scholarly journals Expanded Noninvasive Prenatal Testing for Chromosomal aneuploidies and Copy Number Variants in a Cohort of 16128 Single Pregnancies

2021 ◽  
Author(s):  
Jing He ◽  
Xuan Feng ◽  
Xing Wang ◽  
Qinghua Zhang ◽  
Lei Zheng ◽  
...  
Keyword(s):  
Copy Number ◽  
Chromosomal Abnormalities ◽  
Copy Number Variants ◽  
Prenatal Testing ◽  
True Positive ◽  
Noninvasive Prenatal Testing ◽  
Cell Free Fetal Dna ◽  
Monogenic Diseases ◽  
Positive Rate ◽  
Chromosomal Aneuploidies

Abstract Background: Noninvasive prenatal testing (NIPT) is based on second-generation genomic sequencing technology to scan cell-free fetal DNA originating from the placenta in maternal plasma. As the depth of sequencing increases, it can be used to focus on chromosomal aneuploidies, copy number variants (CNVs), and monogenic diseases. It can significantly improve the accuracy of prenatal screening and reduces the number of invasive testing.Methods: In this study, we retrospectively analyzed 16128 naturally conceived singleton pregnancies who underwent expanded NIPT to calculate the true positive rate (TPR) of chromosomal aneuploidies and CNVs, and analyzed the potential influence of maternal sex chromosome abnormalities (SCAs) and maternal CNVs on expanded NIPT results.Results: After invasive prenatal diagnosis and follow-up, 103 pregnancies were found to be true-positive, including 73 cases of chromosomal abnormalities and 30 cases of CNVs. The TPR of T21 was 84.62%, T18 was 50.00%, T13 was 22.22%, SCA was 34.06%, and CNVs was 40.28%. In addition, we found that the positive rate of aneuploidies increased with maternal age and that maternal SCAs accounted for 13.33% of the 60 false positive cases of SCAs.Conclusion: Expanded NIPT showed high sensitivity and specificity in detecting diseases of chromosomal abnormalities. It also shows good performance in detecting CNVs, but maternal SCAs and CNVs confused some NIPT results, indicating it is still necessary to study the potential maternal influence on expanded NIPT results and to report related clinical validation studies.

scholarly journals Validation of Copy Number Variants Detection from Pregnant Plasma Using Low-Pass Whole-Genome Sequencing in Noninvasive Prenatal Testing-Like Settings

Diagnostics ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 569
Author(s):  
Michaela Hyblova ◽  
Maria Harsanyova ◽  
Diana Nikulenkov-Grochova ◽  
Jitka Kadlecova ◽  
Marcel Kucharik ◽  
...  
Keyword(s):  
Copy Number ◽  
Copy Number Variants ◽  
Prenatal Testing ◽  
Detection Algorithm ◽  
Detection Sensitivity ◽  
Clinical Settings ◽  
Noninvasive Prenatal Testing ◽  
Low Pass ◽  
Cnv Detection ◽  
Fetal Fraction

Detection of copy number variants as an integral part of noninvasive prenatal testing is increasingly used in clinical practice worldwide. We performed validation on plasma samples from 34 pregnant women with known aberrations using cell-free DNA sequencing to evaluate the sensitivity for copy number variants (CNV) detection using an in-house CNV fraction-based detection algorithm. The sensitivity for CNVs smaller than 3 megabases (Mb), larger than 3Mb, and overall was 78.57%, 100%, and 90.6%, respectively. Regarding the fetal fraction, detection sensitivity in the group with a fetal fraction of less than 10% was 57.14%, whereas there was 100% sensitivity in the group with fetal fraction exceeding 10%. The assay is also capable of indicating whether the origin of an aberration is exclusively fetal or fetomaternal/maternal. This validation demonstrated that a CNV fraction-based algorithm was applicable and feasible in clinical settings as a supplement to testing for common trisomies 21, 18, and 13.

scholarly journals Cell-free DNA screening for sex chromosomal aneuploidies in 9985 pregnancies: Italian single experience.

