Implications of non-invasive prenatal testing for identifying and managing high-risk pregnancies

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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106: Non-invasive prenatal testing for trisomy 21 in high-risk women: a cost-effectiveness analysis

American Journal of Obstetrics and Gynecology ◽

10.1016/j.ajog.2013.10.139 ◽

2014 ◽

Vol 210 (1) ◽

pp. S67 ◽

Cited By ~ 1

Author(s):

Amelia Sutton ◽

Jennifer Durst ◽

Joseph Biggio ◽

Lorie Harper

Keyword(s):

Cost Effectiveness ◽

High Risk ◽

Trisomy 21 ◽

Prenatal Testing ◽

Cost Effectiveness Analysis ◽

High Risk Women ◽

Non Invasive ◽

Effectiveness Analysis

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Clinical utility and cost of non-invasive prenatal testing with cfDNA analysis in high-risk women based on a US population

The Journal of Maternal-Fetal & Neonatal Medicine ◽

10.3109/14767058.2013.770464 ◽

2013 ◽

Vol 26 (12) ◽

pp. 1180-1185 ◽

Cited By ~ 73

Author(s):

Ken Song ◽

Thomas J. Musci ◽

Aaron B. Caughey

Keyword(s):

High Risk ◽

Clinical Utility ◽

Prenatal Testing ◽

High Risk Women ◽

Non Invasive

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Estimation of Detection Rates of Aneuploidy in High-Risk Pregnancy Using an Approach Based on Nuchal Translucency and Non-Invasive Prenatal Testing: A Cohort Study

Fetal Diagnosis and Therapy ◽

10.1159/000381182 ◽

2015 ◽

Vol 38 (4) ◽

pp. 254-261 ◽

Cited By ~ 10

Author(s):

Asma Khalil ◽

Negar Mahmoodian ◽

Abhijit Kulkarni ◽

Tessa Homfray ◽

Aris Papageorghiou ◽

...

Keyword(s):

Cohort Study ◽

High Risk ◽

Chorionic Villus ◽

Prenatal Testing ◽

Nuchal Translucency ◽

Detection Rates ◽

Non Invasive ◽

Risk Pregnancy ◽

Increased Risk ◽

Clinically Significant

Objectives: The aim was to investigate aneuploidy detection using an approach based on nuchal translucency (NT) and non-invasive prenatal testing (NIPT). Methods: This was a cohort study including 5,306 high-risk pregnancies with NT measurements and chorionic villus samples (CVS) tested for full karyotype. Results: The fetal karyotype was normal in 4,172 (78.6%) cases and abnormal in 1,134 (21.4%), including 1,009 with a likely clinically significant adverse outcome. Universal CVS with full karyotyping would lead to the diagnosis of all clinically significant abnormalities. A policy of relying solely on NIPT would have led to the diagnosis of 88.9% of clinically significant abnormalities. A strategy whereby NIPT is the main method, with CVS reserved for cases with NT ≥3.0 mm, would require CVS in 21.7% of cases, identify 94.8% of significant abnormalities and avoid miscarriage in 41 pregnancies compared to CVS for all. Conclusions: A policy of NIPT for increased-risk cases and CVS with full karyotype if the NT was ≥3.0 mm reduced the risk of miscarriage yet still identified 95% of clinically significant aneuploidy.

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

10.21203/rs.3.rs-297925/v1 ◽

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.

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Next Generation Sequencing Based Non-invasive Prenatal Testing (NIPT): First Report From Saudi Arabia

Frontiers in Genetics ◽

10.3389/fgene.2021.630787 ◽

2021 ◽

Vol 12 ◽

Cited By ~ 1

Author(s):

Yusra Alyafee ◽

Abeer Al Tuwaijri ◽

Qamre Alam ◽

Muhammad Umair ◽

Shahad Haddad ◽

...

Keyword(s):

Saudi Arabia ◽

Next Generation Sequencing ◽

High Risk ◽

Pregnant Women ◽

Prenatal Testing ◽

Successful Implementation ◽

Next Generation ◽

Non Invasive ◽

Edwards Syndrome ◽

Generation Sequencing

Background: Non-invasive prenatal testing (NIPT) for aneuploidy in pregnant women screening has been recently established in Saudi Arabia. We aim from this study to report our experience in the implementation of this new technology in clinical practice and to assess factors influencing cell-free fetal (cffDNA) fraction and successful NIPT reporting.Methods: In total, 200 pregnant women were subjected to the NIPT test using standard methods. Next-generation sequencing (NGS) was used to analyze cffDNA in maternal plasma.Results: Out of the 200 NIPT cases, the average age of pregnant women was 35 ± 6 years (range: 21–48 years). The average cffDNA fraction of reported cases was 13.72% (range: 3–31%). Out of these 200 cases, 187 (93.5%) were at low risk, while 13 (6.5%) cases revealed high risk for aneuploidy. Among these chromosomal abnormalities, 7 (3.5%) cases of Down’s syndrome, 5 (2.5%) Edwards’ Syndrome, and only 1 case of (0.5%) Patau’s syndrome was observed. Out of the 13 high-risk cases, 2 (15.3%) were found in women below the age of 30.Conclusion: This is the first study reporting the successful implementation of an in-house NIPT screening service in Saudi Arabia. Our data showed high accuracy and sensitivity to detect high-risk cases indicating the usefulness of such a technique as an alternative to invasive testing and (hopefully) will change the common screening practice for pregnant women in Saudi Arabia.

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Non-invasive prenatal testing offered as part of a combined first-trimester screening program identifies tetrasomy 18p in a high-risk pregnancy

Prenatal Diagnosis ◽

10.1002/pd.4943 ◽

2016 ◽

Vol 36 (12) ◽

pp. 1112-1114 ◽

Cited By ~ 3

Author(s):

Dorte Launholt Lildballe ◽

Ida Vogel ◽

Ida Charlotte Bay Lund ◽

Inger Stornes ◽

Mette Warming Jørgensen ◽

...

Keyword(s):

High Risk ◽

Screening Program ◽

Prenatal Testing ◽

First Trimester ◽

High Risk Pregnancy ◽

First Trimester Screening ◽

Non Invasive ◽

Risk Pregnancy ◽

Tetrasomy 18P ◽

Trimester Screening

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Non-invasive Prenatal Testing (NIPT)

10.2310/obg.19129 ◽

2019 ◽

Author(s):

Courtney Manning ◽

Mary-Alice Abbott

Keyword(s):

High Risk ◽

Screening Test ◽

Sex Chromosome ◽

Diagnostic Testing ◽

Prenatal Testing ◽

Trisomy 18 ◽

Trisomy 13 ◽

Non Invasive ◽

Risk Result ◽

Cell Free Fetal Dna

Non-invasive prenatal testing (NIPT) is a screening test that can determine if a pregnancy is at high risk for the common aneuploidies by analyzing cell-free fetal DNA in the maternal bloodstream. The screening includes trisomy 21, trisomy 18, and trisomy 13, with the option of screening for sex chromosome aneuploidy and fetal sex. Traditionally this testing is offered to women that are at high risk for these aneuploidies, most commonly women of advanced maternal age. Individuals that receive a high risk result on NIPT should be offered diagnostic testing to confirm the result. New forms of NIPT have recently emerged, however the use of this technology as a screening test for other genetic conditions is not currently recommended by national professional society guidelines. Patients should be counseled and consented for NIPT, as this is an optional screening test. This review contains 2 tables, and 39 references. Keywords: NIPT, non-invasive prenatal testing, aneuploidy, Down syndrome, trisomy 18, trisomy 13, Turner syndrome, microdeletions, diagnostic testing

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