Opinion on a new and Challenging Tool in Prenatal Counseling: Non invasive Prenatal Testing by Fetal Cell-Free DNA in Maternal Blood

Abstract Background This paper describes the clinical practice and performance of cell-free DNA sequencing-based non-invasive prenatal testing (NIPT) as a screening method for fetal trisomy 21, 18, and 13 (T21, T18, and T13) and sex chromosome aneuploidies (SCA) in a general Italian pregnancy population. Methods The AMES-accredited laboratory offers NIPT in maternal blood as a screening test for fetal 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 36,456 consecutive maternal blood samples, including 35,650 singleton pregnancies, 800 twin pregnancies, and 6 triplet pregnancies. Samples were tested between April 2017 and September 2019. The cohort included 46% elevated-risk and 54% low-risk patients. A result indicative of a classic trisomy was found in 356 (1%) of singleton or twin samples: 254 T21, 69 T18, and 33 T13. In addition, 145 results (0.4%) were indicative of a SCA. Of the combined 501 screen-positive cases, 484 had confirmatory diagnostic testing. NIPT results were confirmed in 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. In the 35,955 cases reported as unaffected by a classic trisomy or SCA, no false negative cases were reported. Assuming that false negative results would be reported, the sensitivity of NIPT was 100.00% for T21 (95% Cl 98.47–100.0), T18 (95% Cl 94.17–100.0), and T13 (95% Cl 87.54–100.0). 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 shows excellent detection rates and low false positive rates.

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Performance of non‐invasive prenatal testing when fetal cell‐free DNA is absent

Ultrasound in Obstetrics and Gynecology ◽

10.1002/uog.14715 ◽

2014 ◽

Vol 45 (1) ◽

pp. 112-112 ◽

Cited By ~ 39

Author(s):

T. Takoudes ◽

B. Hamar

Keyword(s):

Prenatal Testing ◽

Fetal Cell ◽

Cell Free Dna ◽

Non Invasive ◽

Free Dna

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Non-Invasive Prenatal Testing Using Cell Free DNA in Maternal Plasma: Recent Developments and Future Prospects

Journal of Clinical Medicine ◽

10.3390/jcm3020537 ◽

2014 ◽

Vol 3 (2) ◽

pp. 537-565 ◽

Cited By ~ 35

Author(s):

Peter Benn

Keyword(s):

Prenatal Testing ◽

Maternal Plasma ◽

Future Prospects ◽

Cell Free Dna ◽

Non Invasive ◽

Free Dna ◽

Recent Developments

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A novel approach to stabilize fetal cell-free DNA fraction in maternal blood samples for extended period of time

PLoS ONE ◽

10.1371/journal.pone.0208508 ◽

2018 ◽

Vol 13 (12) ◽

pp. e0208508 ◽

Cited By ~ 1

Author(s):

M. Rohan Fernando ◽

Chao Jiang ◽

Gary D. Krzyzanowski ◽

Tifany Somer-Shely ◽

Wayne L. Ryan

Keyword(s):

Extended Period ◽

Maternal Blood ◽

Fetal Cell ◽

Cell Free Dna ◽

Blood Samples ◽

Free Dna ◽

Novel Approach

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Implementation of cell-free DNA-based non-invasive prenatal testing in a National Health Service Regional Genetics Laboratory

Genetics Research ◽

10.1017/s0016672319000119 ◽

2019 ◽

Vol 101 ◽

Cited By ~ 1

Author(s):

Fiona S. Togneri ◽

Mark D. Kilby ◽

Elizabeth Young ◽

Samantha Court ◽

Denise Williams ◽

...

Keyword(s):

National Health Service ◽

High Risk ◽

Health Service ◽

National Health ◽

Prenatal Testing ◽

Low Risk ◽

Trisomy 13 ◽

Cell Free Dna ◽

Non Invasive ◽

Free Dna

Abstract Background Non-invasive prenatal testing (NIPT) for the detection of foetal aneuploidy through analysis of cell-free DNA (cfDNA) in maternal blood is offered routinely by many healthcare providers across the developed world. This testing has recently been recommended for evaluative implementation in the UK National Health Service (NHS) foetal anomaly screening pathway as a contingent screen following an increased risk of trisomy 21, 18 or 13. In preparation for delivering a national service, we have implemented cfDNA-based NIPT in our Regional Genetics Laboratory. Here, we describe our validation and verification processes and initial experiences of the technology prior to rollout of a national screening service. Methods Data are presented from more than 1000 patients (215 retrospective and 840 prospective) from ‘high- and low-risk pregnancies’ with outcome data following birth or confirmatory invasive prenatal sampling. NIPT was by the Illumina Verifi® test. Results Our data confirm a high-fidelity service with a failure rate of ~0.24% and a high sensitivity and specificity for the detection of foetal trisomy 13, 18 and 21. Secondly, the data show that a significant proportion of patients continue their pregnancies without prenatal invasive testing or intervention after receiving a high-risk cfDNA-based result. A total of 46.5% of patients referred to date were referred for reasons other than high screen risk. Ten percent (76/840 clinical service referrals) of patients were referred with ultrasonographic finding of a foetal structural anomaly, and data analysis indicates high- and low-risk scan indications for NIPT. Conclusions NIPT can be successfully implemented into NHS regional genetics laboratories to provide high-quality services. NHS provision of NIPT in patients with high-risk screen results will allow for a reduction of invasive testing and partially improve equality of access to cfDNA-based NIPT in the pregnant population. Patients at low risk for a classic trisomy or with other clinical indications are likely to continue to access cfDNA-based NIPT as a private test.

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