The application of expanded noninvasive prenatal screening for genome-wide chromosomal abnormalities and genetic counseling

Chen, Yun; Lai, Yunli; Xu, Fuben; Qin, Haisong; Tang, Yanqing; Huang, Xuejun; Meng, Lintao; Su, Jiasun; Sun, Weijia; Shen, Yiping; Wei, Hongwei

doi:10.1080/14767058.2021.1907333

Cited by 21 publications

(27 citation statements)

References 34 publications

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“…Many investigations indicated that NIPT‐plus was available to detect fetal chromosome CNVs (Chen et al, 2021; Kaseniit et al, 2018; Liang et al, 2019b; Wapner et al, 2015). The research of Helgeson et al confirmed that NIPT‐plus can reach a higher PPV of 60% ~ 100% via optimized bioinformatics algorithms for detecting CNVs (Helgeson et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Clinical application of expanded noninvasive prenatal testing for fetal chromosome abnormalities in a cohort of 39,580 pregnancies

Chen

Zhang

et al. 2022

American J of Med Genetics Pt A

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The aim of this study was to determine the predictive value of expanded noninvasive prenatal testing (NIPT‐plus) for fetal chromosome abnormalities in the second trimester (12–26 weeks). We conducted a retrospective cohort study of 39,580 pregnancies with NIPT‐plus. Screening positive cases were diagnosed with karyotyping and single‐nucleotide polymorphism array analysis (SNP array)/copy number variation sequencing (CNV‐seq) with follow‐up. The positive predictive values (PPVs) of trisomy 21, 18, and 13 (T21, T18, and T13), sex chromosome aneuploidies (SCAs), and microdeletion and microduplication syndromes (MMS) by NIPT‐plus were recorded. We assessed the predictive value of NIPT‐plus based on maternal age and conventional indications. Of 39,580 pregnancies with NIPT‐plus, 511 (1.3%) had prenatal screening positive results of fetal chromosome abnormality, of which 87.7% (448/511) had invasive prenatal diagnosis. NIPT‐plus performed better in predicting fetal SCAs and chromosome aneuploidies for pregnancies with advanced maternal age (AMA) than young maternal age (YMA). Besides, the PPVs of T21, T13, and chromosome aneuploidies showed an upward trend when comparison was based on maternal age in 5‐year subintervals. The termination rates of 45,X, 47,XXX, 47,XXY, and 47,XYY were 100% (11/11), 20.0% (3/15), 91.7% (22/24), and 7.1% (1/14) with postnatal follow‐up. Last but not least, the PPV for MMS is 41.7% (30/72), which may have a positive correlation between the size of CNVs. Pregnant women with screen‐positive results for common trisomies (T13, T18, and T21) were more willing to conduct invasive prenatal diagnosis compared to those with positive results for SCAs or MMS. However, the current study demonstrated SCAs and MMS had the lowest PPV. This highlights the importance of confirmatory prenatal diagnosis in those patients and the potential impact on genetic counseling and informative decision‐making.

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Section: Discussionmentioning

confidence: 99%

Clinical application of expanded noninvasive prenatal testing for fetal chromosome abnormalities in a cohort of 39,580 pregnancies

Chen

Zhang

et al. 2022

American J of Med Genetics Pt A

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“…Twelve studies solely evaluated the genome-wide detection of CNVs. Most of them screened for previously undiagnosed fetal CNVs [ 4 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 ], but two studies obtained samples with known CNVs and retrospectively conducted NIPT analysis [ 39 , 40 ].…”

Section: Resultsmentioning

confidence: 99%

“…Most of the studies obtained plasma samples from the population of pregnant women who underwent NIPT without specifically defining referral indications for the screening [ 4 , 10 , 15 , 17 , 19 , 20 , 21 , 28 , 30 , 31 , 33 , 34 , 35 , 37 , 38 ]. Some included only samples of women with high-risk pregnancies (over 35 years of age), positive serum screening results, a history of aneuploidy, abnormal ultrasound findings, or simply maternal anxiety [ 22 , 32 , 40 ].…”

