Integration of noninvasive DNA testing for aneuploidy into prenatal care: what has happened since the rubber met the road?
Integration of noninvasive DNA testing for aneuploidy into prenatal care: what has happened since the rubber met the road?
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DOI：
10.1373/clinchem.2013.202663
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发表时间：
2014-01
影响因子：
9.3
通讯作者：
Wilkins-Haug L
中科院分区：
文献类型：
--
作者：
Bianchi DW;Wilkins-Haug L
在过去的两年中，无创产前检测（NIPT），使用大规模平行测序来对齐和计数孕妇血浆中漂浮的DNA片段，已被整合到产前护理中。专业协会目前建议为胎儿非整倍体高风险的孕妇提供NIPT作为高级筛查，为那些风险最高的孕妇保留侵入性诊断程序。本文就常染色体和性染色体非整倍体检测的研究进展作一综述。CLIA认证的美国病理学院认可实验室的临床性能似乎与之前的临床验证研究相当，具有高灵敏度和特异性以及非常高的阴性预测值。对临床护理的主要影响是减少了侵入性手术。测试准确度受胎儿分数的影响，胎儿DNA在循环无细胞DNA总量中的百分比。胎儿分数又受到母体体重指数、胎龄、非整倍体类型、单胎与多胎以及嵌合体的影响。三项比较NIPT与血清或常染色体非整倍体联合筛查的研究均显示，即使在所有风险人群中，NIPT的假阳性率也显著较低（约0.1%）。大量的不一致阳性病例有潜在的生物学原因，包括局限性胎盘嵌合体、母体嵌合体、双胎死亡或母体恶性肿瘤。NIPT作为一种全染色体非整倍体的高级筛查方法表现良好。经济上的考虑可能决定它的使用是否可以扩大到所有的风险人群，以及它是否可以常规应用于亚染色体异常的检测。
Over the past 2 years, noninvasive prenatal testing (NIPT), which uses massively parallel sequencing to align and count DNA fragments floating in the plasma of pregnant women, has become integrated into prenatal care. Professional societies currently recommend offering NIPT as an advanced screen to pregnant women at high risk for fetal aneuploidy, reserving invasive diagnostic procedures for those at the very highest risk. In this review, we summarize the available information on autosomal and sex chromosome aneuploidy detection. Clinical performance in CLIA-certified, College of American Pathology–accredited laboratories appears to be equivalent to prior clinical validation studies, with high sensitivities and specificities and very high negative predictive values. The main impact on clinical care has been a reduction in invasive procedures. Test accuracy is affected by the fetal fraction, the percentage of fetal DNA in the total amount of circulating cell-free DNA. Fetal fraction is in turn affected by maternal body mass index, gestational age, type of aneuploidy, singleton vs multiples, and mosaicism. Three studies comparing NIPT to serum or combined screening for autosomal aneuploidy all show that NIPT has significantly lower false-positive rates (approximately 0.1%), even in all-risk populations. A significant number of the discordant positive cases have underlying biological reasons, including confined placental mosaicism, maternal mosaicism, cotwin demise, or maternal malignancy. NIPT performs well as an advanced screen for whole chromosome aneuploidy. Economic considerations will likely dictate whether its use can be expanded to all risk populations and whether it can be applied routinely for the detection of subchromosome abnormalities.