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CURATOR
A pinboard by
Julia Kuligowski

Post-Doctoral Researcher, Health Research Institute La Fe

PINBOARD SUMMARY

Minimally invasive assessment of the degree of asphyxia in the fetal-to-neonatal transition

Hypoxic-ischemic encephalopathy (HIE) secondary to perinatal asphyxia is a leading cause of mortality and long-term neurologic co-morbidities in the term neonate. Moderate whole body hypothermia initiated within 6 hours from birth is the most successful intervention for treatment of moderate to severe HIE. This work strives for an early metabolic biomarker score for assessing the risk of developing moderate to severe HIE in order to provide an objective measure for aiding clinical decisions. From a consolidated piglet model for neonatal hypoxia-ischemia, plasma samples were withdrawn before and at different time points after a hypoxic insult. A set of three metabolites (choline, xanthine and hypoxanthine) showing maximum correlation with hypoxia time was identified from an untargeted liquid chromatography coupled to tandem mass spectrometry experiment and a multivariate Partial Least Squares metabolite score for predicting hypoxia time was established. Its performance as a biomarker for perinatal hypoxia was compared to lactate which is currently considered as the gold standard. The metabolite score performed similar to lactate for plasma samples withdrawn before and directly after a hypoxic insult, both providing sensitivity and specificity values equal to 1. However, in samples collected 2 h after resuscitation, lactate levels were not suitable for identifying asphyxiated piglets, while the metabolite score provided enhanced predictive capacity. Results evidenced the usefulness of the metabolite score for an early assessment of the severity of hypoxic insults based on serial determinations. Ongoing studies are testing its capacity for clinical diagnosis and patient stratification in multicenter trials involving newborns with HIE.

3 ITEMS PINNED

Plasma metabolite score correlates with Hypoxia time in a newly born piglet model for asphyxia.

Abstract: Hypoxic-ischemic encephalopathy (HIE) secondary to perinatal asphyxia is a leading cause of mortality and acquired long-term neurologic co-morbidities in the neonate. The most successful intervention for the treatment of moderate to severe HIE is moderate whole body hypothermia initiated within 6h from birth. The objective and prompt identification of infants who are at risk of developing moderate to severe HIE in the critical first hours still remains a challenge. This work proposes a metabolite score calculated based on the relative intensities of three metabolites (choline, 6,8-dihydroxypurine and hypoxanthine) that showed maximum correlation with hypoxia time in a consolidated piglet model for neonatal hypoxia-ischemia. The metabolite score's performance as a biomarker for perinatal hypoxia and its usefulness for clinical grading and decision making have been assessed and compared to the performance of lactate which is currently considered the gold standard. For plasma samples withdrawn before and directly after a hypoxic insult, the metabolite score performed similar to lactate. However, it provided an enhanced predictive capacity at 2h after resuscitation. The present study evidences the usefulness of the metabolite score for improving the early assessment of the severity of the hypoxic insult based on serial determinations in a minimally invasive biofluid. The applicability of the metabolite score for clinical diagnosis and patient stratification for hypothermia treatment has to be confirmed in multicenter trials involving newborns suffering from HIE.

Pub.: 18 Feb '17, Pinned: 19 Jun '17