Postmortem Tandem Mass Spectrometry Profiling for Detection of Infection in Unexpected Infant Death

Numerous hypotheses have been suggested to explain the cause of sudden unexpected infant death, including infection. As part of the autopsy, routine ancillary investigations are performed, including blood/bile tandem mass spectrometry (TMS) primarily for detection of metabolic disease. The aim of this study was to evaluate and assess TMS derived acylcarnitine profiles to determine whether infectious deaths were associated with characteristic profiles. As part of a retrospective study including >2,500 pediatric autopsies at a single specialist centre over a 14 year period, acylcarnitine profiles were reviewed. Using multiple linear regression, standardised residuals were prepared and findings compared between different cause of death groups, including unexplained, focal infection, microbiological infection and accidental injuries. 415 blood samples from SUDI autopsies were identified. Statistically significant differences in TMS profiles were identified between those dying of infection and the unexplained SUDI group, including changes in free carnitine, short chain acylcarnitines and octanoylcarnitine. Cases with microbiological infection diagnosed only from postmortem cultures did not show any significant difference from the unexplained group. Postmortem TMS profiling identifies SUDI deaths which are associated with histological evidence of infection, and an acylcarnitine profile suggesting perturbation of oxidative metabolism. Such findings raise the possibility that more comprehensive TMS profiling may offer additional diagnostic clues beyond screening for metabolic disorders, and may contribute to determination of mode of death.