title: 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 For plasma samples withdrawn before and directly after a hypoxic insult, the metabolite score performed similar to lactate.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.
authors.affiliation: Neonatal Research Group, Health Research Institute Hospital La Fe, Avenida Fernando Abril Martorell 106, Valencia, Spain.
authors.forename: Julia
authors.initials: J
authors.lastname: Kuligowski
authors.affiliation: Department of Pediatric Research, Institute for Surgical Research, University of Oslo, Oslo University Hospital - Rikshospitalet, Oslo, Norway; Department of Pediatrics, Vestfold Hospital Trust, Tønsberg, Norway.
authors.forename: Rønnaug
authors.initials: R
authors.lastname: Solberg
authors.affiliation: Neonatal Research Group, Health Research Institute Hospital La Fe, Avenida Fernando Abril Martorell 106, Valencia, Spain.
authors.forename: Ángel
authors.initials: Á
authors.lastname: Sánchez-Illana
authors.affiliation: Department of Pediatric Research, Institute for Surgical Research, University of Oslo, Oslo University Hospital - Rikshospitalet, Oslo, Norway.
authors.forename: Leonid
authors.initials: L
authors.lastname: Pankratov
authors.affiliation: Neonatal Research Group, Health Research Institute Hospital La Fe, Avenida Fernando Abril Martorell 106, Valencia, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Parra-Llorca
authors.affiliation: Human & Environmental Health & Safety (HEHS), Leitat Technological Center, Avenida Fernando Abril Martorell 106, 46026 Valencia, Spain; Unidad Analítica, Health Research Institute La Fe, Avenida Fernando Abril Martorell 106, 46026 Valencia, Spain.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Quintás
authors.affiliation: Department of Pediatric Research, Institute for Surgical Research, University of Oslo, Oslo University Hospital - Rikshospitalet, Oslo, Norway.
authors.forename: Ola Didrik
authors.initials: OD
authors.lastname: Saugstad
authors.affiliation: Neonatal Research Group, Health Research Institute Hospital La Fe, Avenida Fernando Abril Martorell 106, Valencia, Spain; Division of Neonatology, University & Polytechnic Hospital La Fe, Avenida Fernando Abril Martorell 106, Valencia, Spain. Electronic address: maximo.vento@uv.es.
authors.forename: Máximo
authors.initials: M
authors.lastname: Vento
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001238:Asphyxia Neonatorum / Q000097:blood / Q000150:complications / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood; D002794:Choline / Q000097:blood*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D019271:Hypoxanthine / Q000097:blood*; D020925:Hypoxia-Ischemia, Brain / Q000175:diagnosis*; D008297:Male; D012720:Severity of Illness Index; D013552:Swine
chemical_list: D015415:Biomarkers; D019271:Hypoxanthine; D002794:Choline
keywords: Hypoxia; Liquid Chromatography – Time-of-Flight Mass Spectrometry (LC-TOF-MS); Metabolic biomarker; Neonatal piglet model; Newborn; Perinatal asphyxia