Blood Plasma Metabolic Profile of Newborns with Hypoxic-Ischaemic Encephalopathy by GC-MS

Abstract

Background. Early diagnosis of hypoxic-ischaemic encephalopathy (HIE) is crucial in preventing neurodevelopmental disabilities and reducing morbidity and mortality. The study was to investigate the plasma metabolic signatures in the peripheral blood of HIE newborns and explore the potential diagnostic biomarkers. Method. In the present study, 24 newborns with HIE and 24 healthy controls were recruited. The plasma metabolites were measured by gas chromatography-mass spectrometry (GC-MS), and the raw data was standardized by the EigenMS method. Significantly differential metabolites were identified by multivariate statistics. Pathway enrichment was performed by bioinformatics analysis. Meanwhile, the diagnostic value of candidate biomarkers was evaluated. Result. The multivariate statistical models showed a robust capacity to distinguish the HIE cases from the controls. 52 metabolites were completely annotated. 331 significantly changed pathways were enriched based on seven databases, including 33 overlapped pathways. Most of them were related to amino acid metabolism, energy metabolism, neurotransmitter biosynthesis, pyrimidine metabolism, the regulation of HIF by oxygen, and GPCR downstream signaling. 14 candidate metabolites showed great diagnostic potential on HIE. Among them, alpha-ketoglutaric acid has the potential to assess the severity of HIE in particular. Conclusion. The blood plasma metabolic profile could comprehensively reflect the metabolic disorders of the whole body under hypoxia-ischaemic injury. Several candidate metabolites may serve as promising biomarkers for the early diagnosis of HIE. Further validation based on large clinical samples and the establishment of guidelines for the clinical application of mass spectrometry data standardization methods are imperative in the future.

Metabolite Biomarkers for Early Ischemic–Hypoxic Encephalopathy: An Experimental Study Using the NeoBase 2 MSMS Kit in a Rat Model

“…In addition, hypoxia/ischemia leads to a metabolic shift toward anaerobic metabolic pathways, disabling the Krebs cycle and leading to an accumulation of cycle intermediates and byproducts of pyruvate metabolism, potentially increasing the concentrations of precursor amino acids identified in our study. The role of amino acids as biomarkers for early HIE has previously been demonstrated in both model experiments and clinical studies [15,44,[60][61][62]. Furthermore, these amino acids could serve as alternative energy substrates for the neonatal brain and muscles under hypoxic conditions [63].…”

“…However, modern methods of assessing the risk of brain injury in neonates have limitations associated with the first hours of life, and uncertainty about the severity of progressive brain injury and potential neurological consequences remains at this early stage [14]. For the early differential diagnosis of HIE in newborns, approaches to analyze metabolic changes in the blood of newborns using new analytical methods, in particular gas chromatography-mass spectrometry, may be suitable [15]. This method allows the identification of hundreds of metabolites within a few hours.…”

Metabolite Biomarkers for Early Ischemic Hypoxic Encephalopathy: An Experimental Study Using the NeoBase 2 MSMS Kit in a Rat Model

“…In addition, hypoxia/ischemia leads to a metabolic shift toward anaerobic metabolic pathways, disabling the Krebs cycle and leading to an accumulation of cycle intermediates and byproducts of pyruvate metabolism, potentially increasing the concentrations of precursor amino acids identified in our study. The role of amino acids as biomarkers for early HIE has previously been demonstrated in both model experiments and clinical studies [17,46,[62][63][64]. Furthermore, these amino acids could serve as alternative energy substrates for the neonatal brain and muscles under hypoxic conditions [65].…”

“…[16] For an early differential diagnosis of HIE in newborns, approaches to analyze metabolic changes in the blood of newborns using new analytical methods, in particular chromatography-mass spectrometry, might be suitable. [17]This method allows the identification of hundreds of metabolites within a few hours, which fits into the time frame necessary to obtain analytical results and make decisions on treatment strategies. Clinical studies during the neonatal period are very scarce.…”