Global Epidemiology of Neonatal and Infantile-Onset Epilepsies and Epilepsy Syndromes (GENIE)
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.
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Authors: Mohammed Safeer V S, Akanksha Singh, Najiya Nahan, Priyanka Madaan, Sebastian Friedrich Winter, Manya Prasad, Elaine C. Wirrell, Ravindra Arya, Raidah Albaradie, Gus A. Baker, Derrick W. S. Chan, Alla B. Guekht, Shinichi Hirose, Yuwu Jiang, Wang-Tso Lee, Kheng Seang Lim, Kazuhiro Muramatsu, Kohei Nagai, Kullasate Sakpichaisakul, Pauline Samia, Nicola Specchio, Hasan Tekgül, Chahnez Charfi Triki, Kette D. R. Valente, Jithangi Wanigasinghe, Jo M. Wilmshurst, Ingrid Eileen Scheffer, Judith Helen Cross, Valery Feigin, Jitendra Kumar Sahu, Dipika Bansal
Institutions: University of Washington, Charité – Universitätsmedizin Berlin, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Universidade de São Paulo, The University of Melbourne, Harvard University, KU Leuven, Cincinnati Children's Hospital Medical Center, National Institute for Health and Care Research, Rangsit University, University College London, Istituti di Ricovero e Cura a Carattere Scientifico, National Taiwan University, Post Graduate Institute of Medical Education and Research, University of Cape Town, Ege University, Royal Children's Hospital, Great Ormond Street Hospital, All India Institute of Medical Sciences, Murdoch Children's Research Institute, Austin Health, University of Malaya, Mayo Clinic, National Taiwan University Hospital, Fukuoka University, King Fahad Specialist Hospital, Pirogov Russian National Research Medical University, University of Cincinnati, Jichi Medical University, University of Colombo, National Institute of Pharmaceutical Education and Research, National Institute of Pharmaceutical Education and Research, Mass General Brigham, Auckland University of Technology, University of Sfax, Peking University First Hospital, Bambino Gesù Children's Hospital, Institute for Health Metrics and Evaluation, Austin Hospital, Aga Khan University Nairobi, Red Cross War Memorial Children's Hospital, KK Women's and Children's Hospital, Moscow Research and Clinical Center for Neuropsychiatry, Hopital Universitaire Hedi Chaker, Queen Sirikit National Institute of Child Health, NIHR Great Ormond Street Hospital Biomedical Research Centre, Fondazione Bambino Gesù