Global, regional and national burden of epilepsy secondary to four major neonatal disorders: insights from the Global Burden of Disease Study 2021.

Background: Neonatal disorders are increasingly recognized as critical contributors to lifelong neurological disability, yet comprehensive global assessments of their impact on secondary epilepsy remain limited. This study aimed to analyze the long-term global burden, regional disparities, and etiological patterns of epilepsy secondary to four major neonatal disorders: preterm birth, sepsis, encephalopathy, and hemolytic disease. Methods: Using data from the Global Burden of Disease Study 2021, we assessed the prevalence, years lived with disability (YLDs), and age-standardized rates of epilepsy attributable to the four major neonatal disorders from 1990 to 2021. Trends were quantified with estimated annual percentage change. Associations with the Socio-demographic Index (SDI) were evaluated using Spearman's correlation and inequality analysis. Frontier analysis explored efficiency in prevention, and decomposition analysis identified key drivers of YLD changes. Results: In 2021, epilepsy cases from these neonatal disorders reached 22.1 million, accounting for 42.7% of all epilepsy cases globally. The age-standardized prevalence rate (ASPR) increased to 286.0 per 100,000 population. The burden exhibited significant disparities: higher in males at younger ages but shifting to females in older groups, and peaked in childhood. South Asia and the Caribbean had the highest burdens. Neonatal preterm birth was the dominant cause globally, but neonatal encephalopathy due to birth asphyxia and trauma led in East Asia, while neonatal sepsis and other neonatal infections was primary in Eastern Europe. The correlation between disease burden and SDI varied markedly by etiology and metric: ASPR was positively correlated with SDI for preterm birth, sepsis, and encephalopathy, but negatively for hemolytic disease; patterns for age-standardized YLD rate (ASYR) were more heterogeneous. Inequality patterns varied by etiology. Population growth was the primary driver of increasing YLDs. Conclusions: Epilepsy secondary to major neonatal disorders constitutes a substantial and growing global health burden, marked by significant regional, etiological, and socioeconomic disparities. Targeted strategies are urgently needed, focusing on high-burden regions, addressing shifting epidemiological patterns, and expanding rehabilitation services to mitigate disability and reduce inequalities.