Non-invasive prenatal testing to detect chromosome aneuploidies in 57,204 pregnancies

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). 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.

This 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.

NIPT 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.

NIPT 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.