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A metabolomic-based biomarker discovery study for predicting phototherapy duration for neonatal hyperbilirubinemia

BACKGROUND: Phototherapy is a recommended method for the treatment of neonatal hyperbilirubinemia. However, biomarkers for predicting the more effective duration of phototherapy prior to treatment are lacking. Therefore, we aimed to determine novel predictors for the timing of phototherapy from the...

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Autores principales: Zhu, Danying, Wang, Mingjie, Zhang, Zhongxiao, Liu, Minghua, Liu, Yiwen, Wu, Weiling, Lu, Dian, Wu, Xiaoyun, Wu, Wei, Wang, Xingyun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AME Publishing Company 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9834951/
https://www.ncbi.nlm.nih.gov/pubmed/36643669
http://dx.doi.org/10.21037/tp-22-637
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author Zhu, Danying
Wang, Mingjie
Zhang, Zhongxiao
Liu, Minghua
Liu, Yiwen
Wu, Weiling
Lu, Dian
Wu, Xiaoyun
Wu, Wei
Wang, Xingyun
author_facet Zhu, Danying
Wang, Mingjie
Zhang, Zhongxiao
Liu, Minghua
Liu, Yiwen
Wu, Weiling
Lu, Dian
Wu, Xiaoyun
Wu, Wei
Wang, Xingyun
author_sort Zhu, Danying
collection PubMed
description BACKGROUND: Phototherapy is a recommended method for the treatment of neonatal hyperbilirubinemia. However, biomarkers for predicting the more effective duration of phototherapy prior to treatment are lacking. Therefore, we aimed to determine novel predictors for the timing of phototherapy from the perspective of metabolomics. METHODS: A total of 12 newborns with neonatal hyperbilirubinemia were recruited on the day of admission. The infants were divided into a short-duration (<30 hours) phototherapy group and a long-duration (≥30 hours) phototherapy group based on the length of phototherapy treatment. Metabolites in serum samples were then explored using an untargeted metabolomics strategy. RESULTS: In total, 59 of 1,073 significantly different metabolites were identified between the short-duration and long-duration phototherapy groups, including 18 upregulated and 41 downregulated metabolites. The results of metabolomic analysis showed that the differentially expressed metabolites were enriched in glycerophospholipid metabolism, which is closely associated with the excretion of bilirubin. Moreover, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the metabolites were also enriched in alpha-Linolenic acid metabolism and fatty acid elongation. Spearman correlation hierarchical clustering analysis demonstrated that 9 metabolites were negatively correlated with the duration of phototherapy. Metabolites, especially phosphatidylethanolamine (PE) (22:1(13Z)/15:0), phosphatidylcholine (PC) (18:1(9Z)/18:1(9Z)), phosphatidylserine (PS) (22:0/15:0), 5,6-dihydrouridine, and PE (MonoMe(11,3)/MonoMe(13,5)), had better predictability for the duration of phototherapy [area under curve (AUC): 1; 95% confidence interval (CI): 1–1] than total serum total bilirubin and direct bilirubin (AUC: 0.806; 95% CI: 0.55–1), as revealed by receiver operating characteristic analysis. CONCLUSIONS: Our research found that the differential metabolites were associated with the duration of neonatal jaundice and that glycerophospholipid metabolism might have played a role in this biological process. Moreover, metabolites such as PE (22:1(13Z)/15:0), PC (18:1(9Z)/18:1(9Z)), PS (22:0/15:0), 5,6-dihydrouridine, and PE (MonoMe(11,3)/MonoMe(13,5)) could be used as predictors for phototherapy duration in neonatal hyperbilirubinemia and assist with decision-making.
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spelling pubmed-98349512023-01-13 A metabolomic-based biomarker discovery study for predicting phototherapy duration for neonatal hyperbilirubinemia Zhu, Danying Wang, Mingjie Zhang, Zhongxiao Liu, Minghua Liu, Yiwen Wu, Weiling Lu, Dian Wu, Xiaoyun Wu, Wei Wang, Xingyun Transl Pediatr Original Article BACKGROUND: Phototherapy is a recommended method for the treatment of neonatal hyperbilirubinemia. However, biomarkers for predicting the more effective duration of phototherapy prior to treatment are lacking. Therefore, we aimed to determine novel predictors for the timing of phototherapy from the perspective of metabolomics. METHODS: A total of 12 newborns with neonatal hyperbilirubinemia were recruited on the day of admission. The infants were divided into a short-duration (<30 hours) phototherapy group and a long-duration (≥30 hours) phototherapy group based on the length of phototherapy treatment. Metabolites in serum samples were then explored using an untargeted metabolomics strategy. RESULTS: In total, 59 of 1,073 significantly different metabolites were identified between the short-duration and long-duration phototherapy groups, including 18 upregulated and 41 downregulated metabolites. The results of metabolomic analysis showed that the differentially expressed metabolites were enriched in glycerophospholipid metabolism, which is closely associated with the excretion of bilirubin. Moreover, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the metabolites were also enriched in alpha-Linolenic acid metabolism and fatty acid elongation. Spearman correlation hierarchical clustering analysis demonstrated that 9 metabolites were negatively correlated with the duration of phototherapy. Metabolites, especially phosphatidylethanolamine (PE) (22:1(13Z)/15:0), phosphatidylcholine (PC) (18:1(9Z)/18:1(9Z)), phosphatidylserine (PS) (22:0/15:0), 5,6-dihydrouridine, and PE (MonoMe(11,3)/MonoMe(13,5)), had better predictability for the duration of phototherapy [area under curve (AUC): 1; 95% confidence interval (CI): 1–1] than total serum total bilirubin and direct bilirubin (AUC: 0.806; 95% CI: 0.55–1), as revealed by receiver operating characteristic analysis. CONCLUSIONS: Our research found that the differential metabolites were associated with the duration of neonatal jaundice and that glycerophospholipid metabolism might have played a role in this biological process. Moreover, metabolites such as PE (22:1(13Z)/15:0), PC (18:1(9Z)/18:1(9Z)), PS (22:0/15:0), 5,6-dihydrouridine, and PE (MonoMe(11,3)/MonoMe(13,5)) could be used as predictors for phototherapy duration in neonatal hyperbilirubinemia and assist with decision-making. AME Publishing Company 2022-12 /pmc/articles/PMC9834951/ /pubmed/36643669 http://dx.doi.org/10.21037/tp-22-637 Text en 2022 Translational Pediatrics. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Original Article
Zhu, Danying
Wang, Mingjie
Zhang, Zhongxiao
Liu, Minghua
Liu, Yiwen
Wu, Weiling
Lu, Dian
Wu, Xiaoyun
Wu, Wei
Wang, Xingyun
A metabolomic-based biomarker discovery study for predicting phototherapy duration for neonatal hyperbilirubinemia
title A metabolomic-based biomarker discovery study for predicting phototherapy duration for neonatal hyperbilirubinemia
title_full A metabolomic-based biomarker discovery study for predicting phototherapy duration for neonatal hyperbilirubinemia
title_fullStr A metabolomic-based biomarker discovery study for predicting phototherapy duration for neonatal hyperbilirubinemia
title_full_unstemmed A metabolomic-based biomarker discovery study for predicting phototherapy duration for neonatal hyperbilirubinemia
title_short A metabolomic-based biomarker discovery study for predicting phototherapy duration for neonatal hyperbilirubinemia
title_sort metabolomic-based biomarker discovery study for predicting phototherapy duration for neonatal hyperbilirubinemia
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9834951/
https://www.ncbi.nlm.nih.gov/pubmed/36643669
http://dx.doi.org/10.21037/tp-22-637
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