Global Epidemiology of Neonatal and Infantile-Onset Epilepsies and Epilepsy Syndromes (GENIE)

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.

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Journal
JAMA Neurology
Published
2026-11-02
DOI
https://doi.org/10.1001/jamaneurol.2026.3906
Primary Topic
Epilepsy research and treatment
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article
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article

Global Epidemiology of Neonatal and Infantile-Onset Epilepsies and Epilepsy Syndromes (GENIE)

Judith Helen Cross, Ravindra Arya, Jo M. Wilmshurst, Kette D. R. Valente et al.
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JAMA Neurology
Epilepsy research and treatment
article

Global Epidemiology of Neonatal and Infantile-Onset Epilepsies and Epilepsy Syndromes (GENIE)

Judith Helen Cross, Ravindra Arya, Jo M. Wilmshurst, Kette D. R. Valente, Kheng Seang Lim, Akanksha Singh, Sebastian Friedrich Winter, Pauline Samia, Jitendra Kumar Sahu, Mohammed Safeer V S, Kullasate Sakpichaisakul, Hasan Tekgül, Jithangi Wanigasinghe, Gus A. Baker, Ingrid Eileen Scheffer, Kohei Nagai, Alla B. Guekht, Nicola Specchio, Elaine C. Wirrell, Priyanka Madaan, Kazuhiro Muramatsu, Dipika Bansal, Derrick W. S. Chan, Manya Prasad, Raidah Albaradie, Najiya Nahan, Wang-Tso Lee, Valery Feigin, Yuwu Jiang, Shinichi Hirose, Chahnez Charfi Triki
article en

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.

JAMA Neurology
Cincinnati Children's Hospital Medical Center (US), Royal Children's Hospital (AU), Mayo Clinic (US), Harvard University (US), University of Sfax (TN), Jichi Medical University (JP), University of Cape Town (ZA), The University of Melbourne (AU), National Taiwan University (TW), Universidade de São Paulo (BR), University of Washington (US), Great Ormond Street Hospital (GB), Austin Hospital (AU), King Fahad Specialist Hospital (SA), Institute for Health Metrics and Evaluation (US), Fukuoka University (JP), Pirogov Russian National Research Medical University (RU), University of Malaya (MY), National Institute for Health and Care Research (GB), Auckland University of Technology (NZ), Ege University (TR), Queen Sirikit National Institute of Child Health (TH), Moscow Research and Clinical Center for Neuropsychiatry (RU), Aga Khan University Nairobi (KE), Hopital Universitaire Hedi Chaker (TN), KK Women's and Children's Hospital (SG), Bambino Gesù Children's Hospital (IT), Peking University First Hospital (CN), National Taiwan University Hospital (TW), Berlin Institute of Health at Charité - Universitätsmedizin Berlin (DE), National Institute of Pharmaceutical Education and Research (IN), Murdoch Children's Research Institute (AU), National Institute of Pharmaceutical Education and Research (IN), Istituti di Ricovero e Cura a Carattere Scientifico (IT), Red Cross War Memorial Children's Hospital (ZA), Austin Health (AU), NIHR Great Ormond Street Hospital Biomedical Research Centre (GB), Fondazione Bambino Gesù (IT), University College London (GB), Post Graduate Institute of Medical Education and Research (IN), Mass General Brigham (US), University of Cincinnati (US), All India Institute of Medical Sciences (IN), Charité - Universitätsmedizin Berlin (DE), Rangsit University (TH), University of Colombo (LK), KU Leuven (BE)
Good health and well-being
Openalex Percentile: Top 14%
Epilepsy research and treatment
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