ORCID Profile
0000-0003-4665-6884
Current Organisation
Cork University Maternity Hospital
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Publisher: American Chemical Society (ACS)
Date: 21-08-2013
DOI: 10.1021/PR400617M
Abstract: Neonatal hypoxic ischemic encephalopathy (HIE) is a severe consequence of perinatal asphyxia (PA) that can result in life-long neurological disability. Disease mechanisms, including the role and interaction of in idual metabolic pathways, remain unclear. As hypoxia is an acute condition, aerobic energy metabolism is central to global metabolic pathways, and these metabolites are detectable using 1H NMR spectroscopy, we hypothesized that characterizing the NMR-derived umbilical cord serum metabolome would offer insight into the consequences of PA that lead to HIE. Fifty-nine at-risk infants were enrolled, together with 1:1 matched healthy controls, and stratified by disease severity (n=25, HIE n=34, non-HIE PA). Eighteen of 37 reproducibly detectable metabolites were significantly altered between study groups. Acetone, 3-hydroxybutyrate, succinate, and glycerol were significantly differentially altered in severe HIE. Multivariate data analysis revealed a metabolite profile associated with both asphyxia and HIE. Multiple-linear regression modeling using 4 metabolites (3-hydroxybutyrate, glycerol, O-phosphocholine, and succinate) predicted HIE severity with an adjusted R2 of 0.4. Altered ketones suggest that systemic metabolism may play a critical role in preventing neurological injury, while altered succinate provides a possible explanation for hypoxia-inducible factor 1-α (HIF-1α) stabilization in HI injury.
Publisher: Public Library of Science (PLoS)
Date: 05-12-2012
Publisher: SAGE Publications
Date: 25-08-2017
Abstract: Elucidating metabolic effects of hypoxic-ischaemic encephalopathy (HIE) may reveal early biomarkers of injury and new treatment targets. This study uses untargeted metabolomics to examine early metabolic alterations in a carefully defined neonatal population. Infants with perinatal asphyxia who were resuscitated at birth and recovered (PA group), those who developed HIE (HIE group) and healthy controls were all recruited at birth. Metabolomic analysis of cord blood was performed using direct infusion FT-ICR mass spectrometry. For each reproducibly detected metabolic feature, mean fold differences were calculated HIE vs. controls (ΔHIE) and PA vs. controls (ΔPA). Putative metabolite annotations were assigned and pathway analysis was performed. Twenty-nine putatively annotated metabolic features were significantly different in ΔPA after false discovery correction ( q 0.05), with eight of these also significantly altered in ΔHIE. Altered putative metabolites included melatonin, leucine, kynurenine and 3-hydroxydodecanoic acid which differentiated between infant groups (ΔPA and ΔHIE) and D-erythrose-phosphate, acetone, 3-oxotetradecanoic acid and methylglutarylcarnitine which differentiated across severity grades of HIE. Pathway analysis revealed ΔHIE was associated with a 50% and 75% perturbation of tryptophan and pyrimidine metabolism, respectively. We have identified perturbed metabolic pathways and potential biomarkers specific to PA and HIE, which measured at birth, may help direct treatment.
Publisher: Elsevier BV
Date: 05-2015
DOI: 10.1016/J.CLINBIOCHEM.2015.02.004
Abstract: Metabolomics is defined as the comprehensive study of all low molecular weight biochemicals, (metabolites) present in an organism. Using a systems biology approach, metabolomics in umbilical cord blood (UCB) may offer insight into many perinatal disease processes by uniquely detecting rapid biochemical pathway alterations. In vitro haemolysis is a common technical problem affecting UCB s ling in the delivery room, and can h er metabolomic analysis. The extent of metabolomic alteration which occurs in haemolysed s les is unknown. Visual haemolysis was designated by the laboratory technician using a standardised haemolysis index colour chart. The metabolomic profile of haemolysed and non-haemolysed UCB serum s les from 69 healthy term infants was compared using both (1)H-NMR and targeted DI and LC-MS/MS approach. We identified 43 metabolites that are significantly altered in visually haemolysed UCB s les, acylcarnitines (n=2), glycerophospholipids (n=23), sphingolipids (n=7), sugars (n=3), amino acids (n=4) and Krebs cycle intermediates (n=4). This information will be useful for researchers in the field of neonatal metabolomics to avoid false findings in the presence of haemolysis, to ensure reproducible and credible results.
Publisher: S. Karger AG
Date: 2016
DOI: 10.1159/000446556
Abstract: b i Background: /i /b A sup /sup H-NMR-derived metabolomic index based on early umbilical cord blood alterations of succinate, glycerol, 3-hydroxybutyrate and O-phosphocholine has shown potential for the prediction of hypoxic-ischaemic encephalopathy (HIE) severity. b i Objective: /i /b To evaluate whether this metabolite score can predict 3-year neurodevelopmental outcome in infants with perinatal asphyxia and HIE, compared with current standard biochemical and clinical markers. b i Methods: /i /b From September 2009 to June 2011, infants at risk of perinatal asphyxia were recruited from a single maternity hospital. Cord blood was drawn and biobanked at delivery. Neonates were monitored for development of encephalopathy both clinically and electrographically. Neurodevelopmental outcome was assessed at 36-42 months using the Bayley Scales of Infant and Toddler Development, ed. III (BSID-III). Death and cerebral palsy were also considered as abnormal end points. b i Results: /i /b Thirty-one infants had both metabolomic analysis and neurodevelopmental outcome at 36-42 months. No child had a severely abnormal BSID-III result. The metabolite index significantly correlated with outcome (& #x03C1 sup /sup = 0.30, p 0.01), which is robust to predict both severe outcome (area under the receiver operating characteristic curve: 0.92, p i /i .01) and intact survival (0.80, p = 0.01). There was no correlation between the index score and performance in the in idual BSID-III subscales (cognitive, language, motor). b i Conclusions: /i /b The metabolite index outperformed other standard biochemical markers at birth for prediction of outcome at 3 years, but was not superior to EEG or the Sarnat score.
No related grants have been discovered for Brian Walsh.