Identifying Hypoxia in a Newborn Piglet Model Using Urinary NMR Metabolomic Profiling

Abstract

Establishing the severity of hypoxic insult during the delivery of a neonate is key step in the determining the type of therapy administered. While successful therapy is present, current methods for assessing hypoxic injuries in the neonate are limited. Urine Nuclear Magnetic Resonance (NMR) metabolomics allows for the rapid non-invasive assessment of a multitude breakdown products of physiological processes. In a newborn piglet model of hypoxia, we used NMR spectroscopy to determine the levels of metabolites in urine samples, which were correlated with physiological measurements. Using PLS-DA analysis, we identified 13 urinary metabolites that differentiated hypoxic versus nonhypoxic animals (1-methylnicotinamide, 2-oxoglutarate, alanine, asparagine, betaine, citrate, creatine, fumarate, hippurate, lactate, N-acetylglycine, N-carbamoyl-β-alanine, and valine). Using this metabolomic profile, we then were able to blindly identify hypoxic animals correctly 84% of the time compared to nonhypoxic controls. This was better than using physiologic measures alone. Metabolomic profiling of urine has potential for identifying neonates that have undergone episodes of hypoxia.

Proton nuclear magnetic resonance spectroscopy of urine samples in preterm asphyctic newborn: A metabolomic approach

“…From literature we know that some metabolites identified into the urines of our asphyxiated infants can be attributed to the biochemical changes happened into the body in reaction to hypoxia [1,27,40].…”

“…Currently animal models of neonatal hypoxia offer precise physiological measurements that can be directly compared to acute changes in the urine metabolome in order to establish a model of neonatal hypoxic injury [39]. Other studies used NMR metabolomics in a newborn piglet model, in conjunction with physiological measurements, to establish a metabolomic profile of neonatal hypoxiareoxygenation [40] for identifying the unknown biological pathways that lead to cardiac arrest [41]. In this study, by using NMR metabolomic approach, the urine of asphyctic together with control group neonates was analyzed.…”

Metabolic adaptation and neuroprotection differ in the retina and choroid in a piglet model of acute postnatal hypoxia

“…Despite our model being one of hypoxia, a drastic drop in mean arterial blood pressure to 20 mmHg supports the idea of an ensuing metabolic ischemia. In similar experimental conditions, piglets challenged with hypoxia alone experience a marked reduction in cardiac output, which parallels a drop in pH, oxygenation and mean arterial blood pressure (24). Thus, it is reasonable to assume that our model has features of both hypoxia and ischemia, a physiological condition that can contribute to a blunted stabilization of HIF-1α (23).…”

Preliminary case control study to establish the correlation between novel peroxidation biomarkers in cord serum and the severity of hypoxic ischemic encephalopathy

“…Therefore, the reliability of the analysis of cord blood gases is of limited value in predicting HIE [5][6][7]. Moreover, the clinical methods employed to assess HIE which include Apgar score, amplitude integrated electroencephalography, and magnetic resonance imaging are useful for predicting some outcome of neonatal hypoxia but lack the sensitivity needed to implement effective therapies such as hypothermia [8].…”