孕染色体非整倍体孕妇分娩后血浆胎儿游离DNA清除规律的研究

Clearance of free fetal DNA after delivery of fetuses carrying chromosomal aneuploidies

目的探讨孕染色体非整倍体孕妇分娩后血浆胎儿游离DNA的清除规律。方法募集10例孕18～25周的单胎妊娠孕妇，羊水培养确定胎儿核型为21三体8例和18三体2例，在终止妊娠前、终止妊娠胎儿分娩后15min、30min、60min、120min、3h、6h、9h、12h、24h、48h、72h分别抽取外周血5mL分离血浆，对胎儿游离DNA进行高通量测序。结果孕妇血浆中21一三体或18-三体胎儿游离DNA于分娩后快速被清除，产后O～2h的平均半衰期约为1．24h，产后6～72h为缓慢清除期，平均半衰期约为11．70h，72h后检测不到胎儿游离DNA。结论孕染色体非整倍体孕妇分娩后胎儿游离DNA量下降迅速，于72h内消失，该结果为无创DNA检测染色体非整倍体技术的临床应用和产前临床咨询提供了理论依据。

Objective To explore the rules for free fetal DNA clearance after delivery of fetuses carrying chromosomal aneuploidies. Methods For 10 women carrying 18-to-25-gestation-week singletons confirmed to have chromosomal abnormalities by amniotic karyotyping, 5 mL of peripheral venous blood was drawn respectively before and 15 minutes, 30 minutes, 60 minutes, 120 minutes, 3 hours, 6 hours, 9 hours, 12 hours, 24 hours, 48 hours and 72 hours after their elective termination of pregnancies. Free fetal DNA was isolated from the plasma and subjected to high throughput sequencing. Results Statistical analysis of the sequence information showed that the free DNA of fetuses with trisomy 21 or 18 was rapidly cleared after delivery. The average halfqife was approximately 1. 24 hours within the first 2 hours after delivery. It was then slowly cleared between 6 and 72 hours, with an average half-life of 11.70 hours. No fetal DNA was detectable 72 hours after delivery. Conclusion Free fetal DNA rapidly decreases after delivery and will completely disappear by 72 hours. Above results may provide a basis for clinical application of the non-invasive detection of chromosomal aneuploidies during prenatal diagnosis.