Farina Antonio, Sekizawa Akihiko, Sugito Yumi, Iwasaki Mariko, Jimbo Masatoshi, Saito Hiroshi, Okai Takashi
Department of Obstetrics and Gynecology, Showa University School of Medicine, Tokyo, Japan.
Prenat Diagn. 2004 Feb;24(2):83-6. doi: 10.1002/pd.788.
Our objective was to examine whether plasma fetal DNA can be used as a screening variable in those women who developed preeclampsia but without any clinical symptom at the time of blood draw.
Fetal DNA was extracted from 1.5-mL plasma samples, and the DYS14 gene was analyzed by real-time quantitative polymerase chain reaction. Plasma collected and frozen from six women were each paired with five matched control samples of identical specimen type from gravid women carrying a presumed normal male fetus. Matched rank-sum analysis and nonparametric receiver operating characteristic (ROC) curves analysis of estimated multiples of median (MoM) were used for calculating detection rate (DR) and false-positive rate (FPR).
The mean observed rank of 5.08 in the cases was significantly higher than the expected 3.18 (p-value = 0.013). Pregnancies that will develop a preeclampsia exhibit 2.39-fold higher levels of maternal plasma cell-free fetal DNA compared to matched controls. DR was 33 and 50% at an FPR of 5 and 10% respectively.
The estimated DR allows to consider fetal DNA as a potential variable to predict preeclampsia in a low-risk population. Further studies will be addressed to calculate a parametric statistical algorithm and to estimate a proper posterior risk of the disease by means of fetal DNA alone or combined with other markers.
我们的目的是研究血浆胎儿DNA是否可作为那些发生先兆子痫但在采血时无任何临床症状的女性的筛查变量。
从1.5毫升血浆样本中提取胎儿DNA,并通过实时定量聚合酶链反应分析DYS14基因。从六名女性收集并冷冻的血浆分别与来自携带假定正常男性胎儿的妊娠女性的五个匹配的相同样本类型的对照样本配对。使用估计中位数倍数(MoM)的匹配秩和分析和非参数接收者操作特征(ROC)曲线分析来计算检测率(DR)和假阳性率(FPR)。
病例组中观察到的平均秩次5.08显著高于预期的3.18(p值=0.013)。与匹配对照组相比,将发生先兆子痫的妊娠孕妇血浆中无细胞胎儿DNA水平高2.39倍。在假阳性率为5%和10%时,检测率分别为33%和50%。
估计的检测率使得可以将胎儿DNA视为预测低风险人群先兆子痫的潜在变量。后续研究将致力于计算参数统计算法,并通过单独使用胎儿DNA或与其他标志物联合使用来估计该疾病的适当后验风险。