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宫内生长受限早产儿代谢组学特征:一项配对病例对照研究。

Metabolomic profiling of intrauterine growth-restricted preterm infants: a matched case-control study.

机构信息

Department of Women's and Children's Health, Neonatal Intensive Care Unit, University Hospital of Padua, Padua, Italy.

Institute of Pediatric Research, Città della Speranza, Laboratory of Mass Spectrometry and Metabolomics, Padua, Italy.

出版信息

Pediatr Res. 2023 May;93(6):1599-1608. doi: 10.1038/s41390-022-02292-5. Epub 2022 Sep 9.

DOI:10.1038/s41390-022-02292-5
PMID:36085367
Abstract

BACKGROUND

The biochemical variations occurring in intrauterine growth restriction (IUGR), when a fetus is unable to achieve its genetically determined potential, are not fully understood. The aim of this study is to compare the urinary metabolomic profile between IUGR and non-IUGR very preterm infants to investigate the biochemical adaptations of neonates affected by early-onset-restricted intrauterine growth.

METHODS

Neonates born <32 weeks of gestation admitted to neonatal intensive care unit (NICU) were enrolled in this prospective matched case-control study. IUGR was diagnosed by an obstetric ultra-sonographer and all relevant clinical data during NICU stay were captured. For each subject, a urine sample was collected within 48 h of life and underwent untargeted metabolomic analysis using mass spectrometry ultra-performance liquid chromatography. Data were analyzed using multivariate and univariate statistical analyses.

RESULTS

Among 83 enrolled infants, 15 IUGR neonates were matched with 19 non-IUGR controls. Untargeted metabolomic revealed evident clustering of IUGR neonates versus controls showing derangements of pathways related to tryptophan and histidine metabolism and aminoacyl-tRNA and steroid hormones biosynthesis.

CONCLUSIONS

Neonates with IUGR showed a distinctive urinary metabolic profile at birth. Although results are preliminary, metabolomics is proving to be a promising tool to explore biochemical pathways involved in this disease.

IMPACT

Very preterm infants with intrauterine growth restriction (IUGR) have a distinctive urinary metabolic profile at birth. Metabolism of glucocorticoids, sexual hormones biosynthesis, tryptophan-kynurenine, and methionine-cysteine pathways seem to operate differently in this sub-group of neonates. This is the first metabolomic study investigating adaptations exclusively in extremely and very preterm infants affected by early-onset IUGR. New knowledge on metabolic derangements in IUGR may pave the ways to further, more tailored research from a perspective of personalized medicine.

摘要

背景

宫内生长受限(IUGR)是指胎儿无法达到其遗传决定的潜能,其生化变化尚不完全清楚。本研究旨在比较 IUGR 和非 IUGR 极早产儿的尿代谢组谱,以研究受早发型受限宫内生长影响的新生儿的生化适应。

方法

本前瞻性病例对照研究纳入了胎龄<32 周、入住新生儿重症监护病房(NICU)的新生儿。IUGR 由产科超声诊断,记录 NICU 期间的所有相关临床数据。每位受试者均在生后 48 h 内采集尿液样本,采用超高效液相色谱-质谱联用进行非靶向代谢组学分析。采用多元和单变量统计分析处理数据。

结果

在 83 名入组婴儿中,15 名 IUGR 新生儿与 19 名非 IUGR 对照匹配。非靶向代谢组学显示,IUGR 新生儿与对照组存在明显聚类,表明与色氨酸和组氨酸代谢以及氨基酸酰-tRNA 和类固醇激素生物合成相关的途径发生紊乱。

结论

IUGR 新生儿在出生时表现出独特的尿代谢特征。尽管结果初步,但代谢组学已被证明是一种很有前途的探索该疾病相关生化途径的工具。

影响

宫内生长受限(IUGR)的极早产儿在出生时具有独特的尿代谢特征。糖皮质激素代谢、性激素生物合成、色氨酸-犬尿氨酸和蛋氨酸-半胱氨酸途径在这组新生儿中似乎表现不同。这是首例专门研究受早发型 IUGR 影响的极早产儿和非常早产儿代谢适应的代谢组学研究。IUGR 代谢紊乱的新知识可能为从个体化医学的角度进一步开展更具针对性的研究铺平道路。

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Gestational age-dependent development of the neonatal metabolome.新生儿代谢组学的胎龄依赖性发育。
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