Clinical Utility of Serum Biomarkers for the Management of Neonatal Hypoxic Ischemic Encephalopathy (Control Levels)

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.

Study Overview

• Status: Completed
• Conditions: Hypoxic Ischemic Encephalopathy
• Intervention / Treatment: Procedure: blood sample

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.

• Study Type: Observational
• Enrollment (Actual): 39

Contacts and Locations

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 day to 3 days (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

neonates

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Healthy Control; The healthy control group will have 500-800uL (less than 1 mL) of blood collected. This sample will be obtained at the same time that the neonate is already having a standard blood screenings drawn at 24 and 48 hours of life.	Procedure: blood sample; Blood will be collected to test for concentrations of UCH-L1 and GFAP.
Clinical Control; The clinical control group will be healthy neonates that are being evaluated for jaundice, with multiple blood samples drawn between birth and 48 hours of life to monitor serum bilirubin. With these already scheduled lab draws, we will draw an additional 0.8-1 mL of blood.	Procedure: blood sample; Blood will be collected to test for concentrations of UCH-L1 and GFAP.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Levels of UCH-L1 in blood	Determining if UCH-L1 concentrations measured in neonates with HIE are significantly elevated as compared to controls. Evaluate serum biomarker concentrations from a cohort of neonatal HIE patients who are candidates for hypothermia. These samples will be compared to samples collected from the two cohorts of neonatal "control" subjects.	72 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Levels of GFAP in blood	Determining if GFAP concentrations measured in neonates with HIE are significantly elevated as compared to controls. Evaluate serum biomarker concentrations from a cohort of neonatal HIE patients who are candidates for hypothermia. These samples will be compared to samples collected from the two cohorts of neonatal "control" subjects.	72 hours

Collaborators and Investigators

• Sponsor: University of Florida
• Collaborators: American Heart Association
• Investigators: Study Chair: Nicole R Copenhaver, RN, Study nurse UF Neonatology; Study Chair: Melissa Huene, RN, Study nurse UF Neonatology

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2016
• Primary Completion (Actual): June 1, 2017
• Study Completion (Actual): July 1, 2017

Study Registration Dates

• First Submitted: January 23, 2015
• First Submitted That Met QC Criteria: January 28, 2015
• First Posted (Estimate): January 29, 2015

Study Record Updates

• Last Update Posted (Actual): June 21, 2018
• Last Update Submitted That Met QC Criteria: June 20, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Keywords: HIE; Neonates
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Central Nervous System Diseases; Nervous System Diseases; Signs and Symptoms, Respiratory; Hypoxia, Brain; Brain Ischemia; Ischemia; Brain Diseases; Hypoxia; Hypoxia-Ischemia, Brain
• Other Study ID Numbers: IRB201400671

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No