scholarly journals Evaluation of a novel screening method for fetal aneuploidy using cell-free DNA in maternal plasma

2019 ◽  
Vol 27 (1) ◽  
pp. 1-8
Author(s):  
Richard P Porreco ◽  
Matthew Sekedat ◽  
Allan Bombard ◽  
Thomas J Garite ◽  
Kimberly Maurel ◽  
...  
Keyword(s):  
Test Performance ◽  
Trisomy 21 ◽  
Sex Chromosome ◽  
Screening Method ◽  
Sequencing Technology ◽  
Cell Free Dna ◽  
Predictive Values ◽  
Fetal Aneuploidy ◽  
Free Dna ◽  
Equivalent Test

Objective To evaluate the test performance of a novel sequencing technology using molecular inversion probes applied to cell-free DNA screening for fetal aneuploidy. Methods Two cohorts were included in the evaluation; a risk-based cohort of women receiving diagnostic testing in the first and second trimesters was combined with stored samples from pregnancies with fetuses known to be aneuploid or euploid. All samples were blinded to testing personnel before being analyzed, and validation occurred after the study closed and results were merged. Results Using the new sequencing technology, 1414 samples were analyzed. The findings showed sensitivities and specificities for the common trisomies and the sex chromosome aneuploidies at >99% (Trisomy 21 sensitivity 99.2 CI 95.6–99.2; specificity 99.9 CI 99.6–99.9). Positive predictive values among the trisomies varied from 85.2% (Trisomy 18) to 99.0% (Trisomy 21), reflecting their prevalence rates in the study. Comparisons with a meta-analysis of recent cell-free DNA screening publications demonstrated equivalent test performance. Conclusion This new technology demonstrates equivalent test performance compared with alternative sequencing approaches, and demonstrates that each chromosome can be successfully interrogated using a single probe.

scholarly journals Cell-free DNA Testing in Routine Practice: Characterisation of a Cohort with Positive Results for Trisomies, Sex Chromosome Anomalies and Microdeletions

2020 ◽  
Author(s):  
Ismail Tekesin
Keyword(s):  
Sex Chromosome ◽  
Screening Method ◽  
First Trimester ◽  
Routine Practice ◽  
Cell Free Dna ◽  
Patient Counselling ◽  
Chromosome Anomalies ◽  
Free Dna ◽  
Autosomal Aneuploidy ◽  
Current Guidelines

Abstract Introduction Cell-free DNA (cfDNA) testing is increasingly used as a screening method not only for trisomy (T) 21 but also for T18 and T13, sex chromosome anomalies (SCA) and microdeletions. Based on cases with a positive cfDNA result in our specialised prenatal practice, this study aims to characterise the usage of cfDNA testing and to estimate the positive predictive value (PPV) in routine practice in Germany. Patients and Methods In this retrospective study we analysed the data of all pregnant women with a positive cfDNA result seen between 09/2013 and 12/2019. Women were either referred due to the positive result or the test was initiated in our practice. The primary parameter of interest was the concordance of cfDNA tests with confirmatory genetic testing. Results We encountered 81 cases with a positive cfDNA test (T21: 49.4%; T18: 9.9%; T13: 8.6%; SCA: 22.2%; 22q12del: 8.6%). The PPV was 95.0% for T21, but considerably lower for T18 (55.6%) and T13 (28.6%). For SCAs it was 23.1% and no case with DiGeorge syndrome was confirmed. 63% of the patients had not received a fetal anomaly scan before cfDNA testing. In first-trimester fetuses with a cfDNA test predicting an autosomal aneuploidy, fetal anomalies were detected in 90.3% of the cases. No false positive case had an abnormal US result. Conclusions Despite the excellent specificity of cfDNA tests, the PPV for aneuploidies other than T21 is low in routine practice. In discordance with the current guidelines, cfDNA test is often used without a previous detailed anomaly scan. Our data provide valuable information to assist patient counselling and shared decision making.

Close but not quite: Two cases of sex chromosome aneuploidies outside the scope of cell free DNA screening

2018 ◽  
Vol 38 (8) ◽  
pp. 617-619
Author(s):  
Katelynn G. Sagaser ◽  
Blair Stevens ◽  
Jessica Davis ◽  
Hope Northrup ◽  
Aarti Ramdaney
Keyword(s):  
Sex Chromosome ◽  
Cell Free Dna ◽  
Free Dna ◽  
Sex Chromosome Aneuploidies

First-Trimester Contingent Screening for Trisomy 21 by Fetal Nuchal Translucency and Maternal Serum Biomarkers and Maternal Blood Cell-Free DNA Testing

2018 ◽  
Vol 5 (3) ◽  
pp. 139-143
Author(s):  
Sarang Younesi ◽  
Shahram Savad ◽  
Soudeh Ghafouri-Fard ◽  
Mohammad Mahdi Taheri-Amin ◽  
Pourandokht Saadati ◽  
...  
Keyword(s):  
Blood Cell ◽  
Trisomy 21 ◽  
First Trimester ◽  
Nuchal Translucency ◽  
Maternal Blood ◽  
Maternal Serum ◽  
Serum Biomarkers ◽  
Dna Testing ◽  
Cell Free Dna ◽  
Free Dna