2020 ◽  
Author(s):  
Katia Margiotti ◽  
Anthony Cesta ◽  
Claudio Dello Russo ◽  
Antonella Cima ◽  
Maria Antonietta Barone Barone ◽  
...  
Keyword(s):  
Test Performance ◽  
Sex Chromosome ◽  
Clinical Performance ◽  
Prenatal Testing ◽  
Potential Method ◽  
True Positive ◽  
Noninvasive Prenatal Testing ◽  
Fetal Dna ◽  
Cell Free Fetal Dna ◽  
Next Generation Sequencing Ngs

Abstract Objective : Noninvasive prenatal testing (NIPT) using cell-free fetal DNA (cffDNA) has been widely accepted in recent years to detect common fetal autosomal chromosome aneuploidies and sex chromosome aneuploidies (SCAs). In this study, the clinical performance of our fetal DNA testing was investigated by analyzing the sex chromosome aneuploidy aberrations among 9985 pregnancies. The study was a retrospective analysis of collected NIPT data from the Ion S5 Next-Generation Sequencing (NGS) platform obtained from Altamedica Medical Centre of Rome. Results : NIPT analysis of 9985 pregnancies revealed 31 cases with abnormal SCA results (0.31%). Among the 31 positive NIPT cases, 22 women agreed to undergo fetal karyotyping, whereas 9 refused further analyses. Of the 22 women verified by karyotyping analysis, 77.3% (17/22) were confirmed to be true positive SCAs, whereas 22.7% (5/22) were false positive. Among the true positive cases, 53.0% (9/17) were positive for monosomy X, 17.6% (3/17) were positive for 47,XXX aneuploidy, 23.5% (4/17) were positive for 47,XXY aneuploidy, and 5.9% (1/17) were positive for 47,XYY aneuploidy. In conclusion, the present results confirm that NIPT is a potential method for SCA screening, although this technology needs to be further investigated to improve the test performance.

scholarly journals PREIMPLANTATION GENETIC TESTING: Non-invasive prenatal testing for aneuploidy, copy-number variants and single-gene disorders

Reproduction ◽  
2020 ◽  
Vol 160 (5) ◽  
pp. A1-A11
Author(s):  
J Shaw ◽  
E Scotchman ◽  
N Chandler ◽  
L S Chitty
Keyword(s):  
Copy Number ◽  
Sex Chromosome ◽  
Single Gene ◽  
Copy Number Variants ◽  
Prenatal Testing ◽  
Aneuploidy Screening ◽  
Preimplantation Genetic Testing ◽  
Non Invasive ◽  
Single Gene Disorders ◽  
Cell Free Fetal Dna

The discovery of cell-free fetal DNA (cffDNA) in maternal plasma has enabled a paradigm shift in prenatal testing, allowing for safer, earlier detection of genetic conditions of the fetus. Non-invasive prenatal testing (NIPT) for fetal aneuploidies has provided an alternative, highly efficient approach to first-trimester aneuploidy screening, and since its inception has been rapidly adopted worldwide. Due to the genome-wide nature of some NIPT protocols, the commercial sector has widened the scope of cell-free DNA (cfDNA) screening to include sex chromosome aneuploidies, rare autosomal trisomies and sub-microscopic copy-number variants. These developments may be marketed as ‘expanded NIPT’ or ‘NIPT Plus’ and bring with them a plethora of ethical and practical considerations. Concurrently, cfDNA tests for single-gene disorders, termed non-invasive prenatal diagnosis (NIPD), have been developed for an increasing array of conditions but are less widely available. Despite the fact that all these tests utilise the same biomarker, cfDNA, there is considerable variation in key parameters such as sensitivity, specificity and positive predictive value depending on what the test is for. The distinction between diagnostics and screening has become blurred, and there is a clear need for the education of physicians and patients regarding the technical capabilities and limitations of these different forms of testing. Furthermore, there is a requirement for consistent guidelines that apply across health sectors, both public and commercial, to ensure that tests are validated and robust and that careful and appropriate pre-test and post-test counselling is provided by professionals who understand the tests offered.

scholarly journals Expanded noninvasive prenatal testing for fetal aneuploidy and copy number variations and parental willingness for invasive diagnosis in a cohort of 18,516 cases

