Demko Zachary, Prigmore Brittany, Benn Peter
Natera, Inc., San Carlos, CA 94070, USA.
Department of Genetics and Genome Sciences, UConn Health, Farmington, CT 06030, USA.
J Clin Med. 2022 Aug 15;11(16):4760. doi: 10.3390/jcm11164760.
Non-invasive prenatal testing (NIPT) for trisomies 21, 18, 13 and monosomy X is widely utilized with massively parallel shotgun sequencing (MPSS), digital analysis of selected regions (DANSR), and single nucleotide polymorphism (SNP) analyses being the most widely reported methods. We searched the literature to find all NIPT clinical validation and clinical experience studies between January 2011 and January 2022. Meta-analyses were performed using bivariate random-effects and univariate regression models for estimating summary performance measures across studies. Bivariate meta-regression was performed to explore the influence of testing method and study design. Subgroup and sensitivity analyses evaluated factors that may have led to heterogeneity. Based on 55 validation studies, the detection rate (DR) was significantly higher for retrospective studies, while the false positive rate (FPR) was significantly lower for prospective studies. Comparing the performance of NIPT methods for trisomies 21, 18, and 13 combined, the SNP method had a higher DR and lower FPR than other methods, significantly so for MPSS, though not for DANSR. The performance of the different methods in the 84 clinical experience studies was consistent with validation studies. Clinical positive predictive values of all NIPT methods improved over the last decade. We conclude that all NIPT methods are highly effective for fetal aneuploidy screening, with performance differences across methodologies.
用于21三体、18三体、13三体和X单体的无创产前检测（NIPT）被广泛应用，其中大规模平行鸟枪法测序（MPSS）、选定区域数字分析（DANSR）和单核苷酸多态性（SNP）分析是报道最为广泛的方法。我们检索了文献，以查找2011年1月至2022年1月期间所有NIPT临床验证和临床经验研究。使用双变量随机效应模型和单变量回归模型进行荟萃分析，以估计各项研究的汇总性能指标。进行双变量元回归以探讨检测方法和研究设计的影响。亚组分析和敏感性分析评估了可能导致异质性的因素。基于55项验证研究，回顾性研究的检测率（DR）显著更高，而前瞻性研究的假阳性率（FPR）显著更低。比较21三体、18三体和13三体联合检测的NIPT方法性能，SNP方法的DR更高，FPR更低，与MPSS相比差异显著，但与DANSR相比差异不显著。84项临床经验研究中不同方法的性能与验证研究一致。在过去十年中，所有NIPT方法的临床阳性预测值均有所提高。我们得出结论，所有NIPT方法对胎儿非整倍体筛查都非常有效，但不同方法的性能存在差异。
