Unmasking immunodeficiency in sudden infant deaths: no evidence of hidden immune disorders.

Introduction: Sudden infant death syndrome (SIDS) remains a leading cause of post-neonatal mortality, yet its underlying mechanisms are largely unknown. Evidence suggests that immune dysfunction may play a role in a subset of cases. However, the role of inborn errors of immunity (IEI), particularly severe combined immunodeficiency (SCID), has not been systematically explored. We aimed to study their potential role in SIDS and infant deaths from infectious disease. Methods: We obtained mortality data for 2012-2017 from The Norwegian Cause of Death Registry and identified eligible infants by reviewing ICD-10 codes for infection-related deaths or SIDS. The medical history and autopsy reports were reviewed and infants with predisposition to infection were excluded. Genetic testing was performed on biobanked newborn dried blood spot samples following the protocol for identifying SCID/IEI in live-born infants. Results: The study population consisted of 79 infants, of which 66% ( Discussion: No missed cases of SCID/IEI were identified among infants who died from infections or SIDS. Yet a significant proportion of the cohort may carry genetic predispositions due to the presence of immune-related genetic variants. Even in the absence of overt immunodeficiency, these findings may reflect a latent vulnerability interacting with physiological and environmental factors.