scholarly journals Noninvasive prenatal testing: the aspects of its introduction into clinical practice

2019 ◽  
pp. 5-14
Author(s):  
D. O. Korostin ◽  
D. A. Plakhina ◽  
V. A. Belova
Keyword(s):  
Clinical Practice ◽  
Rapid Development ◽  
False Negative ◽  
Prenatal Testing ◽  
Noninvasive Prenatal Testing ◽  
Negative Results ◽  
Free Dna ◽  
False Negative Results ◽  
Fetal Aneuploidies ◽  
Expert Community

The last couple of years have witnessed the rapid development of prenatal molecular-based screening for fetal aneuploidies that utilizes the analysis of cell-free DNA circulating in the bloodstream of a pregnant woman. The present review looks at the potential and limitations of such testing and the possible causes of false-positive and false-negative results. The review also describes the underlying principles of data acquisition and analysis the testing involves. In addition, we talk about the opinions held by the expert community and some aspects of legislation on the use of noninvasive prenatal testing (NIPT) in clinical practice in the countries where NIPT is much more widespread than in Russia.

scholarly journals Unexplained False Negative Results in Noninvasive Prenatal Testing: Two Cases Involving Trisomies 13 and 18

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
R. Hochstenbach ◽  
G. C. M. L. Page-Christiaens ◽  
A. C. C. van Oppen ◽  
K. D. Lichtenbelt ◽  
J. J. T. van Harssel ◽  
...  
Keyword(s):  
False Negative ◽  
Prenatal Testing ◽  
High Sensitivity ◽  
Trisomy 13 ◽  
Maternal Weight ◽  
Noninvasive Prenatal Testing ◽  
Root Cause ◽  
Negative Results ◽  
False Negative Results ◽  
Negative Case

Noninvasive prenatal testing (NIPT) validation studies show high sensitivity and specificity for detection of trisomies 13, 18, and 21. False negative cases have rarely been reported. We describe a false negative case of trisomy 13 and another of trisomy 18 in which NIPT was commercially marketed directly to the clinician. Both cases came to our attention because a fetal anatomy scan at 20 weeks of gestation revealed multiple anomalies. Karyotyping of cultured amniocytes showed nonmosaic trisomies 13 and 18, respectively. Cytogenetic investigation of cytotrophoblast cells from multiple placental biopsies showed a low proportion of nontrisomic cells in each case, but this was considered too small for explaining the false negative NIPT result. The discordant results also could not be explained by early gestational age, elevated maternal weight, a vanishing twin, or suboptimal storage or transport of samples. The root cause of the discrepancies could, therefore, not be identified. The couples involved experienced difficulties in accepting the unexpected and late-adverse outcome of their pregnancy. We recommend that all parties involved in caring for couples who choose NIPT should collaborate to clarify false negative results in order to unravel possible biological causes and to improve the process of patient care from initial counseling to communication of the result.

scholarly journals 667. Next Generation Sequencing of Microbial Cell Free DNA in the Diagnosis and Treatment of Infectious Disease in Children: When Does the Result Justify the Cost?

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S436-S436
Author(s):  
Rachel Downey Quick ◽  
Kelli A Martinez ◽  
Susan M Russo ◽  
Sarah E McGwier ◽  
Rachel A Quirt ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Antimicrobial Resistance ◽  
False Negative ◽  
Next Generation ◽  
Cell Free Dna ◽  
Negative Results ◽  
Free Dna ◽  
False Negative Results ◽  
The Cost ◽  
Generation Sequencing

