Clinical Performance of Cell-Free Fetal DNA Testing for Fetal Aneuploidies and Subchromosomal Deletions/Duplications in a Cohort of 19,531 Pregnancies

Objective:We aim to assess the clinical performance of cell-free fetal DNA(cffDNA)testing for detecting common fetal aneuploidies as well as subchromosomal deletions/duplications and explore the pregnancy decisions in screen-positive cases.Methods:A cohort of 19,531 pregnant women was offered cffDNA testing for detection of trisomies 21,18,and 13(T21,T18,and T13);sex chromosome aneuploidies(SCAs);and subchromosomal deletions/duplications.Screen-positive cases were confirmed by karyotyping and single-nucleotide polymorphism array analysis.Results:A total of 47 cases failed the test.The overall screen-positive rate of chromosomal abnormalities was 1.07%(208/19,484),including 57 cases with T21,18 cases with T18,7 cases with T13,106 cases with SCAs,and 20 cases of subchromosomal deletions/duplications.Positive predictive values were 91.30%(42/46),38.46%(5/13),33.33%(2/6),41.33%(31/75),and 27.78%(5/18),respectively.There was no significant difference in the screening of fetal chromosomal aneuploidies in the high-risk group compared with the low-risk group(P>0.05).All of the pregnant women who had confirmed fetal T21,T18,or T13 terminated their pregnancies,except for a case of T13 mosaic,whereas 45.16%(14/31)of women with fetal SCAs continued their pregnancies.Furthermore,17 pregnant women with positive screens for T21,T18,or T13 without a subsequent diagnosis chose to terminate their pregnancy,whereas 29 of 31 women with SCAs chose to continue their pregnancies.Conclusions:CffDNA testing exhibited good screening accuracy for T21,T18,and T13 and also contributed to detecting fetal SCAs and subchromosomal deletions/duplications.Pregnant women with fetal 47,XXX or 47,XYY were more willing to terminate their pregnancy than those with fetal 45,X or 47,XXY.

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

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 26913 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 26913 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%(11/26890),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.