The HIEnome Study: Genome Sequencing for Perinatal HIE

Perinatal hypoxic-ischemic encephalopathy is a rare severe condition in which neonates present with encephalopathy and a clinical history suggestive of prenatal or perinatal hypoxic-ischemic injury. Emerging evidence suggests that genetic conditions are frequently identified in cases of perinatal HIE; however, it is unclear which neonates with this diagnosis warrant genetic testing. This study will offer clinical genome sequencing to neonates with HIE who are undergoing total body cooling (therapeutic hypothermia) and their parents.

Study Overview

• Status: Recruiting
• Conditions: Hypoxic Ischemic Encephalopathy; Hypoxic Ischemic Encephalopathy of Newborn; Hypoxic Ischemic Encephalopathy (HIE)
• Intervention / Treatment: Genetic: Genome sequencing

• Study Type: Interventional
• Enrollment (Estimated): 25
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Christian Parobek, MD, PhD; Phone Number: 828-713-9962; Email: christian.parobek@bcm.edu
• Study Contact Backup: Name: Seema Lalani, MD; Phone Number: 7137988921; Email: seemal@bcm.edu

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • Texas Children's Hospital
      • Contact: Christian Parobek, MD, PhD; Phone Number: 828-713-9962; Email: christian.parobek@bcm.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Delivery ≥35w0d gestation
• Diagnosed with moderate or severe HIE, or HIE with seizures
• Undergoing total body cooling / therapeutic hypothermia
• Able to provide blood or buccal samples during birth hospitalization
• Admitted to Texas Children's Hospital Main, West, or Woodlands NICU

Exclusion Criteria:

• Parents/family not willing to allow participation
• Inability to collect sufficient neonatal blood samples (in some circumstances, a buccal swab may be used as backup)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Perinatal HIE; Newborns diagnosed with moderate or severe perinatal hypoxic-ischemic encephalopathy (HIE) who are undergoing therapeutic hypothermia will receive genome sequencing to identify co-morbid genetic conditions. Participants' genetic data will be analyzed for copy number variations (CNVs), single nucleotide variants (SNVs), and triplet repeat disorders per ACMG reporting standards.

Genetic: Genome sequencing; Neonates enrolled in this study will undergo genome sequencing with parental controls as applicable.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic yield	The primary outcome will be the number of cases with a pathogenic or likely-pathogenic variant associated with encephalopathy. This will further be stratified by the presence or absence of a perinatal hypoxic insult or sentinel event.	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Genome versus exome sequencing	A secondary outcome will be the incremental improvement in genome sequencing versus simulated exome testing. Diagnostic variants will be classified by their genomic location: exonic, intronic, or deep intronic. The rate of diagnostic findings in genomic locations that would be assayed by exome sequencing will be compared to the overall diagnostic rate (including variants in intronic regions that would not be detected on exome sequencing) to determine the incremental diagnostic benefit of genome sequencing over exome sequencing in this population.	18 months
Indeterminate results	A secondary outcome will be the identification rate of non-diagnostic / indeterminate results in genes linked to conditions with an overlapping neuromuscular or neurodevelopmental phenotype.	18 months

Collaborators and Investigators

• Sponsor: Baylor College of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): May 15, 2025
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: December 20, 2024
• First Submitted That Met QC Criteria: January 6, 2025
• First Posted (Actual): January 8, 2025

Study Record Updates

• Last Update Posted (Estimated): October 1, 2025
• Last Update Submitted That Met QC Criteria: September 25, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Genetic testing; Genome sequencing; Hypoxic-ischemic encephalopathy
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Brain Ischemia; Signs and Symptoms, Respiratory; Hypoxia, Brain; Hypoxia; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Hypoxia-Ischemia, Brain
• Other Study ID Numbers: H-54168

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: No
• product manufactured in and exported from the U.S.: No