Clinical Experience with Genome-Wide Noninvasive Prenatal Screening in a Large Cohort of Twin Pregnancies.
De Falco L, Savarese G, Savarese P, et al. Genes (Basel). 2023;14(5):982. Published 2023 Apr 26. doi:10.3390/genes14050982. Open Access: Learn more
Tags: Laboratory Performance / Laboratory Experience, 2023, Italy, RAAs, CNVs
- Cohort of 1,244 twin pregnancy samples undergoing NIPT, of which 61.5% chose GW-NIPT for RAAs and CNVs in addition to common trisomies.
- There were 29 high-risk results: 18 T21, one T18, 6 RAA, and 4 CNV cases. Clinical and diagnostic follow-up was available for 27/29 (93%) of these cases.
- Clinical follow-up was available for 96.6% of low-risk cases; all were true negatives.
Laboratory performance of genome-wide cfDNA for copy number variants as compared to prenatal microarray.
Soster E, Tynan J, Gibbons C, et al. Mol Cytogenet. 2023;16(1):10. Published 2023 Jun 10. doi:10.1186/s13039-023-00642-4 Open Access: Learn more
Tags: Laboratory Performance / Laboratory Experience, 2023, United States, CNVs
- Reviewed 701 high-risk pregnancies with both GW-NIPT and prenatal microarray.
- For aneuploidies, CNVs ≥7Mb, and select microdeletions, sensitivity was 93.8%, specificity was 97.3%, and PPV was 63.8%.
- “Conclusions: While microarray provides the most robust assessment of fetal CNVs, this study suggests that genome wide cfDNA can reliably screen for large CNVs in a high-risk cohort. Informed consent and adequate pretest counseling are essential to ensuring patients understand the benefits and limitations of all prenatal testing and screening options.”
Positive predictive value estimates for noninvasive prenatal testing from data of a prenatal diagnosis laboratory and literature review.
Liu S, Yang F, Chang Q, et al. Mol Cytogenet. 2022;15(1):29. Published 2022 Jul 6. doi:10.1186/s13039-022-00607-z. Open Access: Learn more
Tags: Laboratory Performance / Laboratory Experience, 2022, China, RAAs, CNVs
- Retrospective study of women referred for invasive prenatal diagnosis following a positive NIPT results.
- PPVs for trisomies 21, 18, and 13 were 86.1%, 57.8%, and 25.0%, respectively.
- PPVs for rare chromosomal abnormalities and and CNVs were 17.0% and 40.4%, respectively.
- A significant increase in true positives was seen in the high-risk groups compared to low- and moderate-risk groups.
Positive predictive values and outcomes for uninformative cell-free DNA tests: An Italian multicentric Cytogenetic and cytogenomic Audit of diagnOstic testing (ICARO study).
Grati FR, Bestetti I, De Siero D, et al.. Prenat Diagn. 2022;42(13):1575-1586. doi:10.1002/pd.6271.
Tags: Laboratory Performance / Laboratory Experience, 2022, Italy, RAAs
- “Diagnostic test results were collected for 1327 women with a positive NIPT. The highest PPVs were for Trisomy (T) 21 (624/671, 93%) and XYY (26/27, 96.3%), while rare autosomal trisomies (9/47, 19.1%) and recurrent microdeletions (8/55, 14.5%) had the lowest PPVs.”
- Prenatal diagnostic test results were collected by Italian laboratories between 2013 and March 2020 for 1327 women.
- PPV for RATs was 19.1% (9/47). PPV for segmental imbalances >7 Mb was 24.1% (7/29).
Expanding the Scope of Non-invasive Prenatal Testing to Detect Fetal Chromosomal Copy Number Variations.
Chen S, Zhang L, Gao J, et al. Front Mol Biosci. 2021;8:649169. Published 2021 May 12. doi:10.3389/fmolb.2021.649169. Open Access: Learn more
Tags: Laboratory Performance / Laboratory Experience, 2021, China, CNVs
- Analyzed the NIPT screen positive rate at different read depths and identified a strategy for fetal CNV detection.
- “Increasing read depth in NGS [next-generation sequencing] improves the positive CNV detection rate while lowering the false positive detection rate. NIPT by NGS may be an accurate method of fetal chromosome analysis and reduce the rate of birth defects.”
