Post-Doctoral Researcher, Health Research Institute La Fe
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 From a consolidated piglet model for neonatal hypoxia-ischemia, plasma samples were withdrawn before and at different time points after a hypoxic insult.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 The metabolite score performed similar to lactate for plasma samples withdrawn before and directly after a hypoxic insult, both providing sensitivity and specificity values equal to 1.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.
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
Abstract: Perinatal hypoxic–ischemic brain damage is a major cause of mortality and morbidity in the neonatal period. Currently, limited ranges of biochemical tests assessing the intensity and duration of hypoxia are ready for clinical use. However, the need to initiate hypothermia therapy early after the clinical suspicion of hypoxic–ischemic encephalopathy requires the availability of early and reliable hypoxia markers. We have sought these biomarkers in an experimental model of hypoxia reoxygenation.
Pub.: 07 Apr '16, Pinned: 19 Jun '17
Abstract: The prompt and reliable identification of infants at risk of hypoxic-ischemic encephalopathy secondary to perinatal asphyxia in the first critical hours is important for clinical decision-making and yet still remains a challenge. This work strives for the evaluation of a panel of metabolic biomarkers that have been associated with the hypoxic-ischemic insult in the perinatal period. Plasma and urine samples from a consolidated newborn piglet model of hypoxia and withdrawn before and at different time points after a hypoxic insult were analyzed and compared to a control group. Time-dependent metabolic biomarker profiles were studied and observed patterns were similar to those of lactate levels, which are currently considered the gold standard for assessing hypoxia. Class prediction performance could be improved by the use of a combination of the whole panel of determined metabolites in plasma as compared to lactate values. Using a multivariate model including lactate together with the studied metabolic biomarkers allowed to improve the prediction performance of duration of hypoxia time, which correlates with the degree of brain damage. The present study evidences the usefulness of choline and related metabolites for improving the early assessment of the severity of the hypoxic insult.
Pub.: 11 Jan '17, Pinned: 19 Jun '17