Prediction of pre-eclampsia by an analysis of placenta-derived cellular mRNA in the blood of pregnant women at 15-20 weeks of gestation

Prediction of pre-eclampsia by an analysis of placenta-derived cellular mRNA in the blood of pregnant women at 15-20 weeks of gestation
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DOI:
10.1111/j.1471-0528.2010.02491.x
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发表时间:
2010-04-01
影响因子:
5.8
通讯作者:
Okai, T.
Okai, T.
中科院分区:
医学1区
文献类型:
--
作者:
Sekizawa, A.;Purwosunu, Y.;Okai, T.

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目的 利用一组细胞 mRNA 标记物预测妊娠 15-20 周孕妇发生先兆子痫。设计前瞻性队列研究。地点印度尼西亚大学妇产科,印度尼西亚 Cipto Mangunkusumo 国立医院。样本取自无症状孕妇的外周血样本。方法在 660 名妇女中,62 名在妊娠后期发生先兆子痫。 (先兆子痫组)每个病例与五个对照相匹配。因此,将62名先兆子痫女性与310名对照者的母血细胞成分中的RNA表达水平进行比较。 主要结果指标比较先兆子痫组与对照组之间与血管生成和氧化应激相关基因的细胞RNA表达水平。使用受试者工作特征(ROC)曲线来分析每个可用标志物的敏感性。采用逻辑回归分析计算每位女性被分类为病例的几率。结果单变量 ROC 分析确定可溶性血管内皮生长因子受体 1 (Flt-1) 和内皮糖蛋白 (ENG) 为敏感性最高的标记物。结合Flt-1、ENG、胎盘生长因子(PlGF)和胎次获得最佳多变量模型。相对 ROC 曲线的灵敏度为 66%,特异性为 10%,曲线下面积为 0.884(P < 0.001)。 结论母体血液中的一组细胞 mRNA 标记物可以在临床发病前很久预测先兆子痫的发展。
ObjectiveA panel of cellular mRNA markers was used to predict the occurrence of pre-eclampsia in pregnant women at 15-20 weeks of gestation.DesignProspective cohort study.SettingThe Department of Obstetrics and Gynaecology, University of Indonesia, Cipto Mangunkusumo National Hospital, Indonesia.SamplePeripheral blood samples from asymptomatic pregnant women.MethodsAmong 660 women, 62 developed pre-eclampsia at later gestation (pre-eclampsia group) and each case was matched with five controls. Therefore, the RNA expression levels in the cellular component of maternal blood in 62 women with pre-eclampsia were compared with those in 310 controls.Main outcome measuresThe cellular RNA expression levels of genes related to angiogenesis and oxidative stress were compared between pre-eclampsia and control groups. A receiver operating characteristic (ROC) curve was used to analyse the sensitivity of each available marker. A logistic regression analysis was performed to calculate the odds for each woman to be classified as a case.ResultsThe univariate ROC analysis identified soluble vascular endothelial growth factor receptor-1 (Flt-1) and endoglin (ENG) as the markers with the highest sensitivity. The best multivariate model was obtained by combining Flt-1, ENG, placental growth factor (PlGF) and parity. The relative ROC curve yielded a sensitivity of 66% at a 10% 1 - specificity rate with an area under the curve of 0.884 (P < 0.001).ConclusionA panel of cellular mRNA markers in maternal blood can predict the development of pre-eclampsia long before clinical onset.