Healthy Little Eyes

Visual Function as a Novel Outcome Measure Following Neonatal Hypoxic Ischemic Encephalopathy

The purpose of this research study is to gather more information on how eye injury is related to a baby's future development and see if eye function and brain test results can be used, along with current measures, to better diagnose and treat babies with hypoxic-ischemic encephalopathy (HIE).

Participants will undergo up to two eye exam sessions, involving both Visual Evoked Potential (VEP) and Electroretinogram (ERG) exams.

Study Overview

• Status: Recruiting
• Conditions: Hypoxic-Ischemic Encephalopathy; Neonatal Encephalopathy; Encephalopathy
• Intervention / Treatment: Device: Visual Evoked Potential (VEP); Device: Electroretinogram (ERG)

• Study Type: Observational
• Enrollment (Estimated): 125

Contacts and Locations

• Study Contact: Name: Alexandra Lindstrom; Phone Number: 608-262-2388; Email: aklindstrom2@wisc.edu

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53705
      • Recruiting
      • University of Wisconsin
      • Contact: Alexandra Lindstrom; Email: aklinidstrom2@wisc.edu
      • Principal Investigator: Pelin Cengiz, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

1. HIE Neonates in the NICU at AFCH or Meriter who are less than 78 hours old
2. HIE Neonates at Waisman, AFCH Newborn Follow-up Clinic, or CERU Clinic who are less than 78 hours old
3. Well babies at the Meriter Newborn Nursery who are less than 36 months of age

Description

HIE Neonate Inclusion Criteria:

• Inpatient Neonates diagnosed with HIE
• Pediatric patients who are less than 78 hours of age at the time of enrollment
• Participants whose parent/legal guardian is able to complete consenting process in English

HIE Neonate Exclusion Criteria:

• Participants with prenatally diagnosed or congenital brain and/or eye abnormalities not associated with HIE, including but not limited to microphthalmia, anophthalmia, congenital cataract, eye or eyelid coloboma, congenital glaucoma, CMV retinitis, optic nerve hypoplasia, aniridia, cryptophthalmos, globe abnormalities
• Participants who have a known central nervous system illness other than HIE, including but not limited to congenital brain malformations or congenital hydrocephalus
• Participants whose parent/legal guardian is unable to provide informed consent, including participants who are in foster care, participants within state custody, and participants of minor parents

Waisman, AFCH NBFU, or CERU Clinic HIE Patient Inclusion Criteria:

• Pediatric patients who have a diagnosis of HIE and present to the Newborn Follow Up Clinic
• Pediatric patients who are less than 36 months of age at the time of enrollment
• Participants whose parent/legal guardian is able to complete consenting process in English

Waisman, AFCH NBFU, or CERU Clinic HIE Patient Exclusion Criteria:

• Participants with prenatally diagnosed or congenital brain and/or eye abnormalities not associated with HIE, including but not limited to microphthalmia, anophthalmia, congenital cataract, eye or eyelid coloboma, congenital glaucoma, CMV retinitis, optic nerve hypoplasia, aniridia, cryptophthalmos, globe abnormalities
• Participants who have a known central nervous system illness not associated with HIE and its complications. Complications may include seizures, hydrocephalus, and stroke, which are NOT exclusionary. Examples of exclusionary conditions include but are not limited to traumatic brain injury outside the perinatal period, meningitis, or diagnosis of brain tumor
• Participants whose parent/legal guardian is unable to provide informed consent, including participants who are in foster care, participants within state custody, and participants of minor parents

Well Baby Inclusion Criteria:

• Patient in Meriter's Newborn Nursery
• ≥37 and <42 weeks gestational age
• 5-minute Apgar Score ≥7
• Occipital Frontal Circumference (OFC) is within average limits for age (<97th percentile and >3rd percentile)

Well Baby Exclusion Criteria:

• Admitted to the NICU for any reason
• Known genetic abnormality
• Diagnosed with HIE
• Diagnosed with Hypoglycemia
• Diagnosed with Hyperbilirubinemia requiring phototherapy
• Identified prenatal exposure to substances, including illicit drugs, alcohol, and/or tobacco
• Known or suspected neonatal infection requiring treatment (e.g., antibiotics)
• TORCH infections
• Abnormal newborn hearing screen
• Abnormal toxicology screening
• Identified as large for gestational age (LGA) or small for gestational age (SGA)
• Participants with prenatally diagnosed or congenital eye abnormalities, including but not limited to microphthalmia, anophthalmia, congenital cataract, eye or eyelid coloboma, congenital glaucoma, CMV retinitis, optic nerve hypoplasia, aniridia, cryptophthalmos, globe abnormalities, and nystagmus
• Subjects who have a known central nervous system illness or malformation, including but not limited to congenital brain malformations or congenital hydrocephalus
• Participants whose parent/legal guardian is unable to provide informed consent, including subjects who are in foster care, subjects within state custody, and subjects of minor parents
• The attending medical team does not approve

