Global Epidemiology of Neonatal and Infantile-Onset Epilepsies and Epilepsy Syndromes (GENIE): A Systematic Review and Meta-Analysis

Safeer V S M 1 , Singh A 1 , Nahan N 1 , Madaan P 2 , Winter SF 3 , Prasad M 4 Show all authors , Wirrell EC 5 , Arya R 6 , Albaradie R 7 , Baker GA 8 , Chan D 9 , Guekht A 10 , Hirose S 11 , Jiang Y 12 , Lee WT 13 , Lim KS 14 , Muramatsu K 15 , Nagai K 15 , Sakpichaisakul K 16 , Samia P 17 , Specchio N 18 , Tekgul H 19 , Triki CC 20 , Ramos Valente KD 21 , Wanigasinghe J 22 , Wilmshurst J 23 , Scheffer IE 24 , Cross JH 25 , Feigin V 26 , Sahu JK 2 , Bansal D 1

Affiliations 

  • 1 Department of Pharmacy Practice and Clinical Research, National Institute of Pharmaceutical Education and Research, SAS Nagar, India
  • 2 Pediatric Neurology Unit-II, Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India
  • 3 Division of Neuro-Oncology, Mass General Brigham Cancer Institute, Harvard Medical School, Boston, Massachusetts
  • 4 Centre for Community Medicine, All India Institute of Medical Science, New Delhi, India
  • 5 Division of Child and Adolescent Neurology, Department of Neurology, Mayo Clinic, Rochester, Minnesota
  • 6 Comprehensive Epilepsy Center, Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
  • 7 King Fahad Specialist Hospital, Dammam, Saudi Arabia
  • 8 International Bureau for Epilepsy, Washington, DC
  • 9 KK Women's and Children's Hospital, Singapore
  • 10 Moscow Research and Clinical Center for Neuropsychiatry, Moscow, Russia
  • 11 General Medical Research Center School of Medicine, Fukuoka University, Fukuoka, Japan
  • 12 Children's Medical Center, Peking University First Hospital, Beijing, China
  • 13 Department of Pediatric Neurology, National Taiwan University Children's Hospital, Taipei, Taiwan
  • 14 Division of Neurology, Department of Medicine, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia
  • 15 Department of Pediatrics, Jichi Medical University, Shimotsuke City, Tochigi, Japan
  • 16 Department of Pediatrics, Queen Sirikit National Institute of Child Health, Ministry of Public Health, College of Medicine, Rangsit University, Bangkok, Thailand
  • 17 Department of Paediatrics, Medical College, Aga Khan University, Nairobi, Kenya
  • 18 Neurology, Epilepsy, and Movement Disorders Unit, Bambino Gesu Children's Hospital, Full Member of European Reference Network for Rare and Complex Epilepsies, Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy
  • 19 Ege University Medical School, Izmir, Türkiye
  • 20 Department of Child Neurology, Hedi Chaker Hospital, Research Laboratory LR19ES15, University of Sfax, Sfax, Tunisia
  • 21 Center for Research, Pediatric Neurology, University of São Paulo, São Paulo, Brazil
  • 22 Department of Paediatrics, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka
  • 23 Department of Paediatric Neurology, Red Cross War Memorial Children's Hospital, Neuroscience Institute, University of Cape Town, Cape Town, South Africa
  • 24 The University of Melbourne, Austin Health, and Royal Children's Hospital, Florey and Murdoch Children's Research Institutes, Melbourne, Victoria, Australia
  • 25 University College London Great Ormond Street Institute of Child Health, National Institute for Health and Care Research Great Ormond Street Hospital for Children Biomedical Research Centre, London, United Kingdom
  • 26 National Institute for Stroke and Applied Neurosciences, School of Community and Public Health Studies, Auckland University of Technology, Auckland, New Zealand
JAMA Neurol, 2026 Nov 02.
PMID: 42970304 DOI: 10.1001/jamaneurol.2026.3906

Abstract

IMPORTANCE: Despite the profound impact of neonatal and infantile-onset epilepsies on neurodevelopmental outcomes and mortality, consolidated global epidemiological evidence remains lacking.

OBJECTIVES: To estimate the global incidence and prevalence of neonatal and infantile-onset epilepsies and epilepsy syndromes and to characterize their associated etiological profiles.

DATA SOURCES: PubMed, Embase, Web of Science, and Scopus were searched from inception through December 18, 2025.

STUDY SELECTION: Population-based observational studies reporting the incidence or prevalence of neonatal and infantile-onset epilepsies or epilepsy syndromes were eligible for inclusion.

DATA EXTRACTION AND SYNTHESIS: Two authors independently and in duplicate performed study selection, data extraction, and quality assessment of included studies using the Joanna Briggs Institute Critical Appraisal checklist for prevalence studies. Generalized linear mixed-model random-effects meta-analysis was used to pool the estimates of incidence, prevalence, and etiology. Subgroup meta-analyses were conducted by country, World Health Organization (WHO) region, World Bank income, and diagnostic criteria. Metaregression was used to investigate the association between study-level covariates and pooled incidence estimates of infantile-onset epilepsy syndromes.

MAIN OUTCOMES AND MEASURES: Cumulative incidence and prevalence of neonatal and infantile-onset epilepsies and epilepsy syndromes.

RESULTS: A total of 86 population-based studies from 30 countries across 4 WHO regions were included. The pooled cumulative incidence of infantile-onset epilepsies within the first 2 years of life was 236.0 cases (95% CI, 164.7-338.2; 95% prediction interval [PI], 53.0-1044.3) per 100 000 live births. Among epilepsy syndrome subgroups, developmental and epileptic encephalopathies (DEEs) had the highest incidence at 67.7 cases (95% CI, 42.1-108.9; 95% PI, 7.1-636.1) per 100 000 live births. Infantile epileptic spasms syndrome (IESS) was the most incident DEE, with 31.6 cases (95% CI, 27.5-36.2; 95% PI, 13.7-72.6) per 100 000 live births. Among self-limited epilepsies, self-limited infantile epilepsy had the highest incidence at 13.0 cases (95% CI, 9.2-18.2; 95% PI, 6.4-26.4) per 100 000 live births. Subgroup analyses revealed limited geographical representativeness, with the majority of studies from high-income countries in the European Region.

CONCLUSIONS AND RELEVANCE: The findings underscore a significant global burden of neonatal and infantile-onset epilepsies, primarily driven by DEEs, specifically IESS. Given substantial between-study heterogeneity, the pooled estimates should be interpreted as broad indicators rather than precise, generalizable rates. Geographic disparities, with a lack of data from the African and Eastern Mediterranean Regions, underscore the need for population-based studies in underrepresented regions and longitudinal research on survival, remission, and functional outcomes.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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