Neonatal encephalopathy plasma metabolites are associated with neurodevelopmental outcomes.
Neonatal encephalopathy plasma metabolites are associated with neurodevelopmental outcomes.
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DOI：
10.1038/s41390-021-01741-x
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发表时间：
2022-08
影响因子：
3.6
通讯作者：
Everett AD
中科院分区：
文献类型：
--
作者：
Friedes BD;Molloy E;Strickland T;Zhu J;Slevin M;Donoghue V;Sweetman D;Kelly L;O'Dea M;Roux A;Harlan R;Ellis G;Manlhiot C;Graham D;Northington F;Everett AD
为了探讨新生儿脑病(NE)的损伤和康复机制，我们采用LC/MS/MS对正常足月新生儿和NE新生儿的血浆进行了靶向代谢组学分析。来自NE(n=45，出生0-1天)或健康新生儿(n=30，≥孕36周)的血浆样本进行了LC/MS/MS代谢组分析。将代谢物水平与贝利婴幼儿发育量表III(Bayley-III)测量的两年神经发育结果进行比较。有57/193个代谢物符合预先规定的分析质量控制标准。重要的(FDR校正后)KEGG途径包括氨酰-tRNA生物合成、精氨酸生物合成和多种氨基酸的代谢。重要的疾病途径包括癫痫发作。在回归模型中，组氨酸和C6糖胺与认知、运动和语言显著相关，甜菜碱与认知和运动Bayley-III综合得分显著相关。在基于Sarnat评分的临床回归模型中添加组氨酸、C6糖胺和甜菜碱显著改善了Bayley-III认知、运动和语言评分的模型性能(AIC和调整后的R2)。血浆代谢物可能有助于预测新生儿脑损伤的神经预后，并增强当前的临床预测指标。
To investigate mechanisms of injury and recovery in neonatal encephalopathy (NE), we performed targeted metabolomic analysis of plasma using LC/MS/MS from healthy term neonates or neonates with NE. 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 two-year neurodevelopmental outcomes measured by the Bayley Scales of Infant and Toddler Development III (Bayley-III). 57/193 metabolites met pre-defined quality control criteria for analysis. Significant (after FDR correction) KEGG 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. Addition of histidine, C6 sugar amine, and betaine to a Sarnat score based clinical regression model significantly improved model performance (AIC and adjusted r2) for Bayley-III cognitive, motor, and language scores. Plasma metabolites may help to predict neurological outcomes in neonatal brain injury and enhance current clinical predictors.
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影响因子：
4.2
作者：
Chitturi J;Li Y;Santhakumar V;Kannurpatti SS
通讯作者：
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通讯作者：
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