Biomarkers for Detection of Brain Ischemia
Condition: Congenital Disorders
MeSH terms: Brain Ischemia; Ischemia
Study type: Observational

Summary: 
      Brain injury occurs in one-quarter to one-half of congenital heart defect infants during the
      perioperative period. A blood test using a biomarker to diagnose brain injury would be
      important.

      Postoperative cerebral ischemia may be decreased by inotropic support, ventilation, medical
      management aimed at increasing oxygen delivery to the brain. Currently there are no FDA
      approved blood tests to assess brain ischemia in infants undergoing cardiac surgery.

      Specific Aim 1: We will prospectively study 10 neonates (< 30 days of age) undergoing cardiac
      surgery utilizing cardiopulmonary bypass for arterial switch operation or Norwood operation
      to determine the specificity and sensitivity of a blood test for brain injury. This aim will
      be accomplished by analyzing blood samples for S-100 and NSE drawn prior to surgery, once
      each day following cardiac surgery as long as the patient remains in the intensive care unit
      (maximum 5 days)and at the time of postoperative brain magnetic resonance imaging. The S-100B
      and NSE values will then be correlated with brain magnetic resonance imaging studies before
      cardiac surgery and at following cardiac surgery.

      Hypothesis: We expect the concentration of S-100B and NSE will be significantly higher in the
      blood of neonates with congenital heart disease who have documented brain injury on brain
      magnetic resonance imaging (MRI). Furthermore, we predict that the blood levels of S-100B and
      NSE may correlate to clinical outcome (time to extubation, hospital discharge,
      neurodevelopmental outcome at 6 months of age).

      Specific Aim 2: We will prospectively study these neonates at 6 months following cardiac
      surgery to determine a correlation between neurodevelopment and concentration of S-100B and
      NSE. To achieve this specific aim, a blood sample for S-100B and NSE and neurodevelopmental
      testing will be done at 6 months following cardiac surgery.

      Hypothesis: We expect neonates with elevated S-100B and NSE and abnormal brain magnetic
      resonance imaging documented in specific aim 1 to have a significant decline in
      neurodevelopment at 6 months after cardiac surgery.

      Long-term: The long-term goal of this research is to diagnose brain ischemia in infants using
      a biomarker blood test.
    

Detailed description: 
      1. Ten full-term neonates (> 36 week gestation), between 1-30 days of age, who present for
           arterial switch operation or Norwood operation will have 2 ml of blood drawn prior to
           cardiac surgery, 2 ml blood drawn each day after cardiac surgery as long as the patient
           remains in the intensive care unit with indwelling lines (maximum of 5 days) and 2 ml
           blood drawn on the day of the followup brain magnetic resonance imaging study (if not
           within the maximum of 5 days) to determine blood concentrations S100B and NSE.

        2. Brain magnetic resonance imaging (MRI) including T1, 2, DWI, spectroscopy, and magnetic
           resonance angiography, will be performed prior to cardiac surgery and following cardiac
           surgery in all study patients. Timing of the follow-up brain magnetic resonance imaging
           including T1, 2, DWI, spectroscopy, and magnetic resonance angiography, will be based on
           stability of the patient as assessed by the attending physician. Optimal timing for
           brain magnetic resonance imaging is 4 days postop.

        3. Maternal information including level of education, medications, and medical history will
           be obtained. Two mls of blood will also be obtained from the mother to determine
           maternal blood concentrations of S100B and NSE.

        4. Study patient clinical variables, including vital signs (heart rate, blood pressure,
           respiratory rate), systemic oxygen saturation by extremity pulse oximetry, near infrared
           spectroscopy (NIRS), routine laboratory values will be obtained at the time of each
           study blood sample.

        5. Operative variables including cardiopulmonary bypass time, aortic cross clamp time,
           circulatory arrest time, and hematocrit on bypass will be obtained. Transfusion quantity
           of packed red blood cells, fresh frozen plasma, platelets, and cryoprecipitate used in
           the operating room and in the cardiac intensive care unit will also be obtained

        6. Outcome variables including length of mechanical ventilation, hospital stay, and gross
           neurological abnormalities (clinical seizures) will be obtained.

           Follow-up:

        7. All patients will have neurodevelopmental testing at 6 months after heart surgery.

        8. Another 2 mls of blood S100B and NSE will be obtained when the patient returns at 6
           months for neurodevelopmental testing.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Ten consecutive full-term (>36 week gestation) neonates, one day to 30 days of age,
        presenting for cardiac surgery for arterial switch operation or Norwood operation will be
        eligible for the study
      
Keywords: biomarkers; brain ischemia; neonates; cardiac surgery; congenital heart disease