Abstract
Hypoxic-Ischemic Encephalopathy (HIE) is one of the most relevant contributors to neurological disability in term infants. We hypothesized that clinical outcomes of newborns with (HIE) can be associated with changes at plasma metabolic level enabling the detection of brain injury. Plasma samples of a cohort of 55 asphyxiated infants who evolved to moderate/severe HIE were collected between birth and completion of therapeutic hypothermia (TH). Samples were analyzed employing a quantitative gas chromatography–mass spectrometry method for the determination of lactate and pyruvate and an untargeted liquid chromatography–time-of-flight mass spectrometry method for metabolic fingerprinting. Brain injury was assessed employing magnetic resonance imaging (MRI). A critical assessment of the usefulness of lactate, pyruvate, and pyruvate/lactate for outcome prediction was carried out. Besides, metabolic fingerprinting identified a dynamic perturbation of eleven metabolic pathways, including amino acid and purine metabolism, and the steroid hormone biosynthesis, in newborns with pathologic MRI outcomes. Although data suggest the usefulness of lactate and pyruvate monitoring during 72 h for discerning outcomes, only the steroid hormone biosynthesis pathway was significantly altered in early plasma samples (i.e., before the initiation of TH). This study highlights pathways that might potentially be targeted for biomarker discovery or adjuvant therapies to be combined with TH.
Highlights
Hypoxic-Ischemic Encephalopathy (HIE) is the neurological consequence of impaired blood flow and/or gas exchange during birth [1]
For the quantitative determination of lactate and pyruvate, a targeted gas chromatography–mass spectrometry (GC-MS) method was used, whereas untargeted fingerprinting was carried out using LC-TOFMS
The difference in concentration levels of lactate between newborns with normal and pathologic magnetic resonance imaging (MRI) outcomes decreased over time, whereas an increase was noted for pyruvate concentrations
Summary
Hypoxic-Ischemic Encephalopathy (HIE) is the neurological consequence of impaired blood flow and/or gas exchange during birth [1]. Decreased cerebral perfusion and oxygenation trigger a sequence of acute cerebral metabolic alterations that characterize the primary energy failure phase of HIE. The process undergoes a latent phase that lasts up to 6 h. This stage is followed by a secondary energy failure phase that enhances cerebral injury and may last for days, weeks, or even months [2]. HIE is one of the most relevant contributors to neurological disability in the pediatric age. In high-income countries, the incidence of HIE is around 1.6 per 1000 infants, while the risk is around
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