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.

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

scholarly journals The Level of Free Fetal DNA as Precise Noninvasive Marker for Chromosomal Aneuploidies: First Results from BALTIC Region

Medicina ◽  
2020 ◽  
Vol 56 (11) ◽  
pp. 579
Author(s):  
Danielius Serapinas ◽  
Evelina Boreikaitė ◽  
Agnė Bartkevičiūtė ◽  
Kristina Norvilaitė ◽  
Andrius Narbekovas ◽  
...  
Keyword(s):  
Sex Chromosome ◽  
Prenatal Testing ◽  
Maternal Blood ◽  
Singleton Pregnancy ◽  
Fetal Dna ◽  
Sex Chromosome Abnormalities ◽  
Cell Free Fetal Dna ◽  
Xyy Syndrome ◽  
First Results ◽  
Fetal Fraction

Background and objectives: Noninvasive prenatal testing (NIPT), which has been introduced clinically since 2011, uses the circulating cell-free fetal DNA in the maternal blood to evaluate the risk of a chromosomal anomaly. The aim of this study was to examine the effectiveness of NIPT using a single nucleotide polymorphism method. Materials and Methods: A retrospective study was conducted between 2013 and 2019. The Natera Panorama test was used to analyze the risk of trisomies 21, 18, 13, X monosomy, trisomy, and other sex chromosome abnormalities. A positive result of NIPT for aneuploidy was confirmed by invasive testing. Results: 850 women with a singleton pregnancy participated in the study. The median fetal fraction was 9.0%. The fetal fraction was lower in the no-call group (3.1%) compared with the group that received a call (9.1%) (p < 0.001). A positive correlation was determined between the gestational age and the fetal fraction (r = 0.180, p < 0.001). The overall positive predictive value (PPV) of NIPT for trisomy 21 (n = 9), trisomy 18 (n = 3) and XYY syndrome (n = 1) was 100%. Conclusions: The results of present study showed 100% PPV effectiveness of NIPT Panorama test detecting trisomies of 21 and 18 chromosomes, as well as XYY syndrome in the studied cohort. Therefore, NIPT due to its high PPV, significantly reduces the need for invasive testing, thereby reducing the risk of miscarriage and stillbirth.

Factors affecting levels of circulating cell-free fetal DNA in maternal plasma and their implications for noninvasive prenatal testing

2015 ◽  
Vol 35 (8) ◽  
pp. 816-822 ◽  
Author(s):  
Sarah L. Kinnings ◽  
Jennifer A. Geis ◽  
Eyad Almasri ◽  
Huiquan Wang ◽  
Xiaojun Guan ◽  
...  
Keyword(s):  
Prenatal Testing ◽  
Maternal Plasma ◽  
Noninvasive Prenatal Testing ◽  
Factors Affecting ◽  
Fetal Dna ◽  
Cell Free Fetal Dna

scholarly journals Clinical performance of Non-invasive prenatal testing for sex chromosomal aneuploidies in Northeast China

2020 ◽  
Author(s):  
Lu Wang ◽  
Rulin Dai ◽  
Qingyang Shi ◽  
Yuting Jiang ◽  
Hongguo Zhang ◽  
...  
Keyword(s):  
False Positive ◽  
Northeast China ◽  
Sex Chromosome ◽  
Clinical Performance ◽  
False Positive Rate ◽  
False Negative ◽  
Prenatal Testing ◽  
Potential Method ◽  
Sequencing Platform ◽  
Non Invasive

Abstract Background: Along with the discovery of cell-free DNA (cfDNA) and the invention of next-generation sequencing (NGS), non-invasive prenatal testing (NIPT) had appeared and been applied for detecting common aneuploidies such as trisomy 21, 18, and 13, with low false-negative and false-positive rates. Recently, it had also been used for sex chromosome aneuploidies (SCAs). To assess the clinical utility of NIPT for SCAs in Northeast China, we collected NIPT data from BGI 500 sequencing platform in the Center for Reproductive Medicine, Center for Prenatal Diagnosis of the First Hospital of Jilin University, and calculate the positive predictive value (PPV) and false positive rate (FPR). Results: A cohort of 14936 samples were analyzed by NIPT, and revealed 70 cases with SCAs high-risk, among them, 40 women agreed to undergo amniocentesis, but as many as 30 ones refused further diagnose. Based on verified fetal karyotype, 30.0% (12/40) were confirmed to be a true positive. Unluckily, the PPV for monosomy X performed 0%. Besides, positive 47,XXX were 46.67% (7/15), 40.00% (2/5) were positive for 47, XYY, and 42.86% (3/7) were positive for 47, XXY.Conclusions: In conclusion, our present results confirmed that NIPT sequenced by BGI 500 demonstrated lowest PPVs for 45,X, but the more accurate prediction for other SCAs, it is still a potential method for SCAs screening. Henceforth, we should focus on how to improve the test utility and provide better services for pregnant women in need.

