Neonatal encephalopathy plasma metabolites are associated with neurodevelopmental outcomes
| العنوان: | Neonatal encephalopathy plasma metabolites are associated with neurodevelopmental outcomes |
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| المؤلفون: | Frances J. Northington, Jie Zhu, Marie Slevin, Gregory Ellis, Barbara D Friedes, Eleanor J. Molloy, Veronica Donoghue, David R. Graham, Cedric Manlhiot, Allen D. Everett, Lynne Kelly, Tammy Strickland, Mary O'Dea, Deirdre Sweetman, Robert Harlan, Aurelie Roux |
| المصدر: | Pediatric Research. 92:466-473 |
| بيانات النشر: | Springer Science and Business Media LLC, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Metabolite, Disease, Arginine, Bioinformatics, Bayley Scales of Infant Development, Infant, Newborn, Diseases, chemistry.chemical_compound, Metabolomics, RNA, Transfer, Tandem Mass Spectrometry, medicine, Humans, Histidine, KEGG, Neonatal encephalopathy, business.industry, Infant, Newborn, Infant, medicine.disease, Betaine, Metabolic pathway, chemistry, Brain Injuries, Pediatrics, Perinatology and Child Health, Gestation, Sugars, business |
| الوصف: | Background To investigate mechanisms of injury and recovery in neonatal encephalopathy (NE), we performed targeted metabolomic analysis of plasma using liquid chromatography with tandem mass spectrometry (LC/MS/MS) from healthy term neonates or neonates with NE. Methods Plasma samples from the NE (n = 45, day of life 0-1) or healthy neonatal (n = 30, ≥36 weeks gestation) cohorts had LC/MS/MS metabolomic profiling with a 193-plex targeted metabolite assay covering >366 metabolic pathways. Metabolite levels were compared to 2-year neurodevelopmental outcomes measured by the Bayley Scales of Infant and Toddler Development III (Bayley-III). Results Out of 193 metabolites, 57 met the pre-defined quality control criteria for analysis. Significant (after false discovery rate correction) KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways included aminoacyl-tRNA biosynthesis, arginine biosynthesis, and metabolism of multiple amino acids. Significant disease pathways included seizures. In regression models, histidine and C6 sugar amine were significantly associated with cognitive, motor, and language and betaine with cognitive and motor Bayley-III composite scores. The addition of histidine, C6 sugar amine, and betaine to a Sarnat score-based clinical regression model significantly improved model performance (Akaike information criterion and adjusted r2) for Bayley-III cognitive, motor, and language scores. Conclusions Plasma metabolites may help to predict neurological outcomes in neonatal brain injury and enhance current clinical predictors. Impact Plasma metabolites may help to predict neurological outcomes in NE and supplement current clinical predictors. Current metabolomics research is limited in terms of clinical application and association with long-term outcomes. Our study presents novel associations of plasma metabolites from the first 24 h of life and 2-year neurodevelopmental outcomes for infants with NE. Our metabolomics discovery provides insight into possible disease mechanisms and methods to rescue and/or supplement metabolic pathways involved in NE. Our metabolomics discovery of metabolic pathway supplementations and/or rescue mechanisms may serve as adjunctive therapies for NE. |
| تدمد: | 1530-0447 0031-3998 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1148646c4e4ee08d137798c9692f5b24 https://doi.org/10.1038/s41390-021-01741-x |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....1148646c4e4ee08d137798c9692f5b24 |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 15300447 00313998 |
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