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Updated: Jul 3, 2026
Non-invasive Optical Measurement of Cerebral Metabolism and Hemodynamics in Infants
Published on: March 14, 2013
Blood-Based Biomarkers Predict Cerebral Palsy and Cognitive Delay in Hypoxic-Ischemic Encephalopathy: A Secondary
Danielle Clifford Mrcpi1, Conor L Vaughan2, Seán J Costelloe3
1Infant Centre, University College Cork, Cork, Ireland; Department of Pediatrics and Child Health, University College Cork, Cork, Ireland.
Insights
Blood biomarkers, particularly Tau on day 2, can predict cerebral palsy (CP) in infants with hypoxic-ischemic encephalopathy (HIE). Tau also showed prognostic value for cognitive/language delay, similar to MRI scans.
Area of Science:
- Neonatal neurology
- Biomarker research
- Neurodevelopmental disorders
Background:
- Hypoxic-ischemic encephalopathy (HIE) is a major cause of neonatal brain injury.
- Cerebral palsy (CP) and cognitive/language delays are significant long-term consequences of HIE.
- Early prediction of neurodevelopmental outcomes is crucial for timely intervention.
Purpose of the Study:
- To investigate the predictive value of blood-based biomarkers for CP and cognitive/language delay in infants with moderate-to-severe HIE.
- To compare biomarker performance with neuroimaging (MRI) for outcome prediction.
- To identify specific biomarkers that can be measured in the early days of life.
Main Methods:
- Secondary analysis of the HEAL Trial involving 180 infants with moderate-severe HIE.
- Blood biomarker measurements at baseline, day 2, and day 4 of life.
- Assessment of CP diagnosis and Bayley III cognitive/language scores at 2 years; MRI performed on days 4-6.
Main Results:
- Five biomarkers (Tau, GFAP, VEGF, MIP-1b, IL-13) were altered in infants who developed CP.
- Tau on day 2 showed high accuracy (AUC 0.902) for CP prediction, comparable to MRI.
- Different biomarkers predicted cognitive/language delay, with Tau on day 2 being the best predictor (AUC 0.669).
Conclusions:
- Tau measured on day 2 of life is a highly effective blood biomarker for predicting CP in infants with HIE.
- Biomarker patterns differ for predicting CP versus cognitive/language delay.
- Early blood biomarker assessment offers a promising, non-invasive tool for prognostication in HIE.
Objective:
To determine whether blood-based biomarkers in the first days of life could specifically predict cerebral palsy (CP) and/or cognitive/language delay in infants with moderate-severe hypoxic-ischemic encephalopathy (HIE).
Study Design:
A secondary analysis of the High-dose Erythropoietin for Asphyxia and Encephalopathy trial, which examined erythropoietin as an adjunct to therapeutic hypothermia for moderate-severe HIE. Recruitment took place in the United States from 2017-2019. Analysis focused on 180 infants with biomarker measurements performed at baseline, day 2, and day 4 of life. Outcomes assessed were: a diagnosis of CP at 2 years and Bayley III cognitive/language scores <85 and, separately, <70 at 2 years. Magnetic resonance imaging (MRI) of the brain was performed on day 4-6 of life.
Results:
Mean gestational age was 39.0 weeks and 68 (44%) were female. After adjusting for multiple comparisons, 5 biomarkers: total tubulin-associated protein (Tau), glial fibrillary acidic protein, vascular endothelial growth factor, macrophage inflammatory protein 1b, and interleukin-13 were significantly altered in the CP group. On day 2 of life, Tau resulted in a receiver operating characteristic area under the curve (AUC) of 0.902 (95% CI: 0.812-0.992), specificity 91%, and sensitivity 88%, performing as well as detailed MRI scoring (AUC: 0.90 [95% CI: 0.80-1.0]). A different set of biomarkers showed altered expression in those with cognitive/language delay; Tau, ubiquitin carboxy-terminal hydrolase L1, S100 calcium-binding protein B, and neuron-specific enolase, with the best prediction seen with Tau on day 2 of life (AUC: 0.669 [95% CI: 0.564-0.774], sensitivity 40%, specificity 92%).
Conclusions:
Tau on day 2 of life demonstrated excellent prognostic value for CP in this cohort with moderate-severe HIE and gave similar prediction to detailed MRI score on day of life 4-6. Patterns of neurospecific biomarker perturbations were different for the prediction of cognitive/language delay, but Tau on day 2 remained the best performing biomarker.
Trial Registration:
ClinicalTrials.gov NCT02811263.
