Sudden unexpected deaths in children: distinct entities.

Sudden unexpected deaths in early life have historically been grouped under broad, inconsistent terminology, limiting epidemiologic precision and mechanistic understanding. Standardized investigation and surveillance now permit clearer differentiation among distinct entities. The goal of this project is to synthesize epidemiologic, forensic, and molecular evidence supporting classification of sudden unexpected postnatal collapse (SUPC), sudden unexpected infant death (SUID), and sudden unexpected death in childhood (SUDC) as distinct entities, and to examine whether shared biologic vulnerability underlies cases across age groups. A narrative review used population-based epidemiologic studies, national and international surveillance data, forensic pathology reports, and molecular autopsy investigations, emphasizing standardized definitions, age-stratified analyses, and comprehensive death-scene investigation. SUPC is rare, occurs almost exclusively within the first postnatal week, and is linked to early caregiving context during physiologic transition. SUID is more common (approximately 101 per 100,000 US live births in 2022), peaks at 1 to 4 months, and shows robust associations with modifiable sleep-environment factors. SUDC is rare, occurs predominantly after age 1, and lacks consistent environmental risk factors; data suggest contributions from autonomic instability or seizure susceptibility. Molecular autopsy studies in SUID and SUDC have identified variants in genes governing cardiac conduction, autonomic regulation, and neuronal excitability, suggesting shared intrinsic vulnerability in a subset, though cohorts remain small. Conclusions: SUPC, SUID, and SUDC are distinct entities warranting separate classification and prevention strategies. Emerging but limited molecular data support further investigation of cross-age biologic vulnerability. Accurate classification, standardized investigation, and molecular integration are needed to advance the field.