scholarly journals Cytogenomic results following high-chance non-invasive prenatal testing: a UK national audit

2020 ◽  
Vol 102 ◽  
Author(s):  
Fiona S. Togneri ◽  
Stephanie K. Allen ◽  
Kathy Mann ◽  
Elaine Holgado ◽  
Sian Morgan
Keyword(s):  
Trisomy 21 ◽  
Prenatal Testing ◽  
Healthcare Systems ◽  
Trisomy 13 ◽  
National Audit ◽  
Private Provision ◽  
Non Invasive ◽  
The Uk ◽  
High Chance ◽  
Singleton Pregnancies

Abstract Objective Non-invasive prenatal testing (NIPT) is increasingly being adopted as a screening test in the UK and is currently accessed through certain National Health Service healthcare systems or by private provision. This audit aims to describe reasons for and results of cytogenomic investigations carried out within UK genetic laboratories following an NIPT result indicating increased chance of cytogenomic abnormality (‘high-chance NIPT result’). Method A questionnaire was sent out to 24 genetics laboratories in the UK and completed by 18/24 (75%). Results Data were returned representing 1831 singleton pregnancies. A total of 1329 (73%) invasive samples were taken following NIPT results showing a high chance of trisomy 21; this was confirmed in 1305 (98%) of these by invasive sampling. Trisomy 21 was confirmed in >99% of patients who also had high-screen risk results or abnormal scan findings. Amongst invasive samples taken due to NIPT results indicating a high chance of trisomy 18, 84% yielded a compatible result, and this number dropped to 49% for trisomy 13 and 51% for sex chromosomes. Conclusion In the UK, the majority of patients having invasive sampling for high-chance NIPT results are doing so following an NIPT result indicating an increased chance of common trisomies (92%). In this population, NIPT performs particularly well for trisomy 21, but less well for other indications.

scholarly journals Women’s choices in non-invasive prenatal testing for aneuploidy screening: results from a single centre prior to introduction in England

2019 ◽  
Vol 105 (1) ◽  
pp. 47-52 ◽  
Author(s):  
Adalina Sacco ◽  
Hilary Hewitt ◽  
Pranav Pandya
Keyword(s):  
Trisomy 21 ◽  
Prenatal Testing ◽  
First Trimester ◽  
Routine Care ◽  
Singleton Pregnancy ◽  
Aneuploidy Screening ◽  
Non Invasive ◽  
Contingency Model ◽  
The Uk ◽  
High Chance

ObjectiveTo evaluate patient choices and uptake of non-invasive prenatal testing (NIPT) for aneuploidy screening offered in a contingency model as part of routine care.MethodWe retrospectively reviewed data for all women with a singleton pregnancy attending for routine first trimester screening over an 18-month period. Women with a ‘high-chance’ of trisomy 21, 18 or 13 (≥1:150) were offered the choice of no further testing, NIPT or invasive testing, in line with the screening pathway recommended by the UK National Screening Committee.ResultsOf 9342 women attending for a first trimester ultrasound scan, 7939 women were included in this study. Of these, 352 had a high-chance screening result for trisomy 21, and 291 (82.7%) opted for NIPT. The proportion of women opting for NIPT decreased as the chance of trisomy 21 increased: uptake was 93.2%, 90.0%, 77.1% and 47.2% for women with a chance of 1:100–150, 1:50–99, 1:10–49 and >1:10, respectively. 516 women (5.5%) accessed primary NIPT screening in the private sector, and 638 women (6.8%) declined any aneuploidy screening or testing.ConclusionImplementation of NIPT testing in a contingency model has a high uptake in a non-research National Health Service setting; the rate of uptake is related to the combined test risk result.

scholarly journals The Clinical Application of Non-invasive Prenatal Genetic Testing in the Screening of Fetal Chromosomal Diseases

2021 ◽  
Author(s):  
Yu Pang ◽  
chaohong wang ◽  
Junxiang Tang ◽  
Jiansheng Zhu
Keyword(s):  
High Risk ◽  
Clinical Application ◽  
Trisomy 21 ◽  
Sex Chromosome ◽  
Chromosomal Abnormalities ◽  
Reference Value ◽  
Prenatal Testing ◽  
Trisomy 13 ◽  
Non Invasive ◽  
Chromosome Aneuploidy

Abstract Objective：To explore the efficacy and clinical application value of non-invasive prenatal testing (non-invasive prenatal testing, NIPT) for screening fetal chromosomal abnormalities. Methods: NIPT was performed on 25,517 pregnant women. The high-risk samples were compared with amniotic fluid and cord blood chromosome karyotype analysis. Some samples were further verified by microarray (CMA), and pregnancy outcomes were followed up. Results: Of all the cases examined, 25502 cases were detected successfully, and a total of 294 high-risk samples (1.15%) were detected, of which further diagnosis was made in 208 cases, true positive samples were detected in 96 cases, and further tests were refused in 86 cases.71 cases (0.28%) of autosomal aneuploid high-risk samples were detected and 51 cases were diagnosed, including 44 cases of trisomy 21 (T21), 5 cases of trisomy 18 (T18), and 2 cases of trisomy 13 (T13). The PPV was 90.90%, 45.45% and 33.33%, respectively. Thirteen high-risk samples of trisomy 21, 18, and 13 were detected, and 1 case was confirmed as T21 mosaic PPV was 8.33% NPV was 100%. High-risk samples of sex chromosome aneuploidy (SCA) were detected in 72 cases (0.28%), 23 cases were diagnosed, and the PPV was 40.07%. The PPV was 12.00%, 50.00%, 72.73% and 75.00%, respectively, and the PPV was 12.00%, 50.00%, 72.73% and 75.00%, respectively. High-risk samples of copy number variation (CNV) were detected in 104 cases (0.41%), and 18 cases were diagnosed, with a PPV of 32.14%. Other high-risk samples of chromosome aneuploidy were detected in 34 cases (0.13%), and 3 cases were diagnosed as T2, T9, and T16, respectively. PPV is 8.70%.Conclusion: NIPT is suitable for trisomy 21, 18, and 13 screening, especially for T21. It also has a certain reference value for SCA and microdeletion and microduplication syndromes（MMS）, and it is not recommended for screening for other chromosomal aneuploidies.

