Early biomarkers to predict grade of encephalopathy following hypoxic ischaemic injury

dc.check.date10000-01-01
dc.check.embargoformatNot applicableen
dc.check.infoIndefiniteen
dc.check.opt-outNot applicableen
dc.check.reasonNo embargo requireden
dc.check.typeNo Embargo Required
dc.contributor.advisorBoylan, Geraldine B.en
dc.contributor.advisorKenny, Louise C.en
dc.contributor.advisorMurray, Deirdre M.en
dc.contributor.authorWalsh, Brian
dc.contributor.funderMolecular Medicine Irelanden
dc.contributor.funderHigher Education Authorityen
dc.date.accessioned2015-08-13T09:05:44Z
dc.date.issued2014
dc.date.submitted2014
dc.description.abstractThe 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.sponsorshipHigher Education Authority (PRTLI cycle 4)en
dc.description.statusNot peer revieweden
dc.description.versionAccepted Version
dc.format.mimetypeapplication/pdfen
dc.identifier.citationWalsh, B. 2014. Early biomarkers to predict grade of encephalopathy following hypoxic ischaemic injury. PhD Thesis, University College Cork.en
dc.identifier.urihttps://hdl.handle.net/10468/1898
dc.language.isoenen
dc.publisherUniversity College Corken
dc.rights© 2014, Brian Walshen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/en
dc.subjectBiomarkeren
dc.subjectEEGen
dc.subjectHIEen
dc.subjectAsphyxiaen
dc.subjectNeonateen
dc.thesis.opt-outfalse
dc.titleEarly biomarkers to predict grade of encephalopathy following hypoxic ischaemic injuryen
dc.typeDoctoral thesisen
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnamePhD (Medicine and Health)en
ucc.workflow.supervisord.murray@ucc.ie
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