Hidden and Under-Recognized Causes of Sudden Unexpected Death in Infancy (SUDI): A Comprehensive Review of Autopsy Findings

Sudden unexpected death in infancy (SUDI) remains a major challenge in pediatric pathology and forensic medicine. Despite advances in diagnostic techniques, many cases are still classified as unexplained and labeled as sudden infant death syndrome (SIDS). Increasing evidence suggests that a proportion of these deaths may be due to “hidden” causes not detectable through routine post-mortem examination. A narrative review of the literature (2000–2026) was conducted using PubMed and Scopus, focusing on under-recognized causes of SUDI and their diagnostic implications. Relevant studies were selected and organized into major pathological and forensic categories. Hidden causes of SUDI include a wide spectrum of conditions. Cardiac disorders—such as myocarditis, cardiomyopathies, and inherited arrhythmogenic syndromes—are frequently implicated and may require molecular autopsy for detection. Infectious diseases, often presenting with minimal or nonspecific findings, represent another important category, particularly viral and bacterial infections. Inborn errors of metabolism, especially fatty acid oxidation defects, may lead to sudden death in the absence of specific autopsy findings, highlighting the role of biochemical analyses. Neuropathological abnormalities involving brainstem regulatory systems may contribute to impaired autonomic control. Environmental, toxicological, and medico-legal factors—including unsafe sleep conditions, toxic exposures, and inflicted injury—must also be considered. SUDI is a multifactorial entity in which many unexplained deaths may be attributable to identifiable but overlooked conditions. A standardized, multidisciplinary approach integrating autopsy, ancillary investigations, and molecular diagnostics is essential to improve diagnostic accuracy and support prevention strategies.