scholarly journals The Value of Non-Invasive Prenatal Testing in the Diagnosis of Birth Defects: Insights from a Large Multicentre Study in Southern China

2021 ◽  
Author(s):  
Meiying Cai ◽  
Na Lin ◽  
Xuemei Chen ◽  
Ying Li ◽  
Min Lin ◽  
...  
Keyword(s):  
Multicentre Study ◽  
Pregnant Women ◽  
Chromosomal Abnormalities ◽  
Southern China ◽  
Prenatal Testing ◽  
Copy Number Variations ◽  
Trisomy 13 ◽  
Detection Rates ◽  
Non Invasive ◽  
Large Multicentre Study

Abstract Non-invasive prenatal testing (NIPT) is a fast, safe, and non-disruptive diagnostic method. At present, few studies have evaluated the screening efficiency of NIPT positive predictive value (PPV) in study subjects. Here, the results of NIPT in pregnant women were retrospectively analysed, and the detection rate, PPV and follow-up data were evaluated to determine its clinical value. A large multicentre study was conducted involving 52,855 pregnant women who received NIPT. Based on gestational age, amniotic fluid or umbilical cord blood were extracted for simultaneous karyotype and chromosome microarray analysis (CMA) in NIPT-positive patients. Among the 52,855 cases, 754 were NIPT-positive, with a positivity rate of 1.4%. Karyotype analysis and/or CMA confirmed 323 cases of chromosomal abnormalities, with a PPV of 45.1%. PPV of Trisomy 21 (T21), Trisomy 18 (T18), Trisomy 13 (T13), sex chromosomal aneuploidies (SCA) and copy number variations (CNV) were 78.9%, 35.3%, 22.2%, 36.9% and 32.9%, respectively. The PPV of T21, T18, and T13 increased with age whereas, the PPV of SCA and CNVs had little correlation with age. The PPV was significantly high in patients with advanced age along with an abnormal ultrasound.NIPT had a high PPV for T21, and a low PPV for T13 and T18, while screening for SCA and CNVs showed clinical significance. However, in case of NIPT screening for SCA and CNVs, simultaneous karyotype and CMA should be performed to increase the detection rates. Interventional prenatal diagnosis is still required in NIPT-positive cases to avoid false positives or unnecessary termination of pregnancy.

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

2019 ◽  
Vol 101 ◽  
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.

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.

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 The Right to Know and the Right Not to Know Revisited: Part One

2017 ◽  
Vol 9 (1-2) ◽  
pp. 3-18 ◽  
Author(s):  
Roger Brownsword ◽  
Jeff Wale
Keyword(s):  
Genetic Information ◽  
Human Genetics ◽  
Prenatal Testing ◽  
Test Cases ◽  
Right To Know ◽  
Non Invasive ◽  
The Right To Know ◽  
Right Not To Know ◽  
The Uk ◽  
The Right

Abstract Prompted by developments in human genetics, a recurrent bioethical question concerns a person’s ‘right to know’ and ‘right not to know’ about genetic information held that is intrinsically related to or linked to them. In this paper, we will revisit the claimed rights in relation to two particular test cases. One concerns the rights of the 500,000 participants in UK Biobank (UKB) whose biosamples, already having been genotyped, will now be exome sequenced, and the other concerns the rights of pregnant women (and their children) who undergo non-invasive prenatal testing (NIPT)—a simple blood test that can reveal genetic information about both a foetus and its mother. This two-part paper is in four principal sections. First, we sketch the relevant features of our two test cases. Secondly, we consider the significance of recent legal jurisprudence in the UK and Singapore. Thirdly, we consider how, the jurisprudence apart, the claimed rights might be grounded. Fourthly, we consider the limits on the rights. We conclude with some short remarks about the kind of genetically aware society that we might want to be and how far there is still an opportunity meaningfully to debate the claimed rights.

Current status of non-invasive prenatal testing (NIPT): genetic counseling, dominant methods and overall performance

2016 ◽  
Vol 40 (5) ◽  
Author(s):  
Thomas Harasim ◽  
Imma Rost ◽  
Hanns-Georg Klein
Keyword(s):  
Genetic Counseling ◽  
Paradigm Shift ◽  
Sex Chromosome ◽  
Prenatal Testing ◽  
Diagnostic Procedures ◽  
Trisomy 13 ◽  
Current Status ◽  
Non Invasive ◽  
Overall Performance ◽  
Aneuploidy Testing

Abstract:The introduction of non-invasive prenatal testing (NIPT) into prenatal care represents a paradigm shift. With the absence of any intervention risk in contrast to invasive diagnostic procedures, NIPT has been widely adopted for the detection of fetal trisomy 13, 18 and 21. Additionally, fetal sex chromosome aneuploidy testing and sex determination are available, but can be compromised by both, medical and legal factors. Available validation studies were predominantly based on patients with a high

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