Clinical experience regarding the accuracy of NIPT in the detection of sex chromosome abnormality

Zheng, Yijing; Wan, Shanning; Dang, Yinghui; Song, Tingting; Chen, Biliang; Zhang, Jianfang

doi:10.1002/jgm.3199

Cited by 25 publications

(29 citation statements)

References 19 publications

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“…Among the 72 SCA samples detected, the detection rate of SCA was 0.28% and the PPV was 41.07%, among which the number of true positive cases was 3, 6, 8 and 6 for 45,X, 47,XXY, 47,XXX and 47,XYY, respectively, and their PPVs were 12.00%, 50.00%, 72.73% and 75.00%, respectively. The detection efficacy of NIPT for SCA was not as good as its efficacy for autosomal aneuploidy, with the lowest detection efficacy for 45,X (PPV: 12.00%) and moderate detection efficacy for 47,XXY, 47,XXX, and 47,XYY (PPV: 64.52%), which is in general agreement with the literature (62.70%) [ 19 ]. The high homology of X and Y chromosomes is not conducive to detection, and many segments of Y chromosome are similar to other chromosomes, which reduces the accuracy of sequencing.…”

Section: Discussionsupporting

confidence: 88%

Clinical application of noninvasive prenatal testing in the detection of fetal chromosomal diseases

Chaohong²,

Tang³

et al. 2021

Mol Cytogenet

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Objective To assess the detection efficiency of noninvasive prenatal testing (NIPT) for fetal autosomal aneuploidy, sex chromosome aneuploidy (SCA), other chromosome aneuploidy, copy number variation (CNV), and to provide further data for clinical application of NIPT. Materials and methods 25,517 pregnant women who underwent NIPT testing in Anhui Province Maternity and Child Health Hospital from September 2019 to September 2020 were selected, and samples with high-risk test results were subjected to karyotype analysis for comparison by using amniotic fluid, with some samples subjected to further validation by chromosomal microarray analysis, and followed up for pregnancy outcome. Results A total of 25,517 pregnant women who received NIPT, 25,502 cases were tested successfully, and 294 high-risk samples (1.15%) were detected, there were 96 true positive samples, 117 false positive samples and 81 cases were refused further diagnosis. Samples with high risk of autosomal aneuploidy were detected in 71 cases (0.28%), and 51 cases were confirmed, including: trisomy 21 (T21) in 44 cases, trisomy 18 (T18) in 5 cases, and trisomy 13 (T13) in 2 cases; the positive predictive value (PPV) was 91.67%, 45.45%, and 33.33%, respectively, and the negative predictive value was 100%, the false positive rate (FPR) was 0.02%, 0.02%, and 0.02%, respectively.13 samples with high risk of mosaic trisomies 21, 18, and 13 were detected, and 1 case of T21mos was confirmed with a PPV of 8.33%. Samples with high risk of SCA were detected in 72 cases (0.28%), and the diagnosis was confirmed in 23 cases, with a PPV of 41.07% and a FPR of 0.13%. These included 3 cases of 45,X, 6 cases of 47,XXY, 8 cases of 47,XXX and 6 cases of 47,XYY, with PPVs of 12.00%, 50.00%, 72.73%, and 75.00%, respectively, and false-positive rates of 0.09%, 0.02%, 0.01% and 0.01% respectively. Samples with high risk of CNV were detected in 104 cases (0.41%) and confirmed in 18 cases, with a PPV of 32.14% and a FPR of 0.15%. Samples with high risk of other chromosomal aneuploidy were detected in 34 cases (0.13%), and the diagnosis was confirmed in 3 cases, which were T2, T9, and T16 respectively. The overall PPV for other chromosome aneuploidy was 12.50%, with a FPR of 0.08%. Conclusion NIPT is indicated for trisomies 21, 18 and 13 screening, especially for T21. It also has some certain reference value for SCA and CNV, but is not recommended for screening of other chromosomal aneuploidy.

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Section: Discussionsupporting

confidence: 88%

Clinical application of noninvasive prenatal testing in the detection of fetal chromosomal diseases

Chaohong²,

Tang³

et al. 2021

Mol Cytogenet

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“…The detection e ciency of NIPT for sex chromosome aneuploidy was 12.00%, 50.00%, 72.73%, and 75.0%, respectively, which was not as effective as that for autosomal aneuploidy, and its e ciency for autosomal aneuploidy was lower than that for autosomal aneuploidy. The detection e ciency was the lowest (PPV 12.00%) for 45 XO, but moderate for 47 XXY, 47XXX, and 47 XYY (PPV 64.52%), which was consistent with that reported in the literature [12] . Because X and Y chromosomes are highly homologous, it is not easy to detect, and many fragments of the Y chromosome are similar to other chromosomes, so the accuracy of sequencing is reduced.…”

Section: Discussionsupporting

confidence: 91%

The Clinical Application of Non-invasive Prenatal Genetic Testing in the Screening of Fetal Chromosomal Diseases

