Abstract
BackgroundNon-invasive prenatal testing (NIPT) has been widely used to detect common fetal chromosome aneuploidies, such as trisomy 13, 18, and 21 (T13, T18, and T21), and has expanded to sex chromosome aneuploidies (SCAs) during recent years, but few studies have reported NIPT detection of rare fetal chromosome aneuploidies (RCAs). In this study, we evaluated the clinical practical performance of NIPT to analyze all 24 chromosome aneuploidies among 57,204 pregnancies in the Suzhou area of China.MethodsThis was a retrospective analysis of prospectively collected NIPT data from two next-generation sequencing (NGS) platforms (Illumina and Proton) obtained from The Affiliated Suzhou Hospital of Nanjing Medical University. NIPT results were validated by karyotyping or clinical follow-up.ResultsNIPT using the Illumina platform identified 586 positive cases; fetal karyotyping and follow-up results validated 178 T21 cases, 49 T18 cases, 4 T13 cases, and 52 SCAs. On the Proton platform, 270 cases were positive during NIPT. Follow-up confirmed 85 T21 cases, 17 T18 cases, 4 T13 cases, 28 SCAs, and 1 fetal chromosome 22 aneuploidy case as true positives. There were 5 false-negative results, including 4 T21 and 1 T18 cases. The NGS platforms showed similar sensitivities and positive predictive values (PPVs) in detecting T21, T18, T13 and SCAs (p > 0.01). However, the Proton platform showed better specificity in detecting 45, X and the Illumina platform had better specificity in detecting T13 (p < 0.01). The major factor contributing to NIPT false-positives on the Illumina platform was false SCAs cases (65.11%). Maternal chromosome aneuploidies, maternal cancers, and confined placental mosaicism caused discordant results between fetal karyotyping and NIPT.ConclusionNIPT with NGS showed good performance for detecting T13, T18, and T21. The Proton platform had better performance for detecting SCAs, but the NIPT accuracy rate for detecting RCAs was insufficient.
Highlights
Since Lo et al first discovered cell-free fetal DNA in the plasma of pregnant women in 1997 [1], next-generation sequencing (NGS)-based non-invasive prenatal testing (NIPT) for screening of fetal chromosome aneuploidies became reality [2]
For the 138 NIPTpositive cases that were not confirmed by fetal karyotyping, 114 cases refused confirmatory diagnosis, 23 cases ended with pregnancy loss, and 1 case was loss to follow-up
Among the 114 cases who decline invasive diagnostic testing, 68 cases had normal live births, three cases ended with pregnancy loss, 1 case had Trisomy 21 (T21), 1 had an sex chromosome aneuploidies (SCAs), and 41 cases were loss to follow-up (Fig. 1)
Summary
Since Lo et al first discovered cell-free fetal DNA in the plasma of pregnant women in 1997 [1], next-generation sequencing (NGS)-based non-invasive prenatal testing (NIPT) for screening of fetal chromosome aneuploidies became reality [2]. NIPT has been widely used for detecting fetal chromosome trisomy 13, 18 and (T13, T18, and T21) and sex chromosome aneuploidies (SCAs) with high sensitivity and specificity [3,4,5]. Rare fetal chromosome aneuploidies (RCAs) involve all fetal autosomal chromosomal abnormalities other than SCAs, T13, T18, and T21. Several recent reports revealed that RCAs had great impact on prenatal diagnosis [7]. Non-invasive prenatal testing (NIPT) has been widely used to detect common fetal chromosome aneuploidies, such as trisomy 13, 18, and 21 (T13, T18, and T21), and has expanded to sex chromosome aneuploidies (SCAs) during recent years, but few studies have reported NIPT detection of rare fetal chromosome aneuploidies (RCAs). We evaluated the clinical practical performance of NIPT to analyze all 24 chromosome aneuploidies among 57,204 pregnancies in the Suzhou area of China
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