Noninvasive prenatal testing for chromosome aneuploidies and subchromosomal microdeletions/microduplications in a cohort of 8141 single pregnancies

Abstract

BackgroundNoninvasive prenatal testing (NIPT) for fetal aneuploidies by scanning cell-free fetal DNA in maternal plasma is rapidly becoming a first-tier aneuploidy screening test in clinical practices. With the development of whole-genome sequencing technology, small subchromosomal deletions and duplications that could not be detected by conventional karyotyping are now able to be detected with NIPT technology.MethodsIn the present study, we examined 8141 single pregnancies with NIPT to calculate the positive predictive values of each of the chromosome aneuploidies and the subchromosomal microdeletions and microduplications.ResultsWe confirmed that the positive predictive values (PPV) for trisomy 13, trisomy 18, trisomy 21, and sex chromosome aneuploidy were 14.28%, 60%, 80%, and 45.83%, respectively. At the same time, we also found 51 (0.63%) positive cases for chromosomal microdeletions or microduplications but only 13 (36.11%) true-positive cases. These results indicate that NIPT for trisomy 21 detection had the highest accuracy, while accuracy was low for chromosomal microdeletion and microduplications.ConclusionsTherefore, it is very important to improve the specificity, accuracy, and sensitivity of NIPT technology for the detection of subchromosomal microdeletions and microduplications.

Clinical Experience with Fetal Sex Chromosome Aneuploidy Identified by Non-Invasive Prenatal Testing in 45773 Cases

“…Therefore, genetic counseling combined with serum biochemical screening and ultrasound detection of abnormalities, should be fully carried out for advanced-age pregnant women. The incidences of 45,X and 47,XYY were signi cantly correlated with maternal age, whereas those of 47,XXX and 47,XXY did not show signi cant correlations [5,35] . Although there was no statistical signi cance between the incidence of 47,XYY and the maternal age, but it observed that the incidence of 47,XYY decreased with maternal age in the advanced aged group.…”

“…Our study showed that NIPT performed better in predicting sex chromosome trisomies than monosomy X. This is potentially because the low guanosine-cytosine content of the X chromosome leads to highly variable ampli cation of the X chromosome, as well as the occurrence of age-related X chromosome loss in normal female white blood cells [5] . The PPV of SCA is lower than other common chromosome aneuploidy.…”

“…The PPV of SCA is lower than other common chromosome aneuploidy. The reason is that sex chromosome abnormalities are less prevalent [5] . With regard to the discordance between NIPT and invasive prenatal testing, the explanations are as follows.…”

“…Extensive studies have demonstrated the high sensitivity and speci city of NIPT in screening T21, T18 and T13, with sensitivities of 95.9%, 86.5%, and 77.5% and speci cities of 99.9%, 99.8%, and 99.9%, respectively [4] . Research has suggested that the PPV of T21, T18, and T13 were 65-94%, 47-85%, and 12-62%, respectively [5] .…”

“…With the implementation of the second-child policy in China in 2014, the rate of pregnancy in women aged ≥ 35 years has gradually increased [5] . At present, it is generally believed that advanced maternal age is an important risk factor in chromosomal abnormalities [16] .…”