Clinical Utility of Serum Biomarkers for the Management of Neonatal Hypoxic Ischemic Encephalopathy (Control Levels)
| Status: | Completed |
|---|---|
| Conditions: | Peripheral Vascular Disease, Neurology |
| Therapuetic Areas: | Cardiology / Vascular Diseases, Neurology |
| Healthy: | No |
| Age Range: | Any |
| Updated: | 6/23/2018 |
| Start Date: | March 2016 |
| End Date: | July 2017 |
Clinical Utility of Serum Biomarkers for the Management of Neonatal Hypoxic Ischemic Encephalopathy (HIE) Control Levels
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.
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.
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.
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.
Inclusion Criteria:
- greater than 1.8 kg
- gestational age of 34 weeks or greater
Exclusion Criteria:
- less than 1.8 kg
- gestational age less than 34 weeks
We found this trial at
1
site
University of Florida The University of Florida (UF) is a major, public, comprehensive, land-grant, research...
Click here to add this to my saved trials
