:
Unfavorable short-term outcome was a composite of in-hospital mortality or discharge Pediatric Cerebral Performance Category score of 3 or greater with decline of at least 1 point from baseline. Unfavorable long-term outcome was a composite of mortality or Vineland Adaptive Behavior Scales, third edition, composite score less than 85 at 18 months after ECMO.
Results:
This study included 219 participants (224 ECMO courses; 1089 serial blood samples). Median age was 11 months (IQR, 30 days-9 years), and 121 (54%) were male. Among 60 ECMO courses with new ABI during the ECMO course, GFAP and NfL levels increased significantly, by 6.4% (95% CI, 1.4%-11.6%) and 16.1% (95% CI, 10.5%-22.0%), respectively, for each 24 hours preceding neuroimaging diagnosis of new ABI. Geometric means for GFAP, NfL, and tau were all significantly higher in those with unfavorable vs favorable outcome at hospital discharge for both the first sample receiving ECMO and peak levels during ECMO support. A 2-fold increase in GFAP and NfL levels from first sample receiving ECMO was significantly associated with unfavorable outcome after adjusting for baseline GFAP and NfL levels, age, and ECMO indication (GFAP adjusted hazard ratio [aHR], 1.48; 95% CI, 1.22-1.79; NfL aHR, 1.43; 95% CI, 1.14-1.79). Similar models for tau showed no significant association with outcomes.
Conclusions And Relevance:
Results suggest that GFAP and NfL may be promising candidates for real-time neurologic monitoring in children receiving ECMO and may aid in diagnosis, association with outcomes, and potentially guiding neuroprotective strategies.
