Pryce, JW; (2013) Novel Investigations in Sudden Unexpected Death in Infancy (SUDI). Doctoral thesis , UCL (University College London).

Abstract

Unexplained Sudden Unexpected Death in Infancy (SUDI) is a diagnosis where a definitive cause of death cannot be ascertained. It remains the most common diagnosis in infant death at autopsy, despite the performance of a range of investigations including histology, microbiology and chemical pathology. Of all infant deaths with a demonstrable cause, infection is the most common finding. Recent research has shown that in some cases of unexplained SUDI, there is supportive evidence of an infectious process. Recent advances in diagnostic pathology include immunohistochemistry on formalin-fixed, paraffin-embedded (FFPE) tissue, proteomics and metabolomics. However, there are few techniques, which have transitioned from clinical practice into use during autopsy. Current techniques used at autopsy in cases of sudden infant death were assessed to see whether there was support for an infectious process. This included a retrospective analysis of all infant autopsies performed at a single centre over a fourteen-year period. Also, current consensus opinion was evaluated to determine areas of diagnostic difficulty. Cohort groups of infant deaths were selected for the application of novel immunohistochemical staining and proteomic analysis from FFPE tissues. The findings indicate that infection remains the commonest identifiable cause of death in SUDI, even over a 100 year time period, supported by recent demographic data. Unexplained SUDI cases were confirmed as having an increased incidence of positive blood cultures for infections of uncertain significance, including Staphylococcus aureus and Escherichia Coli. Evaluation of organ weights at autopsy demonstrated no significant associations, although the thymus was smaller in cases of infectious deaths. Blood/bile acylcarnitine levels showed differential expression in 3 different cohorts. Immunohistochemical staining revealed infectious deaths had a characteristic profile of expression including upregulated C Reactive Protein and ICAM-1. Protein expression was investigated with development of an applicable technique for usage in autopsy FFPE tissue. Subsequently, a pilot study of the utilisation of proteomics in the diagnosis of SUDI was performed with effective extraction of peptides and the identification of bacterial proteins in different cohorts. This thesis has demonstrated new techniques for the investigation of SUDI with establishment of supportive evidence for infectious deaths which are applicable for future use in autopsy cases.

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