Performance of a Paired-End Sequencing-Based Noninvasive Prenatal Screening Test in the Detection of Genome-Wide Fetal Chromosomal Anomalies.
Pertile MD, Flowers N, Vavrek D, et al. Clin Chem. 2021;67(9):1210-1219. doi:10.1093/clinchem/hvab067. Open Access: Learn more
Tags: Laboratory Experience / Laboratory Performance, 2021, Australia, RAAs, CNVs
- Study of GW-NIPT in 2335 frozen plasma samples to detect GW chromosomal anomalies including common trisomies, SCAs, RAAs, and partial deletions and duplications.
- “Genome-wide screening analysis including known mosaics correctly classified 27/28 RAAs and 20/27 partial deletions/duplications with a specificity of 99.80% for both anomalies, and an overall genome-wide specificity for all anomalies of 99.34%.”
- ”With an overall genome-wide clinical specificity for any anomaly of 99.34%, this genome-wide screen allows for detection of a broad range of chromosomal anomalies while retaining a clinical specificity far superior to the ~5% false-positive rate of serum screening.”
Genome-wide cell-free DNA screening: a focus on copy-number variants
Rafalko J, Soster E, Caldwell S, et al. Genet Med. 2021;23(10):1847-1853. doi:10.1038/s41436-021-01227-5. Open Access: Learn more
Tags: Laboratory Performance / Laboratory Experience, 2021, United States, CNVs
- In a cohort of 86,902 Expanded NIPT samples, this publication focuses on the 490 (0.56%) cases that were screen positive for at least 1 subchromosomal partial deletion/duplication. Diagnostic outcomes were available in 50% of these cases, in which the PPV was found to be greater than 70%.
Three years of clinical experience with a genome-wide cfDNA screening test for aneuploidies and copy-number variants
[published correction appears in Genet Med. 2021 May 6;:]. Soster E, Boomer T, Hicks S, et al. Genet Med. 2021;23(7):1349-1355. doi:10.1038/s41436-021-01135-8. Open Access: Learn more
Tags: Laboratory Performance / Laboratory Experience, Clinical Experience / Clinical Utility, 2021, United States, RAAs, CNVs
- This publication is a retrospective analysis of over 55,000 samples submitted for Expanded NIPT to the laboratory, with diagnostic outcomes available in over 40% of screen positive cases. The publication reports on testing indications, demographics, results, and performance. The authors noted that indications shifted during the 3-year period, with a decrease in referrals for ‘ultrasound findings’ (22.0% to 12.0%) and an increase in referrals of ‘no known high-risk indication’ (3.0% to 16.6%). Of the screen positive results, they reported that 25% would have been missed with NIPT limited to the common aneuploidies. They concluded that, although a broader patient population is using Expanded NIPT, the positivity rates and genome-wide events have remained stable at approximately 5% and 25%, respectively.
Strategy for Use of Genome-Wide Non-Invasive Prenatal Testing for Rare Autosomal Aneuploidies and Unbalanced Structural Chromosomal Anomalies
Kleinfinger P, Lohmann L, Luscan A, et al. J Clin Med. 2020;9(8):2466. Published 2020 Aug 1. doi:10.3390/jcm9082466. Open Access: Learn more
Tags: Laboratory Performance / Laboratory Experience, 2020, France, RAAs, CNVs
- This publication recognizes that fetal chromosome anomalies beyond the common aneuploidies occur more frequently than previously thought and subsequently can impact fetal development. As such, the authors propose a screening strategy for Expanded NIPT to detect chromosome anomalies beyond the common trisomies. Results showed that Expanded NIPT can screen for rare autosomal aneuploidies and partial deletions/duplications with an acceptable sensitivity and a small increase in the rate of invasive testing.
Noninvasive prenatal testing for fetal subchromosomal copy number variations and chromosomal aneuploidy by low-pass whole-genome sequencing
Yu D, Zhang K, Han M, et al. Mol Genet Genomic Med. 2019;7(6):e674. doi:10.1002/mgg3.674. Open Access: Learn more
Tags: Laboratory Performance / Laboratory Experience, 2019, China, RAAs, CNVs
- This publication reports on the development and evaluation of a low-pass whole genome sequencing assay for the detection of fetal CNVs and chromosomal aneuploidies in 20,003 pregnant women.