Mother Infant Research Institute at Tufts Medical Center and Floating Hospital for Children and Departments of Pediatrics and Obstetrics and Gynecology, Tufts University School of Medicine, Boston, MA;
Clin Chem. 2014 Jan;60(1):78-87. doi: 10.1373/clinchem.2013.202663. Epub 2013 Nov 19.
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.
在过去的 2 年中，非侵入性产前检测（NIPT）已成为产前护理的一部分，它使用大规模并行测序来对齐和计数孕妇血浆中漂浮的 DNA 片段。专业协会目前建议向高风险胎儿非整倍体的孕妇提供 NIPT 作为高级筛查，将侵入性诊断程序保留给风险最高的孕妇。
在这篇综述中，我们总结了常染色体和性染色体非整倍体检测的可用信息。CLIA 认证、美国病理学会认证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程序。测试准确性受胎儿分数的影响，即胎儿 DNA 在总循环无细胞 DNA 中的百分比。胎儿分数又受母体体重指数、妊娠年龄、非整倍体类型、单胎与多胎以及嵌合体的影响。三项比较 NIPT 与血清或联合筛查常染色体非整倍体的研究均表明，NIPT 的假阳性率（约 0.1%）明显较低，即使在所有风险人群中也是如此。大量不一致的阳性病例有潜在的生物学原因，包括胎盘嵌合体、母体嵌合体、双胎死亡或母体恶性肿瘤。
NIPT 作为全染色体非整倍体的高级筛查表现良好。经济因素可能决定其是否可以扩展到所有风险人群，以及是否可以常规用于检测亚染色体异常。