Pang¹,

wang²,

Tang³

et al. 2021

Preprint

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Objective：To explore the efficacy and clinical application value of non-invasive prenatal testing (non-invasive prenatal testing, NIPT) for screening fetal chromosomal abnormalities. Methods: NIPT was performed on 25,517 pregnant women. The high-risk samples were compared with amniotic fluid and cord blood chromosome karyotype analysis. Some samples were further verified by microarray (CMA), and pregnancy outcomes were followed up. Results: Of all the cases examined, 25502 cases were detected successfully, and a total of 294 high-risk samples (1.15%) were detected, of which further diagnosis was made in 208 cases, true positive samples were detected in 96 cases, and further tests were refused in 86 cases.71 cases (0.28%) of autosomal aneuploid high-risk samples were detected and 51 cases were diagnosed, including 44 cases of trisomy 21 (T21), 5 cases of trisomy 18 (T18), and 2 cases of trisomy 13 (T13). The PPV was 90.90%, 45.45% and 33.33%, respectively. Thirteen high-risk samples of trisomy 21, 18, and 13 were detected, and 1 case was confirmed as T21 mosaic PPV was 8.33% NPV was 100%. High-risk samples of sex chromosome aneuploidy (SCA) were detected in 72 cases (0.28%), 23 cases were diagnosed, and the PPV was 40.07%. The PPV was 12.00%, 50.00%, 72.73% and 75.00%, respectively, and the PPV was 12.00%, 50.00%, 72.73% and 75.00%, respectively. High-risk samples of copy number variation (CNV) were detected in 104 cases (0.41%), and 18 cases were diagnosed, with a PPV of 32.14%. Other high-risk samples of chromosome aneuploidy were detected in 34 cases (0.13%), and 3 cases were diagnosed as T2, T9, and T16, respectively. PPV is 8.70%.Conclusion: NIPT is suitable for trisomy 21, 18, and 13 screening, especially for T21. It also has a certain reference value for SCA and microdeletion and microduplication syndromes（MMS）, and it is not recommended for screening for other chromosomal aneuploidies.

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“…There would be errors in sequencing of these locations on X and Y chromosomes because of a short sequencing length of 36 bases [19,20,22]. This may be related to a highly variable amplification of chromosome X due to lower guanosine-cytosine content and loss of X chromosome in aging women, which required further investigation [22,24,30]. Second, it can be confused by CPM, which meant the mosaicism confined only in placenta.…”

Section: Discussionmentioning

confidence: 99%

“…To our best knowledge, few studies have been published on the NIPT for screening of SCAs, and the accuracy varies among different studies [16,18,19,[22][23][24]. In this study, we aimed to investigate the screening efficiency of cfDNA for SCAs.…”

Section: Introductionmentioning

confidence: 99%

Efficiency of Noninvasive Prenatal Testing for Sex Chromosome Aneuploidies

Shi

et al. 2021

Gynecol Obstet Invest

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Objective: This study was designed to investigate the efficiency of noninvasive prenatal testing (NIPT) for screening fetal sex chromosome aneuploidies (SCAs) through sequencing of cell-free DNA in maternal plasma. Methods: This is a retrospective study on the positive NIPT results for SCAs collected from our hospital between January 2012 and December 2018. Samples with positive NIPT results for SCAs were then confirmed by prenatal or postnatal karyotyping analysis. Results: After cytogenetic analysis, abnormal karyotypes were confirmed in 104 cases and the overall positive predictive value (PPV) of NIPT for SCAs was 43.40% (102/235). The most frequently detected karyotypes included 47,XXY (n = 42), 47,XXX (n = 20), 47,XYY (n = 16), and 45,X (n = 2). Meanwhile, 10 cases were confirmed with mosaic karyotype 45,X/46,XX and 14 cases with numerical or structural chromosome abnormalities, including a double trisomy 48,XXX,+18. Cytogenetic results from the other 131 cases showed normal XX or XY, which were discordant with NIPT results. Upon analysis of parental karyotypes, 29 (12.34%) showed false positivity in NIPT results that were caused by maternal sex chromosome abnormalities. Conclusion: NIPT is an effective screening tool for SCA with a PPV of 43.40%. Maternal karyotype abnormalities occurred in 12.34% of the cases with abnormal NIPT. Diagnostic testing of the fetus and the mother are recommended.

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Clinical experience regarding the accuracy of NIPT in the detection of sex chromosome abnormality

Cited by 25 publications

References 19 publications

Clinical application of noninvasive prenatal testing in the detection of fetal chromosomal diseases

Clinical application of noninvasive prenatal testing in the detection of fetal chromosomal diseases

The Clinical Application of Non-invasive Prenatal Genetic Testing in the Screening of Fetal Chromosomal Diseases

Efficiency of Noninvasive Prenatal Testing for Sex Chromosome Aneuploidies

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