MicroRNAs as biomarkers of brain injury in neonatal encephalopathy: an observational cohort study

Abstract Neonatal Encephalopathy (NE) is a major cause of lifelong disability and neurological complications in affected infants. Identifying novel diagnostic biomarkers in this population may assist in predicting MRI injury and differentiate neonates with NE from those with low-cord pH or healthy n...

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Main Authors: Fatima Dakroub, Firas Kobeissy, Stefania Mondello, Zhihui Yang, Haiyan Xu, Livia Sura, Candace Rossignol, Mehmet Albayram, Dhanashree Rajderkar, Kevin Wang, Michael D. Weiss
Format: Article
Language:English
Published: Nature Portfolio 2024-03-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-024-57166-z
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author Fatima Dakroub
Firas Kobeissy
Stefania Mondello
Zhihui Yang
Haiyan Xu
Livia Sura
Candace Rossignol
Mehmet Albayram
Dhanashree Rajderkar
Kevin Wang
Michael D. Weiss
author_facet Fatima Dakroub
Firas Kobeissy
Stefania Mondello
Zhihui Yang
Haiyan Xu
Livia Sura
Candace Rossignol
Mehmet Albayram
Dhanashree Rajderkar
Kevin Wang
Michael D. Weiss
author_sort Fatima Dakroub
collection DOAJ
description Abstract Neonatal Encephalopathy (NE) is a major cause of lifelong disability and neurological complications in affected infants. Identifying novel diagnostic biomarkers in this population may assist in predicting MRI injury and differentiate neonates with NE from those with low-cord pH or healthy neonates and may help clinicians make real-time decisions. To compare the microRNA (miRNA) profiles between neonates with NE, healthy controls, and neonates with low cord pH. Moreover, miRNA concentrations were compared to brain injury severity in neonates with NE. This is a retrospective analysis of miRNA profiles from select samples in the biorepository and data registry at the University of Florida Health Gainesville. The Firefly miRNA assay was used to screen a total of 65 neurological miRNA targets in neonates with NE (n = 36), low cord pH (n = 18) and healthy controls (n = 37). Multivariate statistical techniques, including principal component analysis and orthogonal partial least squares discriminant analysis, and miRNA Enrichment Analysis and Annotation were used to identify miRNA markers and their pathobiological relevance. A set of 10 highly influential miRNAs were identified, which were significantly upregulated in the NE group compared to healthy controls. Of these, miR-323a-3p and mir-30e-5p displayed the highest fold change in expression levels. Moreover, miR-34c-5p, miR-491-5p, and miR-346 were significantly higher in the NE group compared to the low cord pH group. Furthermore, several miRNAs were identified that can differentiate between no/mild and moderate/severe injury in the NE group as measured by MRI. MiRNAs represent promising diagnostic and prognostic tools for improving the management of NE.
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spelling doaj-art-6e4fd04e4f6e49f48e51105eef83c8a32025-08-20T02:16:34ZengNature PortfolioScientific Reports2045-23222024-03-0114111210.1038/s41598-024-57166-zMicroRNAs as biomarkers of brain injury in neonatal encephalopathy: an observational cohort studyFatima Dakroub0Firas Kobeissy1Stefania Mondello2Zhihui Yang3Haiyan Xu4Livia Sura5Candace Rossignol6Mehmet Albayram7Dhanashree Rajderkar8Kevin Wang9Michael D. Weiss10Department of Experimental Pathology, Immunology and Microbiology, Center for Infectious Diseases Research, American University of BeirutCenter for Neurotrauma, MultiOmics and Biomarkers, Department of Neurobiology, Morehouse School of MedicineDepartment of Biomedical and Dental Sciences and Morphofunctional Imaging, University of MessinaDepartment of Emergency Medicine, University of FloridaDepartment of Emergency Medicine, University of FloridaDepartment of Pediatrics, University of FloridaDepartment of Pediatrics, University of FloridaDepartment of Radiology, University of FloridaDepartment of Radiology, University of FloridaCenter for Neurotrauma, MultiOmics and Biomarkers, Department of Neurobiology, Morehouse School of MedicineDepartment of Pediatrics, University of FloridaAbstract Neonatal Encephalopathy (NE) is a major cause of lifelong disability and neurological complications in affected infants. Identifying novel diagnostic biomarkers in this population may assist in predicting MRI injury and differentiate neonates with NE from those with low-cord pH or healthy neonates and may help clinicians make real-time decisions. To compare the microRNA (miRNA) profiles between neonates with NE, healthy controls, and neonates with low cord pH. Moreover, miRNA concentrations were compared to brain injury severity in neonates with NE. This is a retrospective analysis of miRNA profiles from select samples in the biorepository and data registry at the University of Florida Health Gainesville. The Firefly miRNA assay was used to screen a total of 65 neurological miRNA targets in neonates with NE (n = 36), low cord pH (n = 18) and healthy controls (n = 37). Multivariate statistical techniques, including principal component analysis and orthogonal partial least squares discriminant analysis, and miRNA Enrichment Analysis and Annotation were used to identify miRNA markers and their pathobiological relevance. A set of 10 highly influential miRNAs were identified, which were significantly upregulated in the NE group compared to healthy controls. Of these, miR-323a-3p and mir-30e-5p displayed the highest fold change in expression levels. Moreover, miR-34c-5p, miR-491-5p, and miR-346 were significantly higher in the NE group compared to the low cord pH group. Furthermore, several miRNAs were identified that can differentiate between no/mild and moderate/severe injury in the NE group as measured by MRI. MiRNAs represent promising diagnostic and prognostic tools for improving the management of NE.https://doi.org/10.1038/s41598-024-57166-zNeonatal encephalopathyHIEMicroRNA biomarkers
spellingShingle Fatima Dakroub
Firas Kobeissy
Stefania Mondello
Zhihui Yang
Haiyan Xu
Livia Sura
Candace Rossignol
Mehmet Albayram
Dhanashree Rajderkar
Kevin Wang
Michael D. Weiss
MicroRNAs as biomarkers of brain injury in neonatal encephalopathy: an observational cohort study
Scientific Reports
Neonatal encephalopathy
HIE
MicroRNA biomarkers
title MicroRNAs as biomarkers of brain injury in neonatal encephalopathy: an observational cohort study
title_full MicroRNAs as biomarkers of brain injury in neonatal encephalopathy: an observational cohort study
title_fullStr MicroRNAs as biomarkers of brain injury in neonatal encephalopathy: an observational cohort study
title_full_unstemmed MicroRNAs as biomarkers of brain injury in neonatal encephalopathy: an observational cohort study
title_short MicroRNAs as biomarkers of brain injury in neonatal encephalopathy: an observational cohort study
title_sort micrornas as biomarkers of brain injury in neonatal encephalopathy an observational cohort study
topic Neonatal encephalopathy
HIE
MicroRNA biomarkers
url https://doi.org/10.1038/s41598-024-57166-z
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