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单绒毛膜双胎妊娠中的选择性胎儿生长受限:内皮损伤标志物与代谢组学特征

Selective intrauterine growth restriction in monochorionic twin pregnancies: markers of endothelial damage and metabolomic profile.

作者信息

Cosmi Erich, Visentin Silvia, Favretto Donata, Tucci Marianna, Ragazzi Eugenio, Viel Guido, Ferrara Santo Davide

机构信息

Department of Woman and Child Health, University of Padova, Padova, Italy.

出版信息

Twin Res Hum Genet. 2013 Aug;16(4):816-26. doi: 10.1017/thg.2013.33. Epub 2013 May 23.

DOI:10.1017/thg.2013.33
PMID:23701694
Abstract

The aim of this study was to assess the aorta-intima thickness (aIT) and serum metabolomic profile in selective intrauterine growth-restricted (sIUGR) monochorionic diamniotic (MCDA) twin fetuses presenting Doppler velocimetry alterations. Fetal abdominal aIT was measured by ultrasound at 32 weeks of gestation, enrolling 24 MCDA twin fetuses (8 sIUGR and 16 controls). sIUGR twin fetuses were classified into two groups: Group 1 consisted of sIUGR with abnormal umbilical artery (UA) Doppler waveforms and Group 2 included sIUGR with normal UA Doppler. Group 3 were control fetuses appropriate for gestational age (AGA). Fetal blood samples were obtained from the umbilical vein immediately after fetal extraction. A non-targeted metabolomic profiling investigated fetal metabolism alterations by using liquid chromatography-high-resolution mass spectrometry (LC-HRMS). Median fetal aIT was significantly larger in Group 1 (median value = 0.9 mm; range = 0.8-1.0 mm; p < .002) and Group 2 (median value = 0.8 mm; range = 0.7-0.8 mm; p < .002) than in AGA Group 3 (median value = 0.5 mm; range = 0.4-0.6 mm; p < .002). Metabolomic analyses, performed on four sIUGR cases (Group 1) compared with four AGA co-twins, showed an upregulation of phenylalanine, sphingosine, glycerophosphocholine, and choline, and a downregulation of valine, tryptophan, isoleucine, and proline sIUGR Group 1 compared with AGA. Although for metabolomics data only a statistical tendency (and not a statistical significance) was reached due to the small sample size, we believe that our results represent a valid starting point for further in-depth metabolomic and proteomic investigations of sIUGR in MCDA fetuses.

摘要

本研究的目的是评估出现多普勒测速改变的选择性宫内生长受限(sIUGR)单绒毛膜双羊膜囊(MCDA)双胎胎儿的主动脉内膜厚度(aIT)和血清代谢组学特征。在妊娠32周时通过超声测量胎儿腹部aIT,纳入24例MCDA双胎胎儿(8例sIUGR和16例对照)。sIUGR双胎胎儿分为两组:第1组为脐动脉(UA)多普勒波形异常的sIUGR,第2组包括UA多普勒正常的sIUGR。第3组为适于胎龄(AGA)的对照胎儿。胎儿娩出后立即从脐静脉采集胎儿血样。采用液相色谱-高分辨率质谱(LC-HRMS)进行非靶向代谢组学分析,以研究胎儿代谢改变。第1组(中位数 = 0.9 mm;范围 = 0.8 - 1.0 mm;p < 0.002)和第2组(中位数 = 0.8 mm;范围 = 0.7 - 0.8 mm;p < 0.002)的胎儿aIT中位数显著大于AGA第3组(中位数 = 0.5 mm;范围 = 0.4 - 0.6 mm;p < 0.002)。对4例sIUGR病例(第1组)与4例AGA双胎进行代谢组学分析,结果显示,与AGA相比,sIUGR第1组中苯丙氨酸、鞘氨醇、甘油磷酸胆碱和胆碱上调,缬氨酸、色氨酸、异亮氨酸和脯氨酸下调。尽管由于样本量小,代谢组学数据仅达到统计学趋势(而非统计学显著性),但我们认为我们的结果是对MCDA胎儿sIUGR进行进一步深入代谢组学和蛋白质组学研究的有效起点。

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