Exploratory factor analysis yields grouping of brain injury biomarkers significantly associated with outcomes in neonatal and pediatric ECMO
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Updated: Jun 26, 2025
Systems Analysis of the Neuroinflammatory and Hemodynamic Response to Traumatic Brain Injury
Published on: May 27, 2022
Victoria Huang1, Jennifer Roem2, Derek K Ng2
1Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, 1800 Orleans Street, Bloomberg Suite 6321, Baltimore, MD, 21287, USA.
Insights
This study identified three key factors among brain injury biomarkers in children on ECMO (extracorporeal membrane oxygenation). Higher scores in cellular injury and vascular factors predicted worse outcomes, while a neuroplasticity factor suggested better outcomes.
Area of Science:
- Pediatric Neurology
- Biomarker Discovery
- Extracorporeal Membrane Oxygenation (ECMO)
Background:
- Brain injury is a significant concern in children requiring ECMO.
- Identifying reliable biomarkers for predicting outcomes in this population is crucial.
Purpose of the Study:
- To explore the interplay of plasma brain injury biomarkers in pediatric ECMO patients.
- To assess the association of these biomarkers with clinical outcomes.
Main Methods:
- Prospective cohort study involving 95 children on ECMO at two centers.
- Daily measurement of 11 plasma brain injury biomarkers for the first 3 days.
- Exploratory Factor Analysis (EFA) to group biomarkers and multivariable logistic regression to assess outcome associations.
Main Results:
- EFA identified three distinct biomarker factors: cellular injury (Factor 1), vascular processes (Factor 2), and a BDNF/MMP-9 pathway (Factor 3).
- Higher Factor 1 and Factor 2 scores were significantly associated with increased odds of unfavorable composite outcomes (mortality or significant neurodevelopmental decline).
- Higher Factor 3 scores were associated with decreased odds of unfavorable outcomes, potentially linked to neuroplasticity.
Conclusions:
- EFA effectively grouped plasma brain injury biomarkers in pediatric ECMO patients.
- The identified biomarker factors show significant association with clinical outcomes.
- These factors hold potential as prognostic instruments for guiding clinical management in pediatric ECMO.
Abstract:
In this two-center prospective cohort study of children on ECMO, we assessed a panel of plasma brain injury biomarkers using exploratory factor analysis (EFA) to evaluate their interplay and association with outcomes. Biomarker concentrations were measured daily for the first 3 days of ECMO support in 95 participants. Unfavorable composite outcome was defined as in-hospital mortality or discharge Pediatric Cerebral Performance Category > 2 with decline ≥ 1 point from baseline. EFA grouped 11 biomarkers into three factors. Factor 1 comprised markers of cellular brain injury (NSE, BDNF, GFAP, S100β, MCP1, VILIP-1, neurogranin); Factor 2 comprised markers related to vascular processes (vWF, PDGFRβ, NPTX1); and Factor 3 comprised the BDNF/MMP-9 cellular pathway. Multivariable logistic models demonstrated that higher Factor 1 and 2 scores were associated with higher odds of unfavorable outcome (adjusted OR 2.88 [1.61, 5.66] and 1.89 [1.12, 3.43], respectively). Conversely, higher Factor 3 scores were associated with lower odds of unfavorable outcome (adjusted OR 0.54 [0.31, 0.88]), which is biologically plausible given the role of BDNF in neuroplasticity. Application of EFA on plasma brain injury biomarkers in children on ECMO yielded grouping of biomarkers into three factors that were significantly associated with unfavorable outcome, suggesting future potential as prognostic instruments.
