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

Journal articles  - Journal Article, Multicenter Study
Glass, HC; Numis, AL; Soul, JS; Wusthoff, CJ; Lemmon, ME; Benedetti, GM; Chu, CJ; Massey, SL; Thomas, C; Anwar, T; Sturza, J; Berl, MM; Li, Y ...
Published in: Ann Neurol
March 2026

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;99:777-791.

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Published In

Ann Neurol

DOI

EISSN

1531-8249

Publication Date

March 2026

Volume

99

Issue

3

Start / End Page

777 / 791

Location

United States

Related Subject Headings

  • Seizures
  • Risk Factors
  • Neurology & Neurosurgery
  • Neurodevelopmental Disorders
  • Male
  • Infant, Newborn
  • Humans
  • Female
  • Child, Preschool
  • Child
 

Citation

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Chicago
ICMJE
MLA
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Glass, H. C., Numis, A. L., Soul, J. S., Wusthoff, C. J., Lemmon, M. E., Benedetti, G. M., … Shellhaas, R. A. (2026). Profiles and Predictors of Neurodevelopmental Outcome at 5-6 Years in Children With a History of Acute Provoked Neonatal Seizures. Ann Neurol, 99(3), 777–791. https://doi.org/10.1002/ana.78100
Glass, Hannah C., Adam L. Numis, Janet S. Soul, Courtney J. Wusthoff, Monica E. Lemmon, Giulia M. Benedetti, Catherine J. Chu, et al. “Profiles and Predictors of Neurodevelopmental Outcome at 5-6 Years in Children With a History of Acute Provoked Neonatal Seizures.Ann Neurol 99, no. 3 (March 2026): 777–91. https://doi.org/10.1002/ana.78100.
Glass HC, Numis AL, Soul JS, Wusthoff CJ, Lemmon ME, Benedetti GM, et al. Profiles and Predictors of Neurodevelopmental Outcome at 5-6 Years in Children With a History of Acute Provoked Neonatal Seizures. Ann Neurol. 2026 Mar;99(3):777–91.
Glass, Hannah C., et al. “Profiles and Predictors of Neurodevelopmental Outcome at 5-6 Years in Children With a History of Acute Provoked Neonatal Seizures.Ann Neurol, vol. 99, no. 3, Mar. 2026, pp. 777–91. Pubmed, doi:10.1002/ana.78100.
Glass HC, Numis AL, Soul JS, Wusthoff CJ, Lemmon ME, Benedetti GM, Chu CJ, Massey SL, Thomas C, Anwar T, Sturza J, Berl MM, Li Y, Rogers EE, Rau S, Gidley Larson JC, Guerrero JL, Franck LS, McCulloch CE, Shellhaas RA. Profiles and Predictors of Neurodevelopmental Outcome at 5-6 Years in Children With a History of Acute Provoked Neonatal Seizures. Ann Neurol. 2026 Mar;99(3):777–791.
Journal cover image

Published In

Ann Neurol

DOI

EISSN

1531-8249

Publication Date

March 2026

Volume

99

Issue

3

Start / End Page

777 / 791

Location

United States

Related Subject Headings

  • Seizures
  • Risk Factors
  • Neurology & Neurosurgery
  • Neurodevelopmental Disorders
  • Male
  • Infant, Newborn
  • Humans
  • Female
  • Child, Preschool
  • Child