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Yunsheng Ge ◽  
Jia Li ◽  
Jianlong Zhuang ◽  
Jian Zhang ◽  
Yanru Huang ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
High Risk ◽  
Pregnant Women ◽  
Copy Number ◽  
Prenatal Testing ◽  
Copy Number Variations ◽  
Trisomy 13 ◽  
Noninvasive Prenatal Testing ◽  
Predictive Values ◽  
Parental Willingness

Abstract Background Noninvasive prenatal testing (NIPT) has been wildly used to screen for common aneuplodies. In recent years, the test has been expanded to detect rare autosomal aneuploidies (RATs) and copy number variations (CNVs). This study was performed to investigate the performance of expanded noninvasive prenatal testing (expanded NIPT) in screening for common trisomies, sex chromosomal aneuploidies (SCAs), rare autosomal aneuploidies (RATs), and copy number variations (CNVs) and parental willingness for invasive prenatal diagnosis in a Chinese prenatal diagnosis center. Methods A total of 24,702 pregnant women were retrospectively analyzed at the Women and Children’s Hospital from January 2013 to April 2019, among which expanded NIPT had been successfully conducted in 24,702 pregnant women. The high-risk expanded NIPT results were validated by karyotype analysis and chromosomal microarray analysis. All the tested pregnant women were followed up for pregnancy outcomes. Results Of the 24,702 cases, successful follow-up was conducted in 98.77% (401/446) of cases with common trisomies and SCAs, 91.95% (80/87) of RAT and CNV cases, and 76.25% (18,429/24,169) of cases with low-risk screening results. The sensitivity of expanded NIPT was 100% (95% confidence interval[CI], 97.38–100%), 96.67%(95%CI, 82.78–99.92%), and 100%(95%CI, 66.37–100.00%), and the specificity was 99.92%(95%CI, 99.87–99.96%), 99.96%(95%CI, 99.91–99.98%), and 99.88% (95%CI, 99.82–99.93%) for the detection of trisomies 21, 18, and 13, respectively. Expanded NIPT detected 45,X, 47,XXX, 47,XXY, XYY syndrome, RATs, and CNVs with positive predictive values of 25.49%, 75%, 94.12%, 76.19%, 6.45%, and 50%, respectively. The women carrying fetuses with Trisomy 21/Trisomy 18/Trisomy 13 underwent invasive prenatal diagnosis and terminated their pregnancies at higher rates than those at high risk for SCAs, RATs, and CNVs. Conclusions Our study demonstrates that the expanded NIPT detects fetal trisomies 21, 18, and 13 with high sensitivity and specificity. The accuracy of detecting SCAs, RATs, and CNVs is still relatively poor and needs to be improved. With a high-risk expanded NIPT result, the women at high risk for common trisomies are more likely to undergo invasive prenatal diagnosis procedures and terminate their pregnancies than those with unusual chromosome abnormalities.

Noninvasive Prenatal Testing for Whole Fetal Chromosomal Aneuploidies: A Multicenter Prospective Cohort Trial in Taiwan

2013 ◽  
Vol 35 (1) ◽  
pp. 13-17 ◽  
Author(s):  
S.W. Steven Shaw ◽  
Ching-Hua Hsiao ◽  
Chih-Yao Chen ◽  
Yuanyuan Ren ◽  
Feng Tian ◽  
...  
Keyword(s):  
Prospective Cohort ◽  
Prenatal Testing ◽  
Noninvasive Prenatal Testing ◽  
Chromosomal Aneuploidies ◽  
Multicenter Prospective Cohort

Non-Invasive Testing, Non-Invasive Counseling

2015 ◽  
Vol 43 (2) ◽  
pp. 228-240 ◽  
Author(s):  
Rachel Rebouché
Keyword(s):  
Chromosomal Abnormalities ◽  
Genetic Test ◽  
Prenatal Testing ◽  
Private Companies ◽  
Major Health ◽  
Prenatal Health ◽  
Non Invasive ◽  
Fetal Dna ◽  
Cell Free Fetal Dna ◽  
A Company

