Neonatal Seizure Registry, GEnetics of Post-Neonatal Epilepsy

NCT ID: NCT05361070

Last Updated: 2026-02-05

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Total Enrollment: 300 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2022-08-09
• Study Completion Date: 2027-02-28

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.

Conditions

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

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Eligibility Criteria

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

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role: collaborator

University of California, San Francisco

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Hannah C Glass, MDCM, MAS

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Locations

University of California, San Francisco

San Francisco, California, United States

Children's National Medical Center

Washington D.C., District of Columbia, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Boston Children's Hospital

Boston, Massachusetts, United States

University of Michigan

Ann Arbor, Michigan, United States

Duke University

Durham, North Carolina, United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Countries

United States

References

Shellhaas RA, Wusthoff CJ, Numis AL, Chu CJ, Massey SL, Abend NS, Soul JS, Chang T, Lemmon ME, Thomas C, McNamara NA, Guillet R, Franck LS, Sturza J, McCulloch CE, Glass HC. Early-life epilepsy after acute symptomatic neonatal seizures: A prospective multicenter study. Epilepsia. 2021 Aug;62(8):1871-1882. doi: 10.1111/epi.16978. Epub 2021 Jul 2.

Reference Type: BACKGROUND

PMID: 34212365 (View on PubMed)

Numis AL, da Gente G, Sherr EH, Glass HC. Whole-exome sequencing with targeted analysis and epilepsy after acute symptomatic neonatal seizures. Pediatr Res. 2022 Mar;91(4):896-902. doi: 10.1038/s41390-021-01509-3. Epub 2021 Apr 12.

Reference Type: BACKGROUND

PMID: 33846556 (View on PubMed)

Glass HC, Grinspan ZM, Li Y, McNamara NA, Chang T, Chu CJ, Massey SL, Abend NS, Lemmon ME, Thomas C, McCulloch CE, Shellhaas RA; Neonatal Seizure Registry Study Group. Risk for infantile spasms after acute symptomatic neonatal seizures. Epilepsia. 2020 Dec;61(12):2774-2784. doi: 10.1111/epi.16749. Epub 2020 Nov 13.

Reference Type: BACKGROUND

PMID: 33188528 (View on PubMed)

Glass HC, Grinspan ZM, Shellhaas RA. Outcomes after acute symptomatic seizures in neonates. Semin Fetal Neonatal Med. 2018 Jun;23(3):218-222. doi: 10.1016/j.siny.2018.02.001. Epub 2018 Feb 6.

Reference Type: BACKGROUND

PMID: 29454756 (View on PubMed)

Bennett ER, Reuter-Rice K, Laskowitz DT. Genetic Influences in Traumatic Brain Injury. In: Laskowitz D, Grant G, editors. Translational Research in Traumatic Brain Injury. Boca Raton (FL): CRC Press/Taylor and Francis Group; 2016. Chapter 9. Available from http://www.ncbi.nlm.nih.gov/books/NBK326717/

Reference Type: BACKGROUND

PMID: 26583176 (View on PubMed)

Wong VS, Langley B. Epigenetic changes following traumatic brain injury and their implications for outcome, recovery and therapy. Neurosci Lett. 2016 Jun 20;625:26-33. doi: 10.1016/j.neulet.2016.04.009. Epub 2016 May 4.

Reference Type: BACKGROUND

PMID: 27155457 (View on PubMed)

Christensen J, Pedersen MG, Pedersen CB, Sidenius P, Olsen J, Vestergaard M. Long-term risk of epilepsy after traumatic brain injury in children and young adults: a population-based cohort study. Lancet. 2009 Mar 28;373(9669):1105-10. doi: 10.1016/S0140-6736(09)60214-2. Epub 2009 Feb 21.

Reference Type: BACKGROUND

PMID: 19233461 (View on PubMed)

Eriksson H, Wirdefeldt K, Asberg S, Zelano J. Family history increases the risk of late seizures after stroke. Neurology. 2019 Nov 19;93(21):e1964-e1970. doi: 10.1212/WNL.0000000000008522. Epub 2019 Oct 23.

Reference Type: BACKGROUND

PMID: 31645466 (View on PubMed)

Other Identifiers

R01NS124051

Identifier Type: NIH

Identifier Source: secondary_id

View Link

R01NS124051-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

21-35563

Identifier Type: -

Identifier Source: org_study_id