Noninvasive Prenatal Testing for Fetal XXY Aneuploidies Among Pregnancies in Beijing of China

Abstract

Abstract Objective: To evaluate the screening performance of noninvasive prenatal testing (NIPT) based on high-throughput massively parallel sequencing technology for the fetal XXY aneuploidies among pregnancies in Beijing of China. Methods: The study enrolled 26 913 consecutive pregnancies, 20–50 years old, who attended the Peking Union Medical College Hospital, Beijing, China, for prenatal screening from January 1, 2016 to December 31, 2019. Cell-free DNA was extracted from maternal peripheral blood to have a high-throughput massively parallel sequencing procedure. Cases with high-risk of fetal XXY were suggested to take invasive prenatal diagnosis (IPD) for confirmation. Maternal DNA sequencing was performed, if necessary, to find other potential factors that may lead to high-risk results of XXY by NIPT. Results: Among a cohort of 26 913 pregnant women, 34 were high-risk for fetal XXY, among which 30 accepted IPD while 4 declined. In those who accepted IPD, 19 cases were confirmed fetal XXY by chromosome karyotyping analysis while 11 were verified as false positive. Among the 19 confirmed fetal XXY cases, 14 elected pregnancy termination. For all the 34 high-risk cases, two were verified maternal sex chromosome aneuploidy. The calculated detection rate, positive predictive value, and false-positive rate of NIPT for fetal XXY in this cohort was 100.00% (19/19), 63.33% (19/30), and 0.04% (11/26 890), respectively. And the percentage of pregnancy termination was 73.68% (14/19). Conclusion: NIPT could be used as a potential method for fetal XXY screening, although the accuracy needs to be improved. As NIPT is not diagnostic, IPD is strongly recommended for those with high-risk results. For cases with discordance between NIPT and fetal karyotyping, maternal DNA sequencing would help to identify the cause of false-positive/false-negative results.