A regulatory moment for prenatal health care is here. An increasing amount of legislative attention has concentrated on the decisions pregnant women make after prenatal testing. The impetus for this legislation is a new non-invasive prenatal genetic test (NIPT). From the beginning of pregnancy, cell-free fetal DNA travels across the placental lining into the mother’s bloodstream, increasing in quantity as the pregnancy progresses. Laboratories can now analyze that DNA for chromosomal abnormalities and for fetal sex at 10 weeks of gestation. NIPT, which relies on a sample of the pregnant woman’s blood, is painless, occurs early in pregnancy, and is available for clinical and commercial use. In 2013, major health insurance plans began to cover NIPT for certain populations of women, such as women over 35 years old. And private companies have started marketing prenatal testing kits directly to consumers, who return a blood sample from the prospective mother to a company laboratory.

Noninvasive Prenatal Testing Using Cell‐Free Fetal DNA in Maternal Plasma

2015 ◽  
Vol 84 (1) ◽  
Author(s):  
Nilesh Dharajiya ◽  
Tricia Zwiefelhofer ◽  
Xiaojun Guan ◽  
Vach Angkachatchai ◽  
Juan‐Sebastian Saldivar
Keyword(s):  
Prenatal Testing ◽  
Maternal Plasma ◽  
Noninvasive Prenatal Testing ◽  
Fetal Dna ◽  
Cell Free Fetal Dna

scholarly journals Noninvasive prenatal testing for chromosome aneuploidies and subchromosomal microdeletions/microduplications in a cohort of 42,910 single pregnancies with different clinical features

2019 ◽  
Vol 13 (1) ◽  
Author(s):  
Yibo Chen ◽  
Qi Yu ◽  
Xiongying Mao ◽  
Wei Lei ◽  
Miaonan He ◽  
...  
Keyword(s):  
Clinical Features ◽  
Sex Chromosome ◽  
Prenatal Testing ◽  
Maternal Plasma ◽  
Trisomy 13 ◽  
Noninvasive Prenatal Testing ◽  
Detection Rates ◽  
Non Invasive ◽  
Cell Free Fetal Dna ◽  
Sex Chromosome Aneuploidies

Abstract Background Since the discovery of cell-free DNA (cfDNA) in maternal plasma, it has opened up new approaches for non-invasive prenatal testing. With the development of whole-genome sequencing, small subchromosomal deletions and duplications could be found by NIPT. This study is to review the efficacy of NIPT as a screening test for aneuploidies and CNVs in 42,910 single pregnancies. Methods A total of 42,910 single pregnancies with different clinical features were recruited. The cell-free fetal DNA was directly sequenced. Each of the chromosome aneuploidies and the subchromosomal microdeletions/microduplications of PPV were analyzed. Results A total of 534 pregnancies (1.24%) were abnormal results detected by NIPT, and 403 pregnancies had underwent prenatal diagnosis. The positive predictive value (PPV) for trisomy 21(T21), trisomy 18 (T18), trisomy 13 (T13), sex chromosome aneuploidies (SCAs), and other chromosome aneuploidy was 79.23%, 54.84%, 13.79%, 33.04%, and 9.38% respectively. The PPV for CNVs was 28.99%. The PPV for CNVs ≤ 5 Mb is 20.83%, for within 5–10 Mb 50.00%, for > 10 Mb 27.27% respectively. PPVs of NIPT according to pregnancies characteristics are also different. Conclusion Our data have potential significance in demonstrating the usefulness of NIPT profiling not only for common whole chromosome aneuploidies but also for CNVs. However, this newest method is still in its infancy for CNVs. There is still a need for clinical validation studies with accurate detection rates and false positive rates in clinical practice.

scholarly journals Cell-free fetal DNA-based noninvasive prenatal testing of aneuploidy

2017 ◽  
Vol 19 (3) ◽  
pp. 211-218 ◽  
Author(s):  
Fiona L Mackie ◽  
Stephanie Allen ◽  
R Katie Morris ◽  
Mark D Kilby
Keyword(s):  
Prenatal Testing ◽  
Noninvasive Prenatal Testing ◽  
Fetal Dna ◽  
Cell Free Fetal Dna
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