Novel hypothesis for unexplained sudden unexpected death in infancy (SUDI)

Objective: Two recent retrospective studies independently reported typically pathogenic bacteria in normally sterile sites of infants succumbing to sudden unexpected death in infancy (SUDI). These findings suggested a proportion of unexplained SUDI might be triggered by bacteraemia. The objective was to assess these observations in the context of the pathology and epidemiology of sudden infant death syndrome (SIDS) in relation to the role of infection and inflammation as triggers of these deaths. Design: A review of the literature to identify potential risk factors for unexplained infant deaths and proposal of a theoretical model for SUDI. Results: Pathologic and epidemiological evidence suggests a hypothesis based on three factors: bacterial translocation, pathogen pattern recognition insufficiency and prenatal exposure to infection. Conclusion: We propose that sterile site infections in which common toxigenic bacteria are identified indicate a brief bacteraemic episode prior to death. This might reflect an ineffective innate response to invasive pathogens that results in reduced clearance of the bacteria. Thymomegaly observed consistently among infants diagnosed under the category of SIDS might have its origins in prenatal life, perhaps generated via in utero infection or exposure to microbial antigens which results in thymocyte priming. There is consistent evidence for an infectious aetiology in many unexplained SUDI. Future directions for research are suggested.