Early biomarkers to predict grade of encephalopathy following hypoxic ischaemic injury

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.

Using parent report to assess bilingual vocabulary acquisition: a model from Irish

This chapter describes the adaptation of a parent report instrument on early language development to a bilingual context. Beginning with general issues of adapting tests to any language, particular attention is placed on the issue of using parents as evaluators of child language acquisition of a minority language in a bilingual context. In Ireland, Irish is the first official language and is spoken by about 65,000 people on a daily basis. However all Irish speakers are bilingual, and children are exposed to the dominant English language at an early age. Using an adaptation of a parent report instrument, 21 typically developing children between 16 and 40 months were assessed repeatedly over two years to monitor their language development. The form allowed parents to document their children’s vocabulary development in both languages. Results showed that when knowledge of both languages was accounted for, the children acquired vocabulary at rates similar to those of monolingual speakers and used translational equivalents relatively early in language development. The study also showed that parents of bilingual children could accurately identify and differentiate language development in both of the child’s languages. Recommendations for adapting and using parent report instruments in bilingual language acquisition contexts are outlined.