Cell-Free DNA Screening for Fetal Aneuploidy

2021 ◽  
pp. 115-120
Author(s):  
Ashley N. Battarbee ◽  
Neeta L. Vora
Keyword(s):  
Trisomy 21 ◽  
Dna Analysis ◽  
Chromosomal Abnormalities ◽  
Area Under The Curve ◽  
First Trimester ◽  
Outcome Data ◽  
Cell Free Dna ◽  
High Risk Women ◽  
Free Dna ◽  
Trimester Screening

In a prospective, multicenter blinded study at 35 international centers, the Noninvasive Examination of Trisomy (NEXT) study evaluated the performance of cell-free DNA screening for fetal trisomy compared to standard first trimester screening with nuchal translucency and serum analytes in a routine prenatal population. Among the 15,841 women who had standard screening and cell-free DNA analysis with neonatal outcome data, there were 68 chromosomal abnormalities (1 in 236). Of these, 38 were Trisomy 21 (1 in 417). Cell-free DNA analysis had a higher area under the curve (AUC) for trisomy 21, compared to standard screening (0.999 vs. 0.958, p = 0.001). Cell-free DNA analysis also had greater sensitivity, specificity, and positive predictive value compared to standard screening for trisomy 21, 18, and 13. While cell-free DNA analysis cannot detect all chromosome abnormalities, it performed better than standard screening for detection of trisomies 21, 18, and 13 in a routine population including low- and high-risk women.

scholarly journals Cell-Free DNA Analysis of Targeted Genomic Regions in Maternal Plasma for Non-Invasive Prenatal Testing of Trisomy 21, Trisomy 18, Trisomy 13, and Fetal Sex

2016 ◽  
Vol 62 (6) ◽  
pp. 848-855 ◽  
Author(s):  
George Koumbaris ◽  
Elena Kypri ◽  
Kyriakos Tsangaras ◽  
Achilleas Achilleos ◽  
Petros Mina ◽  
...  
Keyword(s):  
Trisomy 21 ◽  
Dna Analysis ◽  
Prenatal Testing ◽  
Cost Effective ◽  
Maternal Plasma ◽  
Trisomy 13 ◽  
Cell Free Dna ◽  
Free Dna ◽  
Genomic Regions ◽  
Fetal Fraction

Abstract BACKGROUND There is great need for the development of highly accurate cost effective technologies that could facilitate the widespread adoption of noninvasive prenatal testing (NIPT). METHODS We developed an assay based on the targeted analysis of cell-free DNA for the detection of fetal aneuploidies of chromosomes 21, 18, and 13. This method enabled the capture and analysis of selected genomic regions of interest. An advanced fetal fraction estimation and aneuploidy determination algorithm was also developed. This assay allowed for accurate counting and assessment of chromosomal regions of interest. The analytical performance of the assay was evaluated in a blind study of 631 samples derived from pregnancies of at least 10 weeks of gestation that had also undergone invasive testing. RESULTS Our blind study exhibited 100% diagnostic sensitivity and specificity and correctly classified 52/52 (95% CI, 93.2%–100%) cases of trisomy 21, 16/16 (95% CI, 79.4%–100%) cases of trisomy 18, 5/5 (95% CI, 47.8%–100%) cases of trisomy 13, and 538/538 (95% CI, 99.3%–100%) normal cases. The test also correctly identified fetal sex in all cases (95% CI, 99.4%–100%). One sample failed prespecified assay quality control criteria, and 19 samples were nonreportable because of low fetal fraction. CONCLUSIONS The extent to which free fetal DNA testing can be applied as a universal screening tool for trisomy 21, 18, and 13 depends mainly on assay accuracy and cost. Cell-free DNA analysis of targeted genomic regions in maternal plasma enables accurate and cost-effective noninvasive fetal aneuploidy detection, which is critical for widespread adoption of NIPT.

Prenatal Screening

2018 ◽  
Author(s):  
Amber Mathiesen ◽  
Kali Roy
Keyword(s):  
Test Performance ◽  
Predictive Value ◽  
Prenatal Screening ◽  
Maternal Serum ◽  
Dna Testing ◽  
Maternal Serum Screening ◽  
Cell Free Dna ◽  
Free Dna ◽  
Serum Screening

This chapter provides information about a genetic counselor’s role in prenatal screening, including discussing and offering options to a patient, interpreting and providing results, or managing referrals based on abnormal results. It discusses how a screen is evaluated using sensitivity, specificity, positive predictive value, negative predictive value, and personal utility. It provides a detailed description of both maternal serum screening and cell-free DNA testing. The maternal serum screening discussion includes information on multiples of median, calculating risk, timing, pattern association, limitations, and follow-up. The review of cell-free DNA testing includes fetal fraction, methodology, test performance, limitations and considerations for testing, and follow-up. This chapter also provides a list of additional resources to use for cell-free DNA testing.

scholarly journals Fetal Aneuploidy Detection by Cell-Free DNA Sequencing for Multiple Pregnancies and Quality Issues with Vanishing Twins

2014 ◽  
Vol 3 (3) ◽  
pp. 679-692 ◽  
Author(s):  
Sebastian Grömminger ◽  
Erbil Yagmur ◽  
Sanli Erkan ◽  
Sándor Nagy ◽  
Ulrike Schöck ◽  
...  
Keyword(s):  
Dna Sequencing ◽  
Multiple Pregnancies ◽  
Cell Free Dna ◽  
Fetal Aneuploidy ◽  
Free Dna ◽  
Quality Issues
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