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Biomarkers of HIE in Term Neonates as Predictors of Outcome

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Mona Guo

on 14 November 2013

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Transcript of Biomarkers of HIE in Term Neonates as Predictors of Outcome

Hypoxic-Ischemic Encephalopathy
Most frequent source of brain injury in term infants (>36wks) : 1 - 6 out of 1000
25% die or have multiple disabilities
4% mild-moderate CP
10% developmental delay
Gold Standard

aEEG +/- Evoked Potentials

Clinical Exam
Neurotrophic calcium binding protein released during astrocyte injury
Neurotoxic at high concentrations

Glycolytic enzyme in neurons
Marker of neuronal injury
Detected only if BBB disrupted
Will my baby be OK?
Biomarkers of HIE in Term Neonates as Predictors of Outcome
A Sad Beginning
Diagnosis by ACOG
Metabolic acidosis (cord pH < 7 or base deficit ≥ 12mmol/L)
Early onset encephalopathy in infants born >34wk gestation
Multisystem organ dysfunction
(affected by hypothermia)
What if you're at a small rural hospital without the capabilities to do rapid serial MRs or emergent EEGs?
Limited sensitivity in first 24h

Useful @ 6h but limited by sedation

Unreliable if undergoing hypothermia
Intrapartum hypoxic-ischemic insult strong enough to cause neonatal encephalopathy that subsequently leads to CP

0h: Sensitivity 65% Specificity 84% LR 3.93
72h: Sensitivity 71% Specificity 82% LR 4.05
75 moderate-severe encephalopathic neonates enrolled over 3 yrs
Blood samples for S100B and NSE taken from indwelling umbilical artery or venous line: 0 (time of hypothermia), 12, 24, 72hr
Outcome determined by
MRI at 7-10d and scored according to severity of basal ganglia injuries and watershed
Neurologic exam at discharge or day 14 assessing for significant deficit (abnormality of tone, consciousness, sensory/autonomic function)
Massaro et al
First urine after birth > 1mcg/L predicted neonatal death with Sn/Sp 100%
Cord blood > 2.02ug/L Sn 87% Sp 88% for predicting development of moderate/severe HIE
0h: Sensitivity 71% Specificity 83% LR 4.08
72h: Sensitivity 70% Specificity 88% LR 5.83
Massaro et al
Serum >40mcg/L (obtained 4 - 48h after birth) distinguishes mild/no HIE from mod/severe HIE
Serum >45.4mcg/L distinguishes poor from normal outcomes
Cytoskeletal intermediate filament protein of astrocytes
Released upon death
Glial Fibrillary Acidic Protein
Neuron Specific Enolase
Serum ≥ 0.15ng/mL upon NICU admission predictive of abnormal brain MRI
High serum [] during first 2 days after birth in neonates going through hypothermia correlates with abnormal MRI
Supports survival of existing neurons
Encourages growth and differentiation of new neurons and synapses
Brain-Derived Neurotrophic Factor
Higher cord plasma BDNF levels in neonates with HIE
Will my baby be OK?
Promising biomarkers: NSE, GFAP, BDNF, and S100B
Need more validation with MRI, fMRI EEG, long term developmental follow-up
Allan WC. The clinical spectrum and prediction of outcome in hypoxic-ischemic encephalopathy. Neoreviews 2002; 3: e108-e115
Douglas-Escobar M, Weiss MD. Neonatal biomarkers of brain injury. Neoreviews 2013; 14: e501-e512
Massaro AN, et al. Biomarkers of Brain Injury in Neonatal Encephalopathy Treated with Hypothermia. J Pediatrics 2012; 161(3): 434-440
Nagdyman N, et al. Predictive Value of Brain-Specific Proteins in Serum for Neurodevelopmental Outcome after Birth Asphyxia. Pediatric Research 2003; 54: 270–275
Ramaswamy V, et al. Systematic Review of Biomarkers of Brain Injury in Term Neonatal Encephalopathy. Pediatric Neurology 2009; 40(3): 215-226
Mona Guo
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