Abstract
PurposeNoninvasive 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.MethodsSamples 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.ResultsOf 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.ConclusionThe 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.
Highlights
The discovery of fetal cell-free DNA 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
The existing sequencing files from the original sample analysis were reanalyzed using the bioinformatic pipeline of the new NIPT assay, VeriSeq NIPT Solution v2, being implemented in the laboratory
86.6% of patients presented for testing in their first trimester; the relationship between gestational age and other patient characteristics is shown in Supplementary Fig. 1 (Online Resource 2)
Summary
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. NIPT assays screened for the presence of common fetal trisomies only, i.e., trisomy 21, trisomy 18, and trisomy 13 [10, 11] This was expanded to include optional testing for fetal sex and sex chromosome aneuploidies [12, 13], and later to include the option of screening for common microdeletions [14, 15], rare autosomal aneuploidies, and partial deletions and duplications [16,17,18]. Several studies have shown the use of this type of sequencing in the noninvasive screening of fetal chromosomal aneuploidies [26, 27], and the first paper on clinical use of paired-end sequencing was published in 2017 [28]
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