Early biomarkers to predict grade of encephalopathy following hypoxic ischaemic injury

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dc.contributor.advisor Boylan, Geraldine B. en
dc.contributor.advisor Kenny, Louise C. en
dc.contributor.advisor Murray, Deirdre M. en
dc.contributor.author Walsh, Brian
dc.date.accessioned 2015-08-13T09:05:44Z
dc.date.issued 2014
dc.date.submitted 2014
dc.identifier.citation Walsh, B. 2014. Early biomarkers to predict grade of encephalopathy following hypoxic ischaemic injury. PhD Thesis, University College Cork. en
dc.identifier.uri http://hdl.handle.net/10468/1898
dc.description.abstract The standard early markers for identifying and grading HIE severity, are not sufficient to ensure all children who would benefit from treatment are identified in a timely fashion. The aim of this thesis was to explore potential early biomarkers of HIE. Methods: To achieve this a cohort of infants with perinatal depression was prospectively recruited. All infants had cord blood samples drawn and biobanked, and were assessed with standardised neurological examination, and early continuous multi-channel EEG. Cord samples from a control cohort of healthy infants were used for comparison. Biomarkers studied included; multiple inflammatory proteins using multiplex assay; the metabolomics profile using LC/MS; and the miRNA profile using microarray. Results: Eighty five infants with perinatal depression were recruited. Analysis of inflammatory proteins consisted of exploratory analysis of 37 analytes conducted in a sub-population, followed by validation of all significantly altered analytes in the remaining population. IL-6 and IL-6 differed significantly in infants with a moderate/severely abnormal vs. a normal-mildly abnormal EEG in both cohorts (Exploratory: p=0.016, p=0.005: Validation: p=0.024, p=0.039; respectively). Metabolomic analysis demonstrated a perturbation in 29 metabolites. A Cross- validated Partial Least Square Discriminant Analysis model was developed, which accurately predicted HIE with an AUC of 0.92 (95% CI: 0.84-0.97). Analysis of the miRNA profile found 70 miRNA significantly altered between moderate/severely encephalopathic infants and controls. miRNA target prediction databases identified potential targets for the altered miRNA in pathways involved in cellular metabolism, cell cycle and apoptosis, cell signaling, and the inflammatory cascade. Conclusion: This thesis has demonstrated that the recruitment of a large cohortof asphyxiated infants, with cord blood carefully biobanked, and detailed early neurophysiological and clinical assessment recorded, is feasible. Additionally the results described, provide potential alternate and novel blood based biomarkers for the identification and assessment of HIE. en
dc.description.sponsorship Higher Education Authority (PRTLI cycle 4) en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher University College Cork en
dc.rights © 2014, Brian Walsh en
dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/3.0/ en
dc.subject Biomarker en
dc.subject EEG en
dc.subject HIE en
dc.subject Asphyxia en
dc.subject Neonate en
dc.title Early biomarkers to predict grade of encephalopathy following hypoxic ischaemic injury en
dc.type Doctoral thesis en
dc.type.qualificationlevel Doctoral en
dc.type.qualificationname PhD (Medicine and Health) en
dc.internal.availability Full text not available en
dc.check.info Indefinite en
dc.check.date 10000-01-01
dc.description.version Accepted Version
dc.contributor.funder Molecular Medicine Ireland en
dc.contributor.funder Higher Education Authority en
dc.description.status Not peer reviewed en
dc.internal.school Paediatrics and Child Health en
dc.check.type No Embargo Required
dc.check.reason No embargo required en
dc.check.opt-out Not applicable en
dc.thesis.opt-out false
dc.check.embargoformat Not applicable en
ucc.workflow.supervisor d.murray@ucc.ie


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© 2014, Brian Walsh Except where otherwise noted, this item's license is described as © 2014, Brian Walsh
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