What Potent Blood: Non-Invasive Prenatal Genetic Diagnosis and the Transformation of Modern Prenatal Care

2007 ◽  
Vol 33 (1) ◽  
pp. 9-53 ◽  
Author(s):  
Carolyn Jacobs Chachkin
Keyword(s):  
Genetic Disorders ◽  
Genetic Disorder ◽  
Genetic Material ◽  
Genetic Diagnosis ◽  
Prenatal Testing ◽  
Maternal Blood ◽  
Non Invasive ◽  
Tay Sachs Disease ◽  
Promising Solution ◽  
Low Levels

What potent blood hath modest May,What fiery force the earth renews,The wealth of forms, the flush of hues ….—Ralph Waldo EmersonSomeday soon, virtually any pregnant woman will be able to learn — with 98-99% accuracy — whether her fetus has contracted a serious genetic disorder by undergoing nothing more than an inexpensive, non-invasive blood test. For years, scientists have sought a method of prenatal testing that could boast both high levels of accuracy and low levels of risk. The most promising solution lies in an exciting recent discovery: tiny quantities of fetal cells and DNA cross over into the mother's bloodstream during pregnancy. If the fetal genetic material can be successfully isolated from the maternal blood, it can be used to diagnose a number of genetic disorders, such as Down Syndrome, cystic fibrosis, Tay-Sachs disease, and sickle cell anemia. Indeed, researchers have spent the last decade developing ways to accomplish this.

scholarly journals Would I have Wanted to Know? A Qualitative Exploration of Women’s Attitudes, Beliefs and Concerns about Non-Invasive Prenatal Testing for de novo Genetic Conditions after having a Child with a de novo Genetic Disorder

OBM Genetics ◽  
2021 ◽  
Vol 05 (04) ◽  
pp. 1-1
Author(s):  
Sarah Long ◽  
◽  
Roanna Lobo ◽  
Peter O'Leary ◽  
Jan E. Dickinson ◽  
...  
Keyword(s):  
Personal Growth ◽  
De Novo ◽  
Genetic Disorder ◽  
Single Gene ◽  
Genetic Diagnosis ◽  
Prenatal Testing ◽  
Phenomenological Approach ◽  
Population Screening ◽  
Chromosomal Disorders ◽  
Non Invasive

Non-invasive prenatal testing (NIPT) for a panel of 25 single gene disorders became available in Western Australia in 2020 and potentially may be able to test for panels of hundreds of disorders as is the case with reproductive carrier screening. How this information would be used by parents in a population screening model is unknown. We used a phenomenological approach to explore retrospectively whether mothers of children with single gene or chromosomal disorders would have wanted to know about their child’s genetic diagnosis prior to delivery. Themes were identified such as having a child with a de novo disorder and effect on pregnancy outcomes in hypothetical situations, impact on family function, the diagnostic journey and personal growth. These themes related to both the concept of expanded NIPT (ENIPT) and the situation of having a child with a de novo genetic disorder that could now hypothetically be detected through ENIPT. Opinions were divided about whether participants would have wanted to know about their affected child’s condition, indicating any expanded NIPT testing panels would need to be offered in the context of an appropriate comprehensive counselling program. How this would be provided on a population screening level and the role of genetic counselling needs further exploration.

Non-invasive prenatal testing for fetal aneuploidy by massively parallel DNA sequencing of maternal plasma: the future has arrived today/Nicht-invasiver Pränatal-Test auf fetale Aneuploidie mittels massiv-paralleler DNA-Sequenzanalyse im mütterlichen Plasma: in der Zukunft angekommen

2012 ◽  
Vol 36 (5) ◽  
Author(s):  
Amy Swanson ◽  
Christin Coffeen ◽  
Amy J. Sehnert
Keyword(s):  
Massively Parallel Sequencing ◽  
Prenatal Testing ◽  
The United States ◽  
Maternal Blood ◽  
Maternal Plasma ◽  
Massively Parallel ◽  
Clinical Implementation ◽  
Maternal Cell ◽  
Non Invasive ◽  
Fetal Aneuploidy

AbstractAfter decades of research, non-invasive prenatal testing (NIPT) using maternal blood to determine fetal chromosome status has found its way from the research laboratory into clinical practice, triggering a long-awaited paradigm shift in prenatal care. A variety of methods using sequencing of maternal cell-free DNA (cfDNA) have now been studied, primarily demonstrating their ability to detect the most common fetal aneuploidy, trisomy 21 (T21). The focus of this article is on massively parallel sequencing (MPS) with optimized sequence tag mapping and chromosome quantification, which accurately detects T21 as well as multiple other aneuploidies across the genome. The power of this technique resides in its high precision and reduction of variation within and between sequencing runs. Using MPS, classification of aneuploidy status for a given sample can be reliably assigned from the genetic information alone without the need to factor in other maternal pre-test risk or other clinical variables. Performance of this method has been prospectively demonstrated in a rigorous, blinded, multi-center study in the United States. The findings suggest that MPS can be incorporated into existing prenatal screening algorithms to reduce unnecessary invasive procedures. This technology and key considerations for clinical implementation are discussed.

Isolation and whole genome sequencing of fetal cells from maternal blood towards the ultimate non-invasive prenatal testing

2017 ◽  
Vol 37 (13) ◽  
pp. 1311-1321 ◽  
Author(s):  
Fang Chen ◽  
Ping Liu ◽  
Ying Gu ◽  
Zhu Zhu ◽  
Amulya Nanisetti ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Prenatal Testing ◽  
Maternal Blood ◽  
Whole Genome ◽  
Fetal Cells ◽  
Non Invasive

scholarly journals A novel high-throughput molecular counting method with single base-pair resolution enables accurate single-gene NIPT

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
David S. Tsao ◽  
Sukrit Silas ◽  
Brian P. Landry ◽  
Nelda P. Itzep ◽  
Amy B. Nguyen ◽  
...  
Keyword(s):  
Muscular Atrophy ◽  
Single Gene ◽  
Prenatal Testing ◽  
Maternal Blood ◽  
Beta Thalassemia ◽  
Analytical Sensitivity ◽  
Dna Molecules ◽  
Sequencing Data ◽  
Non Invasive ◽  
Single Base Pair

Abstract Next-generation DNA sequencing is currently limited by an inability to accurately count the number of input DNA molecules. Molecular counting is particularly needed when accurate quantification is required for diagnostic purposes, such as in single gene non-invasive prenatal testing (sgNIPT) and liquid biopsy. We developed Quantitative Counting Template (QCT) molecular counting to reconstruct the number of input DNA molecules using sequencing data. We then used QCT molecular counting to develop sgNIPTs of sickle cell disease, cystic fibrosis, spinal muscular atrophy, alpha-thalassemia, and beta-thalassemia. The analytical sensitivity and specificity of sgNIPT was >98% and >99%, respectively. Validation of sgNIPTs was further performed with maternal blood samples collected during pregnancy, and sgNIPTs were 100% concordant with newborn follow-up.

scholarly journals Performance of cell-free DNA sequencing-based non-invasive prenatal testing: experience on 36,456 singleton and multiple pregnancies

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Marco La Verde ◽  
Luigia De Falco ◽  
Annalaura Torella ◽  
Giovanni Savarese ◽  
Pasquale Savarese ◽  
...  
Keyword(s):  
Dna Sequencing ◽  
Retrospective Analysis ◽  
False Negative ◽  
Screening Method ◽  
Prenatal Testing ◽  
Maternal Blood ◽  
Cell Free Dna ◽  
Detection Rates ◽  
Non Invasive ◽  
Free Dna

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.

scholarly journals Do non-invasive prenatal tests promote discrimination against people with Down syndrome? What should be done?

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Klaus Zerres ◽  
Sabine Rudnik-Schöneborn ◽  
Wolfgang Holzgreve
Keyword(s):  
Down Syndrome ◽  
Pregnant Women ◽  
Maternity Care ◽  
Trisomy 21 ◽  
Genetic Diagnosis ◽  
Prenatal Testing ◽  
Reproductive Autonomy ◽  
Personal View ◽  
Non Invasive ◽  
Ethical Debate

Abstract By implementation of non-invasive prenatal testing (NIPT) for the diagnosis of Down syndrome (DS) in maternity care, an ethical debate is newly inflamed how to deal with this information. Fears of the consequences of an increased use of NIPT are justified with the same arguments when amniocentesis and preimplantation genetic diagnosis (PGD) were introduced decades ago. It can be expected that the prevalence of people with DS would significantly increase in Western societies as a result of the increasing age of pregnant women and the improved medical care for people with DS. The net effect as to whether an increasing uptake of NIPT will result in more abortions of fetuses with trisomy 21 cannot be reliably estimated. This holds true since more and more couples will use results of NIPT for information only, but will not opt for termination of pregnancy. Although parents love their children with DS, in a society where reproductive autonomy is seen as an achievement, access to NIPT cannot be limited. On this background, comprehensive and qualified pretest counseling is vital, also to avoid possible stigmatization of people with DS and as the resulting consequence to avoid feared deterioration in their living conditions, for which, however, there is no evidence to date. The personal view of a mother of a child with DS illustrates the complexity in dealing with NIPT, which does not allow simple answers and must be understood as a challenge for society as a whole.

Reproduction, fetal medicine and genomics

2020 ◽  
pp. 175573802097470
Author(s):  
Tessa Homfray ◽  
Judith Hayward ◽  
Imran Rafi
Keyword(s):  
Primary Care ◽  
Recurrent Miscarriage ◽  
Genetic Disorder ◽  
Prenatal Testing ◽  
Antenatal Screening ◽  
Fetal Abnormality ◽  
Fetal Medicine ◽  
Non Invasive ◽  
Genomic Technologies ◽  
Increased Risk

Identification of a genetic disorder within a family raises the question of risk of the genetic disorder to other family members and future pregnancies. This question is particularly pertinent when considering reproductive risks and choices. Primary care is crucial in identifying and managing couples at increased risk of having an affected pregnancy, both pre-conceptually and in early pregnancy, before the first midwife appointment. Genomic technologies have an increasing role in antenatal screening programmes and antenatal testing; specifically non-invasive prenatal testing considered in this article. Infertility, recurrent miscarriage and fetal abnormality may all have an underlying genetic cause.

scholarly journals A novel high-throughput molecular counting method with single base-pair resolution enables accurate single-gene NIPT

2019 ◽  
Author(s):  
David S. Tsao ◽  
Sukrit Silas ◽  
Brian P. Landry ◽  
Nelda Itzep ◽  
Amy B. Nguyen ◽  
...  
Keyword(s):  
Muscular Atrophy ◽  
Single Gene ◽  
Prenatal Testing ◽  
Maternal Blood ◽  
Beta Thalassemia ◽  
Analytical Sensitivity ◽  
Dna Molecules ◽  
Sequencing Data ◽  
Non Invasive ◽  
Single Base Pair

ABSTRACTNext-generation DNA sequencing is currently limited by an inability to count the number of input DNA molecules. Molecular counting is particularly needed when accurate quantification is required for diagnostic purposes, such as in single-gene non-invasive prenatal testing (sgNIPT) and liquid biopsy. We developed Quantitative Counting Template (QCT) molecular counting for reconstructing the number of input DNA molecules using sequencing data. We then used QCT molecular counting to develop sgNIPT of sickle cell disease, cystic fibrosis, spinal muscular atrophy, alpha-thalassemia, and beta-thalassemia. Incorporating molecular count information into a statistical model of disease likelihood led to analytical sensitivity and specificity of >98% and >99%, respectively. Validation of sgNIPT was further performed with maternal blood samples collected during pregnancy, and sgNIPT was 100% concordant with newborn follow-up.

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