Abstract Background Pathogen testing using next-generation sequencing of microbial cell-free DNA (NGS cfDNA) is a promising diagnostic tool to identify pathogens that might not be detected using conventional lab evaluation. Considering the cost of this test, it is important to determine when it is most useful to the plan of care (POC). Figure 1. Unit of admission among cases Figure 2. Patient characteristics in cases determined to be valuable and not valuable to the plan of care (POC) Methods In this retrospective study, we collected data from the medical charts of 50 consecutive NGS cfDNA tests in a free-standing children’s hospital. We evaluated patients for demographics, underlying conditions, diagnosis at time of testing, conventional laboratory testing and timing, medical treatment, and NGS cfDNA test results for clinical relevance or false negative results compared to conventional testing. The primary goal was to identify patients for whom the NGS cfDNA testing affected the POC. Charts were reviewed, and determinations regarding whether the result influenced the POC were confirmed by a provider. Results We were unable to differentiate patients with clinically valuable NGS cfDNA results (Fig 1 & 2). Among those with NGS cfDNA results valuable to the POC (n=22), both negative and positive testing guided POC (13 valuable negative vs. 9 diagnostic cases). In the total sample, 5 cases (10%) had a clinically relevant pathogen identified through conventional testing, but not through NGS cfDNA and 2 cases had antimicrobial resistance on culture, which is not detected by NGS cfDNA. Conclusion While we did not find a specific clinical profile for NGS cfDNA use, positive results were essential to the diagnosis in 18% of cases with otherwise negative laboratory evaluation for the pathogen identified in NGS cfDNA. Negative tests affected the POC in 26% of cases by avoiding unnecessary antimicrobials in high risk immunocompromised patients and patients that presented with low-risk of infection, but unclear disease process. Caution must be exercised with reliance on this test with respect to antimicrobial resistance and risk of false negative results. Disclosures All Authors: No reported disclosures

scholarly journals Cell-free DNA screening for aneuploidies in 7113 pregnancies: single Italian centre study

2020 ◽  
Vol 102 ◽  
Author(s):  
Alvaro Mesoraca ◽  
Katia Margiotti ◽  
Claudio Dello Russo ◽  
Anthony Cesta ◽  
Antonella Cima ◽  
...  
Keyword(s):  
Sex Chromosome ◽  
Clinical Performance ◽  
False Negative ◽  
Prenatal Testing ◽  
High Sensitivity ◽  
Trisomy 13 ◽  
Sequencing Platform ◽  
Non Invasive ◽  
Negative Results ◽  
False Negative Results

Abstract Introduction Non-invasive prenatal testing (NIPT) using cell-free foetal DNA has been widely accepted in recent years for detecting common foetal chromosome aneuploidies, such as trisomies 13, 18 and 21, and sex chromosome aneuploidies. In this study, the practical clinical performance of our foetal DNA testing was evaluated for analysing all chromosome aberrations among 7113 pregnancies in Italy. Methods This study was a retrospective analysis of collected NIPT data from the Ion S5 next-generation sequencing platform obtained from Altamedica Medical Centre in Rome, Italy. Results In this study, NIPT showed 100% sensitivity and 99.9% specificity for trisomies 13, 18 and 21. Out of the 7113 samples analysed, 74 cases (1%) were positive by NIPT testing; foetal karyotyping and follow-up results validated 2 trisomy 13 cases, 5 trisomy 18 cases, 58 trisomy 21 cases and 10 sex chromosome aneuploidy cases. There were no false-negative results. Conclusion In our hands, NIPT had high sensitivity and specificity for common chromosomal aneuploidies such as trisomies 13, 18 and 21.

scholarly journals Robust clinical detection of SARS-CoV-2 variants by RT-PCR/MALDI-TOF multi-target approach

2021 ◽  
Author(s):  
Matthew M. Hernandez ◽  
Radhika Banu ◽  
Ana S. Gonzalez-Reiche ◽  
Adriana van de Guchte ◽  
Zenab Khan ◽  
...  
Keyword(s):  
New York ◽  
Rapid Development ◽  
False Negative ◽  
Sequencing Data ◽  
Rt Pcr ◽  
Maldi Tof ◽  
Negative Results ◽  
False Negative Results ◽  
Clinical Detection ◽  
Target Design

The COVID-19 pandemic sparked rapid development of SARS-CoV-2 diagnostics. However, emerging variants pose the risk for target dropout and false-negative results secondary to primer/probe binding site (PBS) mismatches. The Agena MassARRAY SARS-CoV-2 Panel combines RT-PCR and MALDI-TOF mass-spectrometry to probe for five targets across N and ORF1ab genes, which provides a robust platform to accommodate PBS mismatches in divergent viruses. Herein, we utilize a deidentified dataset of 1,262 SARS-CoV-2-positive specimens from Mount Sinai Health System (New York City) from December 2020 through April 2021 to evaluate target results and corresponding sequencing data. Overall, the level of PBS mismatches was greater in specimens with target dropout. Of specimens with N3 target dropout, 57% harbored an A28095T substitution that is highly-specific for the alpha (B.1.1.7) variant of concern. These data highlight the benefit of redundancy in target design and the potential for target performance to illuminate the dynamics of circulating SARS-CoV-2 variants.

scholarly journals Performance of Cell-Free DNA Sequencing-Based Non-invasive Prenatal Testing: Our Experience on 36456 both Singleton and Multiple Pregnancies.

2021 ◽  
Author(s):  
Marco La Verde ◽  
Luigia De Falco ◽  
Annalaura Torella ◽  
Giovanni Savarese ◽  
Pasquale Saverese ◽  
...  
Keyword(s):  
Dna Sequencing ◽  
Retrospective Analysis ◽  
False Negative ◽  
Screening Method ◽  
Prenatal Testing ◽  
Maternal Blood ◽  
Noninvasive Prenatal Testing ◽  
Cell Free Dna ◽  
Detection Rates ◽  
Free Dna

Abstract Background: To describe the clinical practice and performance of cell-free DNA sequencing-based noninvasive prenatal testing as a screening method for detecting trisomy 21, 18, and 13 (T21, T18, and T13, respectively), as well as sex chromosome aneuploidy (SCA), in a general Italian pregnancy population.Methods: The AMES-accredited laboratory offers noninvasive prenatal testing in maternal blood as a clinical screening test for foetal T21, T18, T13 and SCA. Samples were sequenced on a NextSeq 550 (Illumina) using the VeriSeq NIPT Solution v1 assay.Results: A retrospective analysis was performed on a cohort of 36456 consecutive maternal blood samples, including 35650 singleton pregnancies, 800 twin pregnancies, and 6 triplet pregnancies, which were tested between April 2017 and September 2019. The cohort included 46% elevated-risk and 54% low-risk patients. Genetic and/or clinical outcomes were available in 36000 cases (98.7%). In the overall cohort, 356 (1%) results were indicative of classic trisomy: 254 T21, 69 T18, and 33 T13. In addition, 145 results (0.4%) were indicative of SCA. Of the combined 501 screen-positive cases, 484 had confirmatory diagnostic testing results available: 99.2% (247/249) of T21 cases, 91.2% (62/68) of T18 cases, 84.4% (27/32) of T13 cases, and 86.7% (117/135) of SCA cases were confirmed. Follow-up data were available for 98.8% of the 35955 cases reported as unaffected by trisomy or SCA. No false negative cases were reported. The sensitivity of NIPT was 100.00% for T21 (95% Cl 98.47-100.0), T18 (95% Cl 94.17-100.0), T13 (95% Cl 87.54-100.0) and SCA (95% Cl 96.62-100.0). The specificities were 99.99% (95% Cl 99.98-100.0), 99.98% (95% Cl 99.96-100.0), 99.99% (95% Cl 99.97-100.0), and 99.95% (95% Cl 99.92-99.97) for T21, T18, T13, and SCA, respectively.Conclusion: This retrospective analysis of a large cohort of consecutive patients who had whole-genome sequencing-based NIPT for classic trisomies and SCA showed excellent detection rates and low false positive rates.

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