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Healthy participants	Device: Visual Evoked Potential (VEP); Small gold-cup electrodes will be placed on the participant's head using a small dot of adhesive paste. The handheld device is then connected to the electrodes, and the participant's eyes are exposed to a light flicker. Each eye will be tested separately, and while testing one eye, the other eye may be patched.; Device: Electroretinogram (ERG); Skin electrodes will be placed under each eye. Eyes will then be exposed to a flashing light. Each eye will be tested separately and while testing one eye, the other eye may be patched.
Participants with HIE	Device: Visual Evoked Potential (VEP); Small gold-cup electrodes will be placed on the participant's head using a small dot of adhesive paste. The handheld device is then connected to the electrodes, and the participant's eyes are exposed to a light flicker. Each eye will be tested separately, and while testing one eye, the other eye may be patched.; Device: Electroretinogram (ERG); Skin electrodes will be placed under each eye. Eyes will then be exposed to a flashing light. Each eye will be tested separately and while testing one eye, the other eye may be patched.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the correlation between retinal function and neurodevelopmental outcomes	The least absolute shrinkage and selection operator technique will be utilized to determine whether ERG measures predict neurodevelopmental outcomes	Through 30 months of life
To evaluate the correlation between retinal function and neuroimaging outcomes	The least absolute shrinkage and selection operator technique will be utilized to determine whether ERG measures predict neuroimaging outcomes	Within first 5 days of life
To evaluate the correlation between visual cortical function and neurodevelopmental outcomes	The least absolute shrinkage and selection operator technique will be utilized to determine whether VEP measures predict neurodevelopmental outcomes	Through 30 months of life
To evaluate the correlation between visual cortical function and neuroimaging outcomes	The least absolute shrinkage and selection operator technique will be utilized to determine whether VEP measures predict neuroimaging outcomes	Within first 5 days of life
Compare ERG results between healthy babies and babies with HIE	The ERG results from healthy babies will be compared to those of babies with HIE	Within first 5 days of life
Report Shape of the VEP results for healthy babies and babies with HIE	The shape of the waveform will be reported as a categorical variable: sharp, slanted, blunt, or multiple peaks	Within first 5 days of life
Compare Amplitude of the VEP results between healthy babies and babies with HIE	The amplitude will be reported as differences in microvolt responses between groups.	Within first 5 days of life
Compare Latency of the VEP results between healthy babies and babies with HIE	The latency will be reported as differences in timing (measured in milliseconds) between groups.	Within first 5 days of life
Compare Transocular Shape, Amplitude, and Latency Difference of the VEP results between healthy babies and babies with HIE	The Transocular Shape Difference will be reported as differences in shape between the two eyes compared across groups, reported as a categorical variable: sharp, slanted, blunt, or multiple peaks.	Within first 5 days of life

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison
• Collaborators: Meriter Foundation
• Investigators: Principal Investigator: Pelin Cengiz, MD, University of Wisconsin, Madison

Study record dates

Study Major Dates

• Study Start (Actual): February 24, 2020
• Primary Completion (Estimated): July 1, 2024
• Study Completion (Estimated): July 1, 2024

Study Registration Dates

• First Submitted: June 27, 2023
• First Submitted That Met QC Criteria: July 24, 2023
• First Posted (Actual): August 2, 2023

Study Record Updates

• Last Update Posted (Actual): August 2, 2023
• Last Update Submitted That Met QC Criteria: July 24, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: neonatal; electroretinogram; visual evoked potential
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Central Nervous System Diseases; Nervous System Diseases; Signs and Symptoms, Respiratory; Hypoxia, Brain; Brain Ischemia; Brain Diseases; Hypoxia; Hypoxia-Ischemia, Brain
• Other Study ID Numbers: 2019-1243; SMPH\PEDIATRICS\PICU (Other Identifier: UW Madison); Protocol Version 3/31/2023 (Other Identifier: UW Madison)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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