Section for Clinical Mass Spectrometry, Department of Congenital Disorders, Danish Center for Neonatal Screening, Statens Serum Institut, Copenhagen, Denmark.
iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Copenhagen, Denmark.
Pediatr Res. 2021 May;89(6):1396-1404. doi: 10.1038/s41390-020-01149-z. Epub 2020 Sep 17.
Prematurity is a severe pathophysiological condition, however, little is known about the gestational age-dependent development of the neonatal metabolome.
Using an untargeted liquid chromatography-tandem mass spectrometry metabolomics protocol, we measured over 9000 metabolites in 298 neonatal residual heel prick dried blood spots retrieved from the Danish Neonatal Screening Biobank. By combining multiple state-of-the-art metabolome mining tools, we retrieved chemical structural information at a broad level for over 5000 (60%) metabolites and assessed their relation to gestational age.
A total of 1459 (~16%) metabolites were significantly correlated with gestational age (false discovery rate-adjusted P < 0.05), whereas 83 metabolites explained on average 48% of the variance in gestational age. Using a custom algorithm based on hypergeometric testing, we identified compound classes (617 metabolites) overrepresented with metabolites correlating with gestational age (P < 0.05). Metabolites significantly related to gestational age included bile acids, carnitines, polyamines, amino acid-derived compounds, nucleotides, phosphatidylcholines and dipeptides, as well as treatment-related metabolites, such as antibiotics and caffeine.
Our findings elucidate the gestational age-dependent development of the neonatal blood metabolome and suggest that the application of metabolomics tools has great potential to reveal novel biochemical underpinnings of disease and improve our understanding of complex pathophysiological mechanisms underlying prematurity-associated disorders.
A large variation in the neonatal dried blood spot metabolome from residual heel pricks stored at the Danish Neonatal Screening Biobank can be explained by gestational age. While previous studies have assessed the relation of selected metabolic markers to gestational age, this study assesses metabolome-wide changes related to prematurity. Using a combination of recently developed metabolome mining tools, we assess the relation of over 9000 metabolic features to gestational age. The ability to assess metabolome-wide changes related to prematurity in neonates could pave the way to finding novel biochemical underpinnings of health complications related to preterm birth.
早产是一种严重的病理生理状况，但人们对新生儿代谢组随胎龄的变化知之甚少。
我们使用非靶向液相色谱-串联质谱代谢组学方法，测量了来自丹麦新生儿筛查生物库的 298 个新生儿足跟残留血斑中超过 9000 种代谢物。通过结合多种最先进的代谢组学挖掘工具，我们广泛地检索了 5000 多种（60%）代谢物的化学结构信息，并评估了它们与胎龄的关系。
共有 1459 种（约 16%）代谢物与胎龄显著相关（经错误发现率校正的 P < 0.05），而 83 种代谢物平均解释了胎龄 48%的变异性。使用基于超几何检验的定制算法，我们确定了与胎龄相关的代谢物中过度表达的化合物类别（617 种代谢物）（P < 0.05）。与胎龄显著相关的代谢物包括胆汁酸、肉碱、多胺、氨基酸衍生化合物、核苷酸、磷脂酰胆碱和二肽，以及治疗相关的代谢物，如抗生素和咖啡因。
我们的研究结果阐明了新生儿血代谢组随胎龄的变化，并表明代谢组学工具的应用具有揭示疾病新的生化基础的巨大潜力，并有助于我们理解与早产相关疾病的复杂病理生理机制。
从丹麦新生儿筛查生物库中存储的足跟残留血斑中可以解释新生儿干血斑代谢组的巨大差异与胎龄有关。虽然之前的研究已经评估了选定代谢标志物与胎龄的关系，但本研究评估了与早产相关的代谢组变化。我们使用最近开发的代谢组学挖掘工具组合，评估了超过 9000 种代谢物与胎龄的关系。评估与早产相关的代谢组变化的能力可能为寻找与早产相关的健康并发症的新的生化基础铺平道路。