scholarly journals Cell-free fetal DNA testing and its correlation with prenatal indications

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jing-wei Wang ◽  
Yong-nan Lyu ◽  
Bin Qiao ◽  
Yan Li ◽  
Yan Zhang ◽  
...  
Keyword(s):  
Prenatal Screening ◽  
Sex Chromosome ◽  
Prenatal Testing ◽  
High Sensitivity ◽  
Nuchal Translucency ◽  
Fetal Dna ◽  
Sex Chromosome Abnormalities ◽  
Autosomal Aneuploidy ◽  
Cell Free Fetal Dna ◽  
Positive Rate

Abstract Background The prenatal test of cell-free fetal DNA (cffDNA) is also known as noninvasive prenatal testing (NIPT) with high sensitivity and specificity. This study is to evaluate the performance of NIPT and its clinical relevance with various clinical indications. Methods A retrospective analysis was conducted on 14,316 pregnant women with prenatal indications, including advanced maternal age (≥35 years), maternal serum screening abnormalities, the thickened nuchal translucency (≥2.5 mm) and other ultrasound abnormalities, twin pregnancy/IVF-ET pregnancy, etc. The whole-genome sequencing (WGS) of maternal plasma cffDNA was employed in this study. Results A total of 189 (1.32%) positive NIPT cases were identified, and 113/189 (59.79%)cases were confirmed by invasive prenatal testing. Abnormal serological screening (53.14%) was the most common indication, followed by elderly pregnancy (23.02%). The positive prediction value for T21, T18, T13, sex chromosome abnormalities, other autosomal aneuploidy abnormalities, and CNV abnormalities were 91.84, 68.75,37.50, 66.67, 14.29, and 6.45%, respectively. The positive rate and the true positive rate of nuchal translucency (NT) thickening were the highest (4.17 and 3.33%), followed by the voluntary requirement group (3.49 and 1.90%) in the various prenatal screening indications. The cffDNA concentration was linearly correlated with gestational age (≥10 weeks) and the positive NIPT group’s Z-score values. Conclusions whole-genome sequencing of cffDNA has extremely high sensitivity and specificity for T21, high sensitivity for T18, sex chromosome abnormalities, and T13. It also provides evidence for other abnormal chromosomal karyotypes (CNV and non-21/18/13 autosomal aneuploidy abnormalities). The cffDNA concentration is closely related to the gestational age and determines the specificity of NIPT. Our results highlight NIPT’s clinical significance, which is an effective prenatal screening tool for high-quality care of pregnancy.

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 Clinical Performance of Non-Invasive Prenatal Testing for Sex Chromosomal Aneuploidies in Northeast China

2020 ◽  
Author(s):  
Lu Wang ◽  
Rulin Dai ◽  
Qingyang Shi ◽  
Yuting Jiang ◽  
Hongguo Zhang ◽  
...  
Keyword(s):  
False Positive ◽  
Northeast China ◽  
Sex Chromosome ◽  
Clinical Performance ◽  
False Positive Rate ◽  
False Negative ◽  
Prenatal Testing ◽  
Potential Method ◽  
Sequencing Platform ◽  
Non Invasive

Abstract Background: Along with the discovery of cell-free DNA (cfDNA) and the invention of next-generation sequencing (NGS), non-invasive prenatal testing (NIPT) had appeared and been applied for detecting common aneuploidies such as trisomy 21, 18, and 13, with low false-negative and false-positive rates. Recently, it had also been used for sex chromosome aneuploidies (SCAs). To assess the clinical utility of NIPT for SCAs in Northeast China, we collected NIPT data from BGI 500 sequencing platform in the Center for Reproductive Medicine, Center for Prenatal Diagnosis of the First Hospital of Jilin University, and calculate the positive predictive value (PPV) and false positive rate (FPR). Results: A cohort of 14936 samples were analyzed by NIPT, and revealed 70 cases with SCAs high-risk, among them, 40 women agreed to undergo amniocentesis, but as many as 30 ones refused further diagnose. Based on verified fetal karyotype, 30.0% (12/40) were confirmed to be a true positive. Unluckily, the PPV for monosomy X performed 0%. Besides, positive 47,XXX were 46.67% (7/15), 40.00% (2/5) were positive for 47, XYY, and 42.86% (3/7) were positive for 47, XXY.Conclusions: In conclusion, our present results confirmed that NIPT sequenced by BGI 500 demonstrated lowest PPVs for 45,X, but the more accurate prediction for other SCAs, it is still a potential method for SCAs screening. Henceforth, we should focus on how to improve the test utility and provide better services for pregnant women in need.

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