母血浆非性别依赖胎儿游离DNA对早期预测子痫前期价值的研究

子痫前期是最严重的妊娠并发症之一，是导致孕产妇和围产儿死亡的最主要原因之一。对子痫前期早期预测并早期干预可减少或避免不良母婴结局。目前子痫前期的预测方法多种，但检测的特异性及灵敏度均不是很高。研究发现，子痫前期孕妇血浆胎儿游离DNA(cffDNA)在早孕期含量增加及产后清除率降低，提示母血中cffDNA浓度可用来预测子痫前期的发生及预后。本研究连续采集40例正常孕妇和20例子痫前期患者不同孕周外周血，通过第二代测序平台建立正常妊娠和子痫前期孕妇外周血cffDNA含量动态变化曲线。通过生物信息学分析，寻找cffDNA在子痫前期患者外周血浆浓度上升过程中在人类全基因组的分布规律，寻找潜在的cffDNA富集区域，探索可能与子痫前期发病相关的基因特异性。通过对比子痫前期患者产后血浆中留存cffDNA的基因位置，研究cffDNA清除速率降低的可能分子通路机制，评价cffDNA对子痫前期预测价值。

Preeclampsia is one of the major causes of maternal and perinatal morbidity and mortality. Effective screening for early detection of pregnancies that are destined to experience preeclampsia is important to estimate their proximity to onset of the clinical disease, and would permit medical care providers to plan a more detailed course of action. Currently, a wide variety of markers have been proposed to predict preeclampsia, however, most of them do not have highly enough sensitivity and specificity. Several studies show that the quantitative changes of cell-free fetal DNA (cffDNA) in maternal plasma, such as elevated levels of cffDNA during first trimester of pregnancies and slow clearance of cffDNA after deliveries, can be used as an effective indicator for impending preeclampsia. We propose to continuously measure the concentrations of cffDNA from 40 normal pregnancies and 20 cases with preeclampsia using the next-generation sequencing (NGS) platform. From NGS data, we could accurately demonstrate the changing patterns of cffDNA concentration levels in different gestational age from the plasma of normal pregnancies and preeclampsia patients. Also, we hope to examine the cffDNA genomic coverage and gene content differences between the case and control samples using the NGS data, which may lead to the further understanding of the cffDNA metabolism and the possible function impact of cffDNA and preeclampsia in the molecular level.