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

Autores de IIS La Fe

• Jose David Piñeiro Ramos

  Autor

• Antonio Guillermo Núñez Ramiro

  Autor

• Roberto Llorens Salvador

  Autor

• Anna Parra Llorca

  Autor

• Ángel Sánchez Illana

  Autor

• Guillermo Quintas Soriano

  Autor

• Nuria Boronat González

  Autor

• Juan Martínez Rodilla

  Autor

• Julia Kuligowski

  Autor

• Máximo Vento Torres

  Autor

Grupos

• Investigacion Biomédica en Imagen (GIBI 2-30)

• Perinatología

Abstract

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.

Keywords

• liquid chromatography-time-of-flight mass spectrometry (LC-TOFMS); neonatal brain injury; perinatal asphyxia; untargeted metabolomics