Section: Resultsmentioning

confidence: 99%

Validity and Utility of Non-Invasive Prenatal Testing for Copy Number Variations and Microdeletions: A Systematic Review

Zaninović

Bašković

Ježek

et al. 2022

JCM

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Valid data on prenatal cell-free DNA-based screening tests for copy number variations and microdeletions are still insufficient. We aimed to compare different methodological approaches concerning the achieved diagnostic accuracy measurements and positive predictive values. For this systematic review, we searched the Scopus and PubMed databases and backward citations for studies published between 2013 and 4 February 2022 and included articles reporting the analytical and clinical performance of cfDNA screening tests for CNVs and microdeletions. Of the 1810 articles identified, 32 met the criteria. The reported sensitivity of the applied tests ranged from 20% to 100%, the specificity from 81.62% to 100%, and the PPV from 3% to 100% for cases with diagnostic or clinical follow-up information. No confirmatory analysis was available in the majority of cases with negative screening results, and, therefore, the NPVs could not be determined. NIPT for CNVs and microdeletions should be used with caution and any developments regarding new technologies should undergo strict evaluation before their implementation into clinical practice. Indications for testing should be in correlation with the application guidelines issued by international organizations in the field of prenatal diagnostics.

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“…NIPT also is utilized to screen for select microdeletions/microduplications and other rare autosomal trisomies but shows relatively poor positive predictive value (PPV) for these applications (6,7).…”

Section: Introductionmentioning

confidence: 99%

“…CMA has become a first-tier diagnostic test at greater frequency across the globe, particularly when fetal anomalies are encountered. However, KT, FISH, MLPA and qPCR remain the tests of choice in many countries, primarily owing to financial and resource constraints (6,7,9,12).…”

Section: Introductionmentioning

confidence: 99%

Multisite evaluation and validation of Optical Genome Mapping for prenatal genetic testing

Stevenson¹,

Liu

Iqbal

et al. 2022

Preprint

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Cytogenetic studies represent a critical component of prenatal genetic testing. Prenatal diagnostic testing of amniotic fluid, chorionic villus sampling, or more rarely, fetal cord blood, is recommended following a positive or unreportable NIPT, maternal serum screen, abnormal ultrasound or increased genetic risk based on family history. While chromosomal microarray is the recommended first-tier prenatal diagnostic test for the detection of sub-microscopic copy number variants, in practice, multiple assays are often assessed, in concert, to achieve a final diagnostic result. The use of multiple methodologies is costly, time consuming, and labor intensive. Optical genome mapping is an emerging technique with application for prenatal diagnosis because of its ability to detect and resolve, in a single assay, all classes of pathogenic cytogenetic aberrations detectable by karyotyping, FISH, and microarray. In an effort to characterize the potential of optical genome mapping as a novel alternative to conventional testing, a multi-site, multi-operator, multi-instrument clinical research study was conducted to demonstrate its analytic validity and clinical utility. In the first phase a total of 200 specimens representing 123 unique cases demonstrated 100% concordance with standard of care methods and 100% reproducibility between sites, operators, and instruments. Analysis and interpretation of cases with incidental findings of potential clinical significance also were performed.

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The application of expanded noninvasive prenatal screening for genome-wide chromosomal abnormalities and genetic counseling

Cited by 21 publications

References 34 publications

Clinical application of expanded noninvasive prenatal testing for fetal chromosome abnormalities in a cohort of 39,580 pregnancies

Clinical application of expanded noninvasive prenatal testing for fetal chromosome abnormalities in a cohort of 39,580 pregnancies

Validity and Utility of Non-Invasive Prenatal Testing for Copy Number Variations and Microdeletions: A Systematic Review

Multisite evaluation and validation of Optical Genome Mapping for prenatal genetic testing

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