Sudden infant death syndrome : A medico-legal study of related cardiovascular, toxilogical and genetic findings

Abstract: The present medico-legal investigation of the deaths of infants less than one year of age was designed to enhance our understanding of the Sudden Infant Death Syndrome (SIDS). Special emphasis was placed on the significance of cardiovascular pathology (including heart weight, malformations and myocarditis); exposure to nicotine; and mutations and/or polymorphisms in mitochondrial DNA (mtDNA). A total of 505 infants investigated at the Department of Forensic Medicine in Stockholm, between 1980 and 2001 were studied retrospectively. Body weight was found to be the best indicator of heart weight. A reference table for assessment of the heart weight as a function of the body weight is presented. Heart weights of SIDS victims did not differ from that of the other infants, with the exception of cardiovascular malformations. However, the data do strongly suggests that an increased heart weight, particularly greater than the 75th percentile, should be regarded as an exclusion criterion for SIDS. Congenital cardiovascular malformations (CCMs) were present in 18 infants (3.9 %) of the infants involved in this study. Surprisingly, 67 % of these CCMs, which were either the single, or the contributing cause of death were not diagnosed prior to death. The fact that undiagnosed and most likely operable CCMs as a cause of sudden unexpected death in apparently healthy infants indicates a need for more frequent examinations during the postnatal period. Myocarditis was detected in 16.8 % of natural deaths and 7.4 % of violent deaths. This condition was acute in 46, and chronic in 25 infants. Approximately 35 % of the infants with CMV exhibited myocarditis. With regards to fatality, the location of the inflammatory cells appeared to be more important than the number of foci. Foci of inflammatory cells in the interatrial septum and upper part of the interventricular septum appear to be most lethal, probably because parts of the conduction system are present in this area. High pericardial fluid levels of nicotine and cotinine were detected frequently among infants who slept with their parents and such high levels of nicotine correlated positively with signs of otitis media. In infants exhibiting high levels of cotinine, more focal necrosis and inflammatory changes were observed in the myocardium and liver. Unlike the other infants, approximately 25 % of the SIDS infants demonstrated high levels of cotinine, indicating exposure to nicotine before death. In a sudden infant death where the routine post-mortem examinations failed to establish a cause of death and who exhibited high levels of nicotine and/or cotinine, the infant's exposure to nicotine may have caused or contributed to the fatal outcome. The entire mitochondrial genome of 6 SIDS infants and shorter regions of this organellar DNA in additional 14 SIDS infants were analysed. No specific mutation or polymorphism associated with SIDS was detected. Thus, sequencing of the entire mitochondrial genome in sudden infant deaths, as a diagnostic tool, does not at present appear to provide useful information in the majority of SIDS infants. In conclusion, the sudden infant deaths seem to comprise a mixed group of pathophysiological mechanisms and disorders. The results illustrate the importance of meticulous death investigations -including systematic histopathology with special emphasis on cardiovascular alterations, as well as toxicological screening including nicotine and cotinine and microbiological analyses -- for reliable diagnose and determination of the cause of death.