Current controversies in prