Porreco Richard P, Garite Thomas J, Maurel Kimberly, Marusiak Barbara, Ehrich Mathias, van den Boom Dirk, Deciu Cosmin, Bombard Allan
Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Presbyterian/St Luke's Medical Center, Obstetrix Medical Group of Colorado, Denver, CO.
University of California, Irvine, Orange, CA, and Pediatrix/Obstetrix Medical Group, Inc, Sunrise, FL/Perigen Inc, Princeton, NJ.
Am J Obstet Gynecol. 2014 Oct;211(4):365.e1-12. doi: 10.1016/j.ajog.2014.03.042. Epub 2014 Mar 19.
The objective of this study was to validate the clinical performance of massively parallel genomic sequencing of cell-free deoxyribonucleic acid contained in specimens from pregnant women at high risk for fetal aneuploidy to test fetuses for trisomies 21, 18, and 13; fetal sex; and the common sex chromosome aneuploidies (45, X; 47, XXX; 47, XXY; 47, XYY).
This was a prospective multicenter observational study of pregnant women at high risk for fetal aneuploidy who had made the decision to pursue invasive testing for prenatal diagnosis. Massively parallel single-read multiplexed sequencing of cell-free deoxyribonucleic acid was performed in maternal blood for aneuploidy detection. Data analysis was completed using sequence reads unique to the chromosomes of interest.
A total of 3430 patients were analyzed for demographic characteristics and medical history. There were 137 fetuses with trisomy 21, 39 with trisomy 18, and 16 with trisomy 13 for a prevalence rate of the common autosomal trisomies of 5.8%. There were no false-negative results for trisomy 21, 3 for trisomy 18, and 2 for trisomy 13; all 3 false-positive results were for trisomy 21. The positive predictive values for trisomies 18 and 13 were 100% and 97.9% for trisomy 21. A total of 8.6% of the pregnancies were 21 weeks or beyond; there were no aneuploid fetuses in this group. All 15 of the common sex chromosome aneuploidies in this population were identified, although there were 11 false-positive results for 45,X. Taken together, the positive predictive value for the sex chromosome aneuploidies was 48.4% and the negative predictive value was 100%.
Our prospective study demonstrates that noninvasive prenatal analysis of cell-free deoxyribonucleic acid from maternal plasma is an accurate advanced screening test with extremely high sensitivity and specificity for trisomy 21 (>99%) but with less sensitivity for trisomies 18 and 13. Despite high sensitivity, there was modest positive predictive value for the small number of common sex chromosome aneuploidies because of their very low prevalence rate.
本研究的目的是验证对胎儿非整倍体高风险孕妇样本中游离脱氧核糖核酸进行大规模平行基因组测序的临床性能，以检测胎儿是否患有21、18和13三体综合征；胎儿性别；以及常见的性染色体非整倍体（45,X；47,XXX；47,XXY；47,XYY）。
这是一项对胎儿非整倍体高风险孕妇的前瞻性多中心观察性研究，这些孕妇已决定进行侵入性检测以进行产前诊断。对孕妇血液中的游离脱氧核糖核酸进行大规模平行单读多重测序以检测非整倍体。使用感兴趣染色体特有的序列读数完成数据分析。
共分析了3430例患者的人口统计学特征和病史。有137例胎儿患有21三体综合征，39例患有18三体综合征，16例患有13三体综合征，常见常染色体三体综合征的患病率为5.8%。21三体综合征无假阴性结果，18三体综合征有3例假阴性结果，13三体综合征有2例假阴性结果；所有3例假阳性结果均为21三体综合征。18三体综合征和13三体综合征的阳性预测值为100%，21三体综合征的阳性预测值为97.9%。共有8.6%的妊娠孕周达到或超过21周；该组中无非整倍体胎儿。该人群中所有15例常见性染色体非整倍体均被识别，尽管45,X有11例假阳性结果。总体而言，性染色体非整倍体的阳性预测值为48.4%，阴性预测值为100%。
我们的前瞻性研究表明，对孕妇血浆中游离脱氧核糖核酸进行无创产前分析是一种准确的高级筛查试验，对21三体综合征具有极高的敏感性和特异性（>99%），但对18三体综合征和13三体综合征的敏感性较低。尽管敏感性高，但由于常见性染色体非整倍体的患病率极低，其阳性预测值适中。
