Analysis of cell-free DNA in a consecutive series of 13,607 routine cases for the detection of fetal chromosomal aneuplo
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MATERNAL-FETAL MEDICINE
Analysis of cell‑free DNA in a consecutive series of 13,607 routine cases for the detection of fetal chromosomal aneuploidies in a single center in Germany Heike Borth1 · Anna Teubert2 · Ralf Glaubitz2 · Sarah Knippenberg2 · Nargül Kutur1 · Thomas Winkler1 · Bernd Eiben1 Received: 22 April 2020 / Accepted: 20 October 2020 © The Author(s) 2020
Abstract Purpose Noninvasive prenatal testing (NIPT) is a highly sensitive and specific method for detection of fetal chromosomal aneuploidies from maternal plasma. The objective of this study was to determine the performance of a new paired-end sequencing-based NIPT assay in 13,607 pregnancies from a single center in Germany. Methods Samples from 13,607 pregnant women who previously underwent NIPT were analyzed using VeriSeq NIPT Solution v2 assay for presence of common fetal trisomies and monosomy X. Follow-up to determine clinical truth was carried out. Results Of the 13,607 cases, 13,509 received a NIPT call resulting in a low study failure rate of 0.72%. There were 188 (1.4%) high-risk calls: 117 trisomy 21, 34 trisomy 18, 23 trisomy 13, one trisomy 21 + 13, and 13 monosomy X. High sensitivities and specificities of ≥ 98.89% were reported for all four aneuploidy conditions. Of the high-risk cases, clinical follow-up data were available for 77.1% (145/188). Clinical follow-up of high-risk calls revealed an overall positive predictive value of 84.8% (potential range 65.4–88.3%). NIPT results were provided for samples across a range of fetal fractions, down to 2% fetal fraction. Conclusion The VeriSeq NIPT Solution v2 assay detected fetal chromosomal aneuploidies across a range of fetal fractions with high sensitivities and specificities observed based on known clinical outcomes, a high overall PPV, and a low failure rate. Keywords Noninvasive prenatal testing · Fetal chromosomal aneuploidies · Fetal fraction · Positive predictive value · VeriSeq NIPT Solution
Introduction The discovery of fetal cell-free DNA (cfDNA) in maternal circulation in 1997 [1] facilitated the development and commercial availability of noninvasive prenatal testing (NIPT) assays to screen for the presence of fetal chromosomal anomalies. These NIPT assays have been shown to have superior performance over traditional serum Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00404-020-05856-0) contains supplementary material, which is available to authorized users. * Bernd Eiben [email protected] 1
Amedes Institut für Labormedizin und Klinische Genetik Rhein/Ruhr, Willy Brandt Platz 4, 45127 Essen, Germany
Amedes Genetics, Georgstr. 50, 30159 Hannover, Germany
2
screening methods [2]; a recent meta-analysis found that NIPT could detect at least 98% of common fetal trisomies in singleton pregnancies with a combined false-positive rate of 0.13% [3]. The use of NIPT in the general pregnancy population has been endorsed by a number of professional societies, including the German Society of Human Genetics [4–7], and recom
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