Non-invasive prenatal diagnostics of aneuploidy using next-generation DNA sequencing technologies, and clinical considerations

2013 ◽  
Vol 51 (6) ◽  
Author(s):  
Yana N. Nepomnyashchaya ◽  
Artem V. Artemov ◽  
Sergey A. Roumiantsev ◽  
Alexander G. Roumyantsev ◽  
Alex Zhavoronkov
Keyword(s):  
Dna Sequencing ◽  
Chromosomal Abnormalities ◽  
Diagnostic Algorithm ◽  
Screening Tests ◽  
Next Generation ◽  
Non Invasive ◽  
Cell Free Fetal Dna ◽  
Wide Range ◽  
The Cost ◽  
Fetal Aneuploidies

AbstractRapidly developing next-generation sequencing (NGS) technologies produce a large amount of data across the whole human genome and allow a large number of DNA samples to be analyzed simultaneously. Screening cell-free fetal DNA (cffDNA) obtained from maternal blood using NGS technologies has provided new opportunities for non-invasive prenatal diagnosis (NIPD) of fetal aneuploidies. One of the major challenges to the analysis of fetal abnormalities is the development of accurate and reliable algorithms capable of analyzing large numbers of short sequence reads. Several such algorithms have recently been developed. Here, we provide a review of recent NGS-based NIPD methods as well as the available algorithms for short-read sequence analysis. We furthermore introduce the practical application of these algorithms for the detection of different types of fetal aneuploidies, and compare the performance, cost and complexity of each approach for clinical deployment. Our review identifies several main technologies and trends in NGS-based NIPD. The main considerations for clinical development for NIPD and screening tests using DNA sequencing are: accuracy, intellectual property, cost and the ability to screen for a wide range of chromosomal abnormalities and genetic defects. The cost of the diagnostic test depends on the sequencing method, diagnostic algorithm and volume of the tests. If the cost of sequencing equipment and reagents remains at or around current levels, targeted approaches for sequencing-based aneuploidy testing and SNP-based methods are preferred.

scholarly journals Non-Invasive Prenatal Testing: Current Perspectives and Future Challenges

Genes ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 15
Author(s):  
Luigi Carbone ◽  
Federica Cariati ◽  
Laura Sarno ◽  
Alessandro Conforti ◽  
Francesca Bagnulo ◽  
...  
Keyword(s):  
Prenatal Screening ◽  
Prenatal Testing ◽  
Non Invasive ◽  
Fetal Dna ◽  
Cell Free Fetal Dna ◽  
Common Causes ◽  
Future Challenges ◽  
Neurodevelopmental Impairment ◽  
Fetal Aneuploidies ◽  
Made In

Fetal aneuploidies are among the most common causes of miscarriages, perinatal mortality and neurodevelopmental impairment. During the last 70 years, many efforts have been made in order to improve prenatal diagnosis and prenatal screening of these conditions. Recently, the use of cell-free fetal DNA (cff-DNA) testing has been increasingly used in different countries, representing an opportunity for non-invasive prenatal screening of pregnant women. The aim of this narrative review is to describe the state of the art and the main strengths and limitations of this test for prenatal screening of fetal aneuploidies.

scholarly journals Assessment of a change of protocol of prenatal screening by inclusion of non-invasive prenatal diagnosis

2020 ◽  
Vol 1 (2) ◽  
Author(s):  
Rocío Cabra-Rodríguez ◽  
Guadalupe Bueno Rodríguez ◽  
Cristina Santos Rosa ◽  
Miguel Ángel Castaño López ◽  
Sonia Delgado Muñoz ◽  
...  
Keyword(s):  
Prenatal Screening ◽  
Chromosomal Abnormalities ◽  
Screening Program ◽  
High Sensitivity ◽  
Maternal Blood ◽  
Screening Tests ◽  
Loss To Follow Up ◽  
Non Invasive ◽  
Second Trimester Screening ◽  
Trimester Screening

AbstractObjectivesNon-invasive prenatal screening (NIPS) is a test for the detection of major fetal chromosomal abnormalities in maternal blood during pregnancy. The purpose of this study was to assess the performance of NIPS implemented within the framework of the Screening Program for Congenital Abnormalities of the Andalusian Health System.MethodsA retrospective observational study was undertaken to determine the number of NIPS tests performed since its introduction. The number of invasive diagnostic tests done after the implementation of NIPS in the patients included in the program between March 2016 and August 2017 was also quantified.ResultsA total of 6,258 combined first- and second trimester screening tests were performed, covering 95% of the population. In total, 250 subjects were identified as high risk, of whom 200 underwent NIPS after loss to follow-up. NIPS showed a sensitivity of 100% (95% CI: 76.84–100%) and a specificity of 99.46% (95% CI: 97.04–99.99%).ConclusionsThis test has proven to have a very high sensitivity and specificity. The results obtained demonstrate that the incorporation of NIPS in clinical practice minimizes the rate of miscarriages and reduces the frequency of invasive procedures by 70%.

