Pinto Joana, Almeida Lara Monteiro, Martins Ana Sofia, Duarte Daniela, Domingues Maria Rosário Marques, Barros António Sousa, Galhano Eulália, Pita Cristina, Almeida Maria do Céu, Carreira Isabel Marques, Gil Ana Maria
CICECO-Aveiro Institute of Materials, Department of Chemistry, University of Aveiro, Aveiro, Portugal.
Química Orgânica, Produtos Naturais e Agroalimentares Research Unit, Department of Chemistry, University of Aveiro, Aveiro, Portugal.
Am J Obstet Gynecol. 2015 Dec;213(6):841.e1-841.e15. doi: 10.1016/j.ajog.2015.07.032. Epub 2015 Jul 26.
This study aimed at determining the relationship between fetal chromosomal disorders (CDs), including trisomy 21 (T21), and on first- and second-trimester maternal blood plasma, to identify the time-course metabolic adaptations to the conditions and the possible new plasma biomarkers. Furthermore, a definition of a joint circulatory (plasma) and excretory (urine) metabolic description of second-trimester CDs was sought.
Plasma was obtained for 119 pregnant women: 74 controls and 45 CD cases, including 22 T21 cases. Plasma and lipid extracts (for T21 only) were analyzed by nuclear magnetic resonance spectroscopy, and data were handled by variable selection and multivariate analysis. Correlation analysis was used on a concatenated plasma/urine matrix descriptive of second-trimester CD, based on previously obtained urine data.
CD cases were accompanied by enhanced lipid β-oxidation (increased ketone bodies) and underutilization of glucose, pyruvate, and citrate. Lower circulating high-density lipoprotein levels were noted, along with changes in the proline and methanol in the first trimester, and also the urea, creatinine, acetate, and low-density lipoprotein plus very low-density lipoprotein in the second trimester and the different urea and creatinine levels, suggesting fetal renal dysfunction. In terms of plasma composition, T21 cases were indistinguishable from other CDs in the first trimester, whereas in the second trimester, increased methanol and albumin may be T21 specific. Furthermore, first-trimester lipid extracts of T21 showed decreased levels of 18:2 fatty acids, whereas in the second trimester, lower levels of 20:4 and 22:6 fatty acids were noted, possibly indicative of inflammation mechanisms. In both trimesters, high classification rates for CDs (88-89%) and T21 (85-92%) generally relied on variable selection of nuclear magnetic resonance data. Plasma/urine correlations confirmed most metabolic deviations and unveiled possible new ones regarding low-density lipoprotein plus very low-density lipoprotein, sugar, and gut-microflora metabolisms.
This work partially confirmed previously reported data on first-trimester T21 and provided additional information on time-course metabolic changes accompanying CD and T21, in particular regarding plasma lipid composition. These results demonstrate the potential of plasma metabolomics in monitoring and characterizing CD cases; however, validation in larger cohorts is desirable.
本研究旨在确定包括21三体（T21）在内的胎儿染色体疾病（CDs）与孕早期和孕中期孕妇血浆之间的关系，以识别对这些情况的时间进程代谢适应以及可能的新血浆生物标志物。此外，还寻求对孕中期CDs的联合循环（血浆）和排泄（尿液）代谢描述进行定义。
获取了119名孕妇的血浆：74名对照者和45名CD病例，包括22名T21病例。通过核磁共振波谱分析血浆和脂质提取物（仅针对T21），并通过变量选择和多变量分析处理数据。基于先前获得的尿液数据，对描述孕中期CD的血浆/尿液联合矩阵进行相关分析。
CD病例伴有脂质β-氧化增强（酮体增加）以及葡萄糖、丙酮酸和柠檬酸利用不足。观察到循环高密度脂蛋白水平降低，以及孕早期脯氨酸和甲醇的变化，还有孕中期尿素、肌酐、乙酸盐以及低密度脂蛋白加极低密度脂蛋白的变化，以及不同的尿素和肌酐水平，提示胎儿肾功能障碍。在血浆成分方面，T21病例在孕早期与其他CDs无法区分，而在孕中期，甲醇和白蛋白增加可能是T21特有的。此外，T21的孕早期脂质提取物显示18:2脂肪酸水平降低，而在孕中期，20:4和22:6脂肪酸水平降低，可能表明存在炎症机制。在两个孕期，CDs（88 - 89%）和T21（85 - 92%）的高分类率通常依赖于核磁共振数据的变量选择。血浆/尿液相关性证实了大多数代谢偏差，并揭示了关于低密度脂蛋白加极低密度脂蛋白、糖和肠道微生物群代谢的可能新偏差。
本研究部分证实了先前关于孕早期T21的报道数据，并提供了伴随CD和T21的时间进程代谢变化的额外信息，特别是关于血浆脂质组成。这些结果证明了血浆代谢组学在监测和表征CD病例方面的潜力；然而，需要在更大的队列中进行验证。
