Dataset Information

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

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.

SUBMITTER: Pineiro-Ramos JD

PROVIDER: S-EPMC7143850 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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

Piñeiro-Ramos José David JD Núñez-Ramiro Antonio A Llorens-Salvador Roberto R Parra-Llorca Anna A Sánchez-Illana Ángel Á Quintás Guillermo G Boronat-González Nuria N Martínez-Rodilla Juan J Kuligowski Julia J Vento Máximo M The Hypotop Study Group

Metabolites 20200314 3

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 ch ...[more]

PMID: 32183365

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Project description:Background: Hypoxic-ischemic encephalopathy (HIE) is a major contributor to child mortality and morbidity. Reliable prognostication for HIE is of key importance. Proton magnetic resonance spectroscopy (1H-MRS) is a quantitative, non-invasive method that has been demonstrated to be a suitable complementary tool for prediction. The aim of this study was to investigate the prognostic capability of 1H-MRS in the era of therapeutic hypothermia (TH). Methods: Databases, namely MEDLINE, Embase, Web of Science, and the Cochrane library (Cochrane Center Register of Controlled Trials), were searched for studies published before July 17, 2017. Study selection and data extraction were performed by two independent reviewers. The mean difference (MD) or standardized MD (SMD) and 95% confidence interval (CI) were calculated using random-effects models. Subgroup analyses were conducted based on the use of TH. Results: Among the 1,150 relevant studies, seven were included for meta-analysis, but only two small studies were conducted under TH. For 1H-MRS measurement, three peak area ratios revealed predictive values for adverse outcomes in TH subgroup and the combined results (with and without TH): N-acetylaspartate (NAA)/creatine in basal ganglia/thalamus (BG/T) in TH (MD -0.31, 95%CI -0.55 to -0.07) and combined results (MD -0.37, 95% CI -0.49 to -0.25); NAA/choline in BG/T in TH (MD -0.89, 95%CI -1.43 to -0.35) and combined results (MD -0.25, 95%CI -0.42 to -0.07); and myo-inositol/choline in cerebral cortex in TH (MD -1.94, 95%CI -3.69 to -0.19) and combined results (MD -1.64, 95%CI -2.64 to -0.64). Moreover, NAA relative concentration is associated with adverse outcomes: in TH (MD -0.04, 95%CI -0.06 to -0.02) and combined results (MD -0.06, 95%CI -0.11 to -0.01) in white matter; in TH (MD -0.04, 95%CI -0.07 to -0.01) and combined results (MD -0.05, 95%CI -0.07 to -0.02) in gray matter. Conclusions: NAA may be a potential marker in outcome prediction for all HIE subjects. It seems that MDs for the ratios including NAA are larger than for its relative concentration, and therefore are more likely to be measurable in a clinical context. Larger prospective multicenter studies with a standardized protocol for both measurement protocols and analysis methods are required in future studies.

Project description:ContextClinicians use brain magnetic resonance imaging (MRI) to discuss neurodevelopmental prognosis with parents of neonates with hypoxic-ischemic encephalopathy (HIE) treated with therapeutic hypothermia (TH).PurposeTo investigate how clinicians and parents discuss these MRI results in the context of HIE and TH and how these discussions could be facilitated and more meaningful for parents.ProceduresMixed-methods surveys with open-ended and closed-ended questions were completed by two independent groups. (1) Clinicians responded to clinical vignettes of neonates with HIE treated with TH with various types of clinical features, evolution and extent of brain injury and questions about how they discuss brain MRI results in this context. (2) Parents of children with HIE treated with TH responded to questions about the discussion of MRI that they had while still in the neonatal intensive care unit and were asked to place it in perspective with the outcomes of their child when he/she reached at least 2 years of age. Open-ended responses were analyzed using a thematic analysis approach. Closed-ended responses are presented descriptively.ResultsClinicians reported uncertainty, lack of confidence, and limitations when discussing brain MRI results in the context of HIE and TH. Brain MRI results were "usually" (53%) used in the prognostication discussion. When dealing with day-2 brain MRIs performed during TH, most clinicians (40%) assumed that the results of these early MRIs were only "sometimes" accurate and only used them "sometimes" (33%) to discuss prognosis; a majority of them (66%) would "always" repeat imaging at a later time-point to discuss prognosis. Parents also struggled with this uncertainty, but did not discuss limitations of MRI as often. Parents raised the importance of the setting where the discussion took place and the importance to inform them as quickly as possible. Clinicians identified strategies to improve these discussions, including interdisciplinary approach, formal training, and standardized approach to report brain MRI. Parents highlighted the importance of communication skills, the stress, the hope surrounding their situation, and the need to receive answers as soon as possible. The importance of showing the pictures or making representative drawing of the injury, but also highlighting the not-injured brain, was also highlighted by parents.ConclusionsDiscussing brain MRI results for neonates with HIE treated with TH are challenging tasks for clinicians and daunting moments for parents.

Dataset Information

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

Publications

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

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