Division of Maternal Fetal Medicine, William Beaumont Health, Royal Oak, MI, USA.
Center for Data Science,DePaul University School of Computing, Chicago, IL, USA.
J Matern Fetal Neonatal Med. 2022 Dec;35(25):6380-6387. doi: 10.1080/14767058.2021.1914572. Epub 2021 May 4.
To identify maternal second and third trimester urine metabolomic biomarkers for the detection of fetal congenital heart defects (CHDs).
This was a prospective study. Metabolomic analysis of randomly collected maternal urine was performed, comparing pregnancies with isolated, non-syndromic CHDs versus unaffected controls. Mass spectrometry (liquid chromatography and direct injection and tandem mass spectrometry, LC-MS-MS) as well as nuclear magnetic resonance spectrometry, H NMR, were used to perform the analyses between 14 0/7 and 37 0/7 weeks gestation. A total of 36 CHD cases and 41 controls were compared. Predictive algorithms using urine markers alone or combined with, clinical and ultrasound (US) (four-chamber view) predictors were developed and compared.
A total of 222 metabolites were identified, of which 16 were overlapping between the two platforms. Twenty-three metabolite concentrations were found in significantly altered in CHD gestations on univariate analysis. The concentration of methionine was most significantly altered. A predictive algorithm combining metabolites (histamine, choline, glucose, formate, methionine, and carnitine) plus US four-chamber view achieved an AUC = 0.894; 95% CI, 0814-0.973 with a sensitivity of 83.8% and specificity of 87.8%. Enrichment pathway analysis identified several lipid related pathways that are dysregulated in CHD, including phospholipid biosynthesis, phosphatidylcholine biosynthesis, phosphatidylethanolamine biosynthesis, and fatty acid metabolism. This could be consistent with the increased risk of CHD in diabetic pregnancies.
We report a novel, noninvasive approach, based on the analysis of maternal urine for isolated CHD detection. Further, the dysregulation of lipid- and folate metabolism appears to support prior data on the mechanism of CHD.
鉴定母体第二和第三孕期尿液代谢组学生物标志物，以检测胎儿先天性心脏病（CHD）。
这是一项前瞻性研究。对随机采集的母体尿液进行代谢组学分析，比较孤立性、非综合征性 CHD 妊娠与无影响对照组。使用质谱（液相色谱和直接进样串联质谱，LC-MS-MS）以及核磁共振谱，H NMR，在 14 0/7 至 37 0/7 孕周之间进行分析。共比较了 36 例 CHD 病例和 41 例对照。开发并比较了仅使用尿液标志物或结合临床和超声（US）（四腔心切面）预测因子的预测算法。
共鉴定出 222 种代谢物，其中两种平台之间有 16 种重叠。在单变量分析中，23 种代谢物浓度在 CHD 妊娠中发生显著改变。蛋氨酸浓度改变最为显著。结合代谢物（组氨酸、胆碱、葡萄糖、甲酸盐、蛋氨酸和肉碱）和 US 四腔心切面的预测算法获得 AUC = 0.894；95%CI，0814-0.973，灵敏度为 83.8%，特异性为 87.8%。富集途径分析确定了几种脂质相关途径在 CHD 中失调，包括磷脂生物合成、磷脂酰胆碱生物合成、磷脂酰乙醇胺生物合成和脂肪酸代谢。这与糖尿病妊娠中 CHD 风险增加相一致。
我们报告了一种新的、非侵入性的方法，基于母体尿液分析检测孤立性 CHD。此外，脂质和叶酸代谢的失调似乎支持 CHD 发生机制的先前数据。
