Clinical Utility of Serum Biomarkers for the Management of Neonatal Hypoxic Ischemic Encephalopathy (Control Levels)
Condition: Hypoxic Ischemic Encephalopathy
MeSH terms: Brain Diseases; Brain Ischemia; Hypoxia-Ischemia, Brain; Ischemia; Hypoxia
Study type: Observational

Summary: 
      Hypoxic-ischemic encephalopathy (HIE) is a serious birth complication due to systemic
      asphyxia which occurs in about 20 of 1,000 full-term infants and nearly 60% of premature
      newborns. Between 10-60% of babies who exhibit HIE die during the newborn period and up to
      25% of the HIE survivors have permanent neurodevelopmental handicaps in the form of cerebral
      palsy, mental retardation, learning disabilities, or epilepsy. HIE also has a significant
      financial impact on the health care system. In the state of Florida, the total cost for
      initial hospitalization is $161,000 per HIE patient admitted, but those costs don't take into
      account the life-long costs.

      Current monitoring and evaluation of HIE, outcome prediction, and efficacy of hypothermia
      treatment rely on a combination of a neurological exam, ultrasound, magnetic resonance
      imaging (MRI) and electroencephalography (EEG). However, these methods do a poor job in
      identifying non-responders to hypothermia. MRI requires transport of the neonate with a
      requisite 40-45 min scan, which is not appropriate for unstable neonates. Moreover, the
      amplitude integrated EEG (aEEG), a common bedside monitoring technique currently used in
      these patients to assess candidates and predict outcomes prior to hypothermia, can be
      adversely affected by hypothermia itself and the patient may not appear to improve until
      re-warming. Consequently, the development of a simple, inexpensive, non-invasive, rapid
      biochemical test is essential to identify candidates for therapeutic hypothermia, to
      distinguish responders from non-responders and to assess outcome. This research is the first
      step needed to treat neonates with HIE employing a personalized medical approach using serum
      proteins GFAP and UCH-L1 as biomarkers and by monitoring neonates responses to therapeutic
      hypothermia. These biomarkers will aid in the direct care by providing a rapid test to
      predict outcomes and select candidates who are likely to benefit from therapeutic hypothermia
      and gauge a response to the neuroprotective intervention.
    

Detailed description: 
      Control Neonates will be easily obtained from a single center, Shands UF. The control samples
      will be derived from two groups: (1) "Healthy Controls" will be healthy neonates with Apgar
      scores ≥ 7 at 1 minute and ≥ 8 at 5 minutes and no other medical problems associated with
      neurologic injury such as hyperbilirubinemia or hypoglycemia. This group will establish a
      negative control and will have 500-800µL of blood collected at the time of standard blood
      metabolic screens (at 24 and 48 hours of life). (2) "Clinical Controls" will be healthy
      neonates evaluated for jaundice, with multiple blood samples drawn between birth and 48 hours
      of life to monitor serum bilirubin concentrations. They will have an additional 0.8-1 mL of
      blood drawn at the time of any clinical sample (venous or heel stick) is performed. In
      addition, neonates will be excluded if they show signs of sepsis or hypoglycemia (< 40). The
      neonates' bilirubin will be plotted using the American Academy of Pediatrics risk-based
      stratification method, the Bhutani monogram (which is a based on the serum bilirubin
      concentration and the hours of life). Clinical control neonates must have low-risk or
      low-intermediate bilirubin concentrations, with virtually no risk of brain injury.
    

Intervention name(s): blood sample
Intervention type(s): Procedure
Intervention description(s): Blood will be collected to test for concentrations of UCH-L1 and GFAP.
Observational model: Cohort
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        neonates
      
Biospecimen description: 
      blood samples
    
Keywords: HIE; Neonates