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.