Neonatal Seizure Registry, GEnetics of Post-Neonatal Epilepsy

Recruiting

• Conditions: Intracranial Hemorrhage; Epilepsy; Gene Abnormality; Hypoxic-Ischemic Encephalopathy; Stroke; Neonatal Seizure

• Registration Number: NCT05361070
• Lead Sponsor: University of California, San Francisco

Brief Summary

The NSR-GENE study is a longitudinal cohort study of approximately 300 parent-child trios from the Neonatal Seizure Registry and participating site outpatient clinics that aims to evaluate whether and how genes alter the risk of post-neonatal epilepsy among children with acute provoked neonatal seizures. The researchers aim to develop prediction rules to stratify neonates into low, medium, and high risk for post-neonatal epilepsy based on clinical, electroencephalogram (EEG), magnetic resonance imaging (MRI), and genetic risk factors.

Detailed Description

Neonatal seizures due to brain injury (acute provoked seizures) are associated with high risk of post-neonatal epilepsy. Although clinical risk factors can help predict which children are at highest risk for epilepsy, little is known about how genetic factors modify the risk for epilepsy after acute provoked neonatal seizures. The Neonatal Seizure Registry - GENetics of Epilepsy (NSR-GENE) study will test the central hypothesis that children who develop post-neonatal epilepsy are more likely to have pathogenic variants in epilepsy genes, and enrichment in single nucleotide polymorphisms within key inflammatory, neurotransmitter transport and homeostasis, and neurotrophic gene pathways as compared with children who do not develop unprovoked seizures before age five years, and that these can be added to traditional clinical risk factors to predict epilepsy after neonatal seizures.

Study Timeline

• Study First Submitted: 2022-04-29
• Study First Submitted QC: 2022-04-29
• Study First Posted: 2022-05-04
• Study Start: 2022-08-09
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-02
• Last Update Posted: 2025-04-06
• Primary Completion: 2027-02-28
• Study Completion: 2027-02-28

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 300

Inclusion Criteria

• Children < 44 weeks postmenstrual age at seizure onset
• Seizures due to an acute provoked cause (including, but not limited to HIE, ischemic stroke, or intracranial hemorrhage)
• Parent(s) who are English or Spanish literate (with interpreter)
• Birthdate between 3/1/2023 and 1/1/2011
• One biological parent willing to participate
• Enrolled in NSR-II
• Fulfilling all NSR-II eligibility criteria and evaluated at an NSR center for neonatal seizures or enrolled in NSR-RISE

Exclusion Criteria

• Risk for adverse outcome independent of seizures and underlying brain injury (including but not limited to inborn errors of metabolism, fetal infection, brain malformation)
• Transient cause for seizures (e.g., hypoglycemia without brain injury, hyponatremia, hypocalcemia)
• Neonatal-onset epilepsy syndromes
• Deceased

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Number of participants with post-neonatal epilepsy	5 years of age	The presence or absence of a post-neonatal epilepsy diagnosis at age 5 in children with a prior history of acute symptomatic neonatal seizures will be determined by telephone interview with the parent and corroborated by medical record review

Trial Locations

Locations (8)

Boston Children's Hospital; 🇺🇸 Boston, Massachusetts, United States

University of California, San Francisco; 🇺🇸 San Francisco, California, United States

Children's National Medical Center; 🇺🇸 Washington, District of Columbia, United States

Duke University; 🇺🇸 Durham, North Carolina, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Children's Hospital of Philadelphia; 🇺🇸 Philadelphia, Pennsylvania, United States

University of Michigan; 🇺🇸 Ann Arbor, Michigan, United States

Cincinnati Children's Hospital Medical Center; 🇺🇸 Cincinnati, Ohio, United States