Profiles and Predictors of Neurodevelopmental Outcome at 5-6 Years in Children With a History of Acute Provoked Neonatal Seizures

Authors

Hannah C. Glass, Department of Neurology and Weill Institute for Neuroscience, University of California San Francisco, San Francisco, CA, USA.
Adam L. Numis, Department of Neurology and Weill Institute for Neuroscience, University of California San Francisco, San Francisco, CA, USA.
Janet S. Soul, Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Courtney J. Wusthoff, Department of Neurology, University of California Davis Health, Sacramento, CA, USA.
Monica E. Lemmon, Department of Pediatrics and Population Health Sciences, Duke University School of Medicine, Durham, NC, USA.
Giulia M. Benedetti, Department of Pediatrics, C. S. Mott Children's Hospital and the University of Michigan, Ann Arbor, MI, USA.
Catherine J. Chu, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Shavonne L. Massey, Department of Neurology and Pediatrics, Children's Hospital of Philadelphia and Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Philadelphia, PA, USA.
Cameron Thomas, Department of Pediatrics, University of Cincinnati College of Medicine Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Tayyba Anwar, Department of Neurology and Pediatrics, Children's National Hospital and The George Washington University School of Medicine, Washington, DC, USA.
Julie Sturza, Department of Pediatrics, C. S. Mott Children's Hospital and the University of Michigan, Ann Arbor, MI, USA.
Madison M. Berl, Department of Psychiatry and Behavioral Sciences, Children's Research Institute, Children's National Hospital, George Washington University, Washington, DC, USA.
Yi Li, Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, USA.
Elizabeth E. Rogers, Department of Pediatrics, UCSF Benioff Children's Hospital, University of California San Francisco, San Francisco, CA, USA.
Stephanie Rau, Department of Physical Medicine and Rehabilitation, Division of Rehabilitation Psychology Neuropsychology, University of Michigan, Ann Arbor, MI, USA.
Jennifer C. Gidley Larson, Department of Physical Medicine and Rehabilitation, Division of Rehabilitation Psychology Neuropsychology, University of Michigan, Ann Arbor, MI, USA.
Jennifer L. Guerrero, Neonatal Seizure Registry Parent Advisory Panel Member, Division of Breast Surgery, Department of Surgery, Brigham and Women's Hospital, Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, MA, USA.
Linda S. Franck, Department of Pediatrics, UCSF Benioff Children's Hospital, University of California San Francisco, San Francisco, CA, USA.
Charles E. McCulloch, Department of Epidemiology & Biostatistics, University of California San Francisco, San Francisco, CA, USA.
Renée A. Shellhaas, Department of Neurology, Washington University School of Medicine, St Louis, MO, USA.

Document Type

Journal Article

Publication Date

1-3-2026

Journal

Annals of neurology

DOI

10.1002/ana.78100

Abstract

OBJECTIVE: The objective of this study was to characterize the neurodevelopment and risk factors for impairment at age 5 to 6 years after acute provoked neonatal seizures. METHODS: Multicenter study of neonates with acute provoked seizures. Wechsler Preschool and Primary Scale of Intelligence IV (WPPSI-IV), Vineland-3 Adaptive Behavior Scales, Behavior Assessment System for Children, Behavior Rating Inventory of Executive Function, Social Responsiveness Scale, cerebral palsy (CP), and epilepsy were assessed at age 5 to 6 years. Latent class analysis defined outcome profiles. Least absolute shrinkage and selection operator (LASSO) was used to determine outcome predictors. RESULTS: We characterized 3 latent classes among 164 children: (1) Typical Development (63%); (2) Behavioral Dysregulation (13%; low likelihood of physical impairment or severely impaired cognition, high likelihood of attention deficit hyperactivity disorder [ADHD]); and (3) Multi-Domain Impairment (24%; high likelihood of epilepsy and impairment across all domains). Among 144 children with standardized testing, mean WPPSI-IV was 91 ± 25 and Vineland-3 Adaptive Behavior Composite 90 ± 20. Twenty-nine percent had ADHD or elevated attention/hyperactivity scores; 19% had autism or elevated Social Responsiveness scores; 20% had epilepsy, and 19% had CP. Risk factors for Multi-Domain Impairment were abnormal neonatal neurologic examination (odds ratio [OR] = 3.94, 95% confidence interval [CI] = 1.74-8.95), impaired functional development at age 24 months (OR = 3.82, 95% CI = 1.25-11.66), and CP (OR = 3.71, 95% CI = 1.74-7.90). No neonatal or infant characteristics were significantly associated with Behavioral Dysregulation. INTERPRETATION: Nearly two-thirds of 5 to 6-year-old children with provoked neonatal seizures had typical development. Yet, executive and behavioral dysregulation were prevalent, even with preserved cognitive and physical function. These findings can inform outcome discussions and interventions to promote neurodevelopment. ANN NEUROL 2026.

APA Citation

Glass, Hannah C.; Numis, Adam L.; Soul, Janet S.; Wusthoff, Courtney J.; Lemmon, Monica E.; Benedetti, Giulia M.; Chu, Catherine J.; Massey, Shavonne L.; Thomas, Cameron; Anwar, Tayyba; Sturza, Julie; Berl, Madison M.; Li, Yi; Rogers, Elizabeth E.; Rau, Stephanie; Gidley Larson, Jennifer C.; Guerrero, Jennifer L.; Franck, Linda S.; McCulloch, Charles E.; and Shellhaas, Renée A., "Profiles and Predictors of Neurodevelopmental Outcome at 5-6 Years in Children With a History of Acute Provoked Neonatal Seizures" (2026). GW Authored Works. Paper 8622.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/8622

Department

Psychiatry and Behavioral Sciences