Metabolic Phenotypes of Hypoxic-Ischemic Encephalopathy with Normal vs. Pathologic Magnetic Resonance Imaging Outcomes

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...

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Main Authors: José David Piñeiro-Ramos, Antonio Núñez-Ramiro, Roberto Llorens-Salvador, Anna Parra-Llorca, Ángel Sánchez-Illana, Guillermo Quintás, Nuria Boronat-González, Juan Martínez-Rodilla, Julia Kuligowski, Máximo Vento, The HYPOTOP Study Group
Format: Article
Language:English
Published: MDPI AG 2020-03-01
Series:Metabolites
Subjects:
Online Access:https://www.mdpi.com/2218-1989/10/3/109
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author José David Piñeiro-Ramos
Antonio Núñez-Ramiro
Roberto Llorens-Salvador
Anna Parra-Llorca
Ángel Sánchez-Illana
Guillermo Quintás
Nuria Boronat-González
Juan Martínez-Rodilla
Julia Kuligowski
Máximo Vento
The HYPOTOP Study Group
author_facet José David Piñeiro-Ramos
Antonio Núñez-Ramiro
Roberto Llorens-Salvador
Anna Parra-Llorca
Ángel Sánchez-Illana
Guillermo Quintás
Nuria Boronat-González
Juan Martínez-Rodilla
Julia Kuligowski
Máximo Vento
The HYPOTOP Study Group
author_sort José David Piñeiro-Ramos
collection DOAJ
description 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.
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spelling doaj.art-9b4324da2c104d75a1469520cb1a2a332022-12-22T03:20:56ZengMDPI AGMetabolites2218-19892020-03-0110310910.3390/metabo10030109metabo10030109Metabolic Phenotypes of Hypoxic-Ischemic Encephalopathy with Normal vs. Pathologic Magnetic Resonance Imaging OutcomesJosé David Piñeiro-Ramos0Antonio Núñez-Ramiro1Roberto Llorens-Salvador2Anna Parra-Llorca3Ángel Sánchez-Illana4Guillermo Quintás5Nuria Boronat-González6Juan Martínez-Rodilla7Julia Kuligowski8Máximo Vento9The HYPOTOP Study Group10Neonatal Research Group, Health Research Institute Hospital La Fe, Avenida Fernando Abril Martorell 106, 46026 Valencia, SpainDivision of Neonatology, University &amp; Polytechnic Hospital La Fe, Avenida Fernando Abril Martorell 106, 46026 Valencia, SpainDivision of Radiology and Imaging, University &amp; Polytechnic Hospital La Fe, Avenida Fernando Abril Martorell 106, 46026 Valencia, SpainNeonatal Research Group, Health Research Institute Hospital La Fe, Avenida Fernando Abril Martorell 106, 46026 Valencia, SpainNeonatal Research Group, Health Research Institute Hospital La Fe, Avenida Fernando Abril Martorell 106, 46026 Valencia, SpainHealth &amp; Biomedicine Unit, Leitat Technological Center, Parc Cientific Barcelona, 08028 Barcelona, SpainDivision of Neonatology, University &amp; Polytechnic Hospital La Fe, Avenida Fernando Abril Martorell 106, 46026 Valencia, SpainNeonatal Research Group, Health Research Institute Hospital La Fe, Avenida Fernando Abril Martorell 106, 46026 Valencia, SpainNeonatal Research Group, Health Research Institute Hospital La Fe, Avenida Fernando Abril Martorell 106, 46026 Valencia, SpainNeonatal Research Group, Health Research Institute Hospital La Fe, Avenida Fernando Abril Martorell 106, 46026 Valencia, SpainThe members of the HYPOTOP study group are listed in <sup>Appendix A</sup>.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&#8722;mass spectrometry method for the determination of lactate and pyruvate and an untargeted liquid chromatography&#8722;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.https://www.mdpi.com/2218-1989/10/3/109liquid chromatography–time-of-flight mass spectrometry (lc-tofms)neonatal brain injuryperinatal asphyxiauntargeted metabolomics
spellingShingle José David Piñeiro-Ramos
Antonio Núñez-Ramiro
Roberto Llorens-Salvador
Anna Parra-Llorca
Ángel Sánchez-Illana
Guillermo Quintás
Nuria Boronat-González
Juan Martínez-Rodilla
Julia Kuligowski
Máximo Vento
The HYPOTOP Study Group
Metabolic Phenotypes of Hypoxic-Ischemic Encephalopathy with Normal vs. Pathologic Magnetic Resonance Imaging Outcomes
Metabolites
liquid chromatography–time-of-flight mass spectrometry (lc-tofms)
neonatal brain injury
perinatal asphyxia
untargeted metabolomics
title Metabolic Phenotypes of Hypoxic-Ischemic Encephalopathy with Normal vs. Pathologic Magnetic Resonance Imaging Outcomes
title_full Metabolic Phenotypes of Hypoxic-Ischemic Encephalopathy with Normal vs. Pathologic Magnetic Resonance Imaging Outcomes
title_fullStr Metabolic Phenotypes of Hypoxic-Ischemic Encephalopathy with Normal vs. Pathologic Magnetic Resonance Imaging Outcomes
title_full_unstemmed Metabolic Phenotypes of Hypoxic-Ischemic Encephalopathy with Normal vs. Pathologic Magnetic Resonance Imaging Outcomes
title_short Metabolic Phenotypes of Hypoxic-Ischemic Encephalopathy with Normal vs. Pathologic Magnetic Resonance Imaging Outcomes
title_sort metabolic phenotypes of hypoxic ischemic encephalopathy with normal vs pathologic magnetic resonance imaging outcomes
topic liquid chromatography–time-of-flight mass spectrometry (lc-tofms)
neonatal brain injury
perinatal asphyxia
untargeted metabolomics
url https://www.mdpi.com/2218-1989/10/3/109
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