Non-Invasive Testing, Non-Invasive Counseling

2015 ◽  
Vol 43 (2) ◽  
pp. 228-240 ◽  
Author(s):  
Rachel Rebouché
Keyword(s):  
Chromosomal Abnormalities ◽  
Genetic Test ◽  
Prenatal Testing ◽  
Private Companies ◽  
Major Health ◽  
Prenatal Health ◽  
Non Invasive ◽  
Fetal Dna ◽  
Cell Free Fetal Dna ◽  
A Company

A regulatory moment for prenatal health care is here. An increasing amount of legislative attention has concentrated on the decisions pregnant women make after prenatal testing. The impetus for this legislation is a new non-invasive prenatal genetic test (NIPT). From the beginning of pregnancy, cell-free fetal DNA travels across the placental lining into the mother’s bloodstream, increasing in quantity as the pregnancy progresses. Laboratories can now analyze that DNA for chromosomal abnormalities and for fetal sex at 10 weeks of gestation. NIPT, which relies on a sample of the pregnant woman’s blood, is painless, occurs early in pregnancy, and is available for clinical and commercial use. In 2013, major health insurance plans began to cover NIPT for certain populations of women, such as women over 35 years old. And private companies have started marketing prenatal testing kits directly to consumers, who return a blood sample from the prospective mother to a company laboratory.

Non-invasive prenatal testing (NIPT): limitations on the way to become diagnosis

Diagnosis ◽  
2015 ◽  
Vol 2 (3) ◽  
pp. 141-158 ◽  
Author(s):  
Ioanna Kotsopoulou ◽  
Panagiota Tsoplou ◽  
Konstantinos Mavrommatis ◽  
Christos Kroupis
Keyword(s):  
Prenatal Testing ◽  
Maternal Plasma ◽  
Screening Tests ◽  
Positive Finding ◽  
Non Invasive ◽  
Cell Free Fetal Dna ◽  
The Future ◽  
The Moment ◽  
Next Generation Sequencing Ngs ◽  
Near Future

AbstractWith the discovery of existing circulating cell-free fetal DNA (ccffDNA) in maternal plasma and the advent of next-generation sequencing (NGS) technology, there is substantial hope that prenatal diagnosis will become a predominately non-invasive process in the future. At the moment, non-invasive prenatal testing (NIPT) is available for high-risk pregnancies with significant better sensitivity and specificity than the other existing non-invasive methods (biochemical and ultrasonographical). Mainly it is performed by NGS methods in a few commercial labs worldwide. However, it is expected that many other labs will offer analogous services in the future in this fast-growing field with a multiplicity of in-house methods (e.g., epigenetic, etc.). Due to various limitations of the available methods and technologies that are explained in detail in this manuscript, NIPT has not become diagnostic yet and women may still need to undergo risky invasive procedures to verify a positive finding or to secure (or even expand) a negative one. Efforts have already started to make the NIPT technologies more accurate (even at the level of a complete fetal genome) and cheaper and thus more affordable, in order to become diagnostic screening tests for all pregnancies in the near future.

Peripheral neuropathic pain

2020 ◽  
Vol 47 (3) ◽  
pp. 265-283
Author(s):  
Douglas Murphy ◽  
Denise Lester ◽  
F. Clay Smither ◽  
Ellie Balakhanlou
Keyword(s):  
Nervous System ◽  
Neuropathic Pain ◽  
Peripheral Nervous System ◽  
Nerve Blocks ◽  
Peripheral Neuropathic Pain ◽  
Non Invasive ◽  
Wide Range ◽  
The Cost ◽  
And Control

Neuropathic pain (NP) can have either central nervous system causes or ones from the peripheral nervous system. This article will focus on the epidemiology, classifications, pathology, non-invasive treatments and invasive treatments as a general review of NP involving the peripheral nervous system. NP has characteristic symptomatology such as burning and electrical sensations. It occurs in up to 10% of the general population. Its frequency can be attributed to its occurrence in neck and back pain, diabetes and patients receiving chemotherapy. There are a wide range of pharmacologic options to control this type of pain and when such measures fail, numerous interventional methods can be employed such as nerve blocks and implanted stimulators. NP has a cost to the patient and society in terms of emotional consequences, quality of life, lost wages and the cost of assistance from the medical system and thus deserves serious consideration for prevention, treatment and control.

VP36 Cost-Effectiveness Of Non-Invasive Prenatal Testing For Down Syndrome

2017 ◽  
Vol 33 (S1) ◽  
pp. 165-166
Author(s):  
Estibalitz Orruño ◽  
Juan Carlos Bayón ◽  
Isabel Portillo ◽  
José Asua
Keyword(s):  
Down Syndrome ◽  
Cost Effectiveness ◽  
Prenatal Screening ◽  
Prenatal Testing ◽  
Cost Effective ◽  
Sensitivity Analyses ◽  
Non Invasive ◽  
Cell Free Fetal Dna ◽  
Primary Test ◽  
The Cost

INTRODUCTION:The analysis of cell-free fetal DNA in maternal blood, also called Non-Invasive Prenatal Testing (NIPT), represents an emerging technology and a possible alternative/complement to current prenatal screening based on biochemical and sonographic markers for Down Syndrome (DS) detection.The aim of the study was to compare the application of NIPT with the prenatal diagnosis/screening procedures currently applied in the Basque Country.METHODS:An analytical decision model was developed to assess the costs and consequences, comparing current prenatal screening, NIPT as a contingency test in high-risk cases and NIPT as a first-line screening test. An economic analysis was conducted to determine which strategy was more cost-effective. Sensitivity analyses were performed (1).RESULTS:For a population of 97,074 pregnant women in gestational week 14 and a cut-off point of 1:270, NIPT as a contingent test was not cost-effective, detecting two cases less of DS and causing a lower number of miscarriages related to invasive-testing (4 versus 23) at a slightly lower cost (EUR8,111,351 versus EUR8,901,872).For risk cut-off points of 1:500 or 1:1000 for contingent NIPT, the number of DS cases detected increased, as did the cost. It could be cost-effective compared with current prenatal screening, (EUR61,763 or EUR256,123 per extra DS case detected, respectively).Using the NIPT as a primary test detected more DS cases (296 versus 271) and caused less miscarriages (5 versus 23), at a substantially higher cost (EUR41,395,645 versus EUR8,901,872). Cost-effectiveness analysis indicated that it was more expensive and more effective.Univariant sensitivity-analysis showed that when the price of the NIPT as primary test was EUR76, it was dominant compared with current prenatal screening. It was also cost-effective compared with the NIPT as a contingent test (EUR9,869 per extra DS case detected).CONCLUSIONS:The study shows that NIPT had higher detection rates for DS in different scenarios, but the cost constitutes a limiting factor for implementation in the Basque Health System.

scholarly journals Optimal Detection of Fetal Chromosomal Abnormalities by Massively Parallel DNA Sequencing of Cell-Free Fetal DNA from Maternal Blood

2011 ◽  
Vol 57 (7) ◽  
pp. 1042-1049 ◽  
Author(s):  
Amy J Sehnert ◽  
Brian Rhees ◽  
David Comstock ◽  
Eileen de Feo ◽  
Gabrielle Heilek ◽  
...  
Keyword(s):  
Dna Sequencing ◽  
Chromosomal Abnormalities ◽  
Maternal Blood ◽  
Massively Parallel ◽  
Sequencing Data ◽  
Training Set ◽  
Fetal Dna ◽  
Cell Free Fetal Dna ◽  
Independent Test ◽  
Massively Parallel Dna Sequencing

BACKGROUND Massively parallel DNA sequencing of cell-free fetal DNA from maternal blood can detect fetal chromosomal abnormalities. Although existing algorithms focus on the detection of fetal trisomy 21 (T21), these same algorithms have difficulty detecting trisomy 18 (T18). METHODS Blood samples were collected from 1014 patients at 13 US clinic locations before they underwent an invasive prenatal procedure. All samples were processed to plasma, and the DNA extracted from 119 samples underwent massively parallel DNA sequencing. Fifty-three sequenced samples came from women with an abnormal fetal karyotype. To minimize the intra- and interrun sequencing variation, we developed an optimized algorithm by using normalized chromosome values (NCVs) from the sequencing data on a training set of 71 samples with 26 abnormal karyotypes. The classification process was then evaluated on an independent test set of 48 samples with 27 abnormal karyotypes. RESULTS Mapped sites for chromosomes of interest in the sequencing data from the training set were normalized individually by calculating the ratio of the number of sites on the specified chromosome to the number of sites observed on an optimized normalizing chromosome (or chromosome set). Threshold values for trisomy or sex chromosome classification were then established for all chromosomes of interest, and a classification schema was defined. Sequencing of the independent test set led to 100% correct classification of T21 (13 of 13) and T18 (8 of 8) samples. Other chromosomal abnormalities were also identified. CONCLUSION Massively parallel sequencing is capable of detecting multiple fetal chromosomal abnormalities from maternal plasma when an optimized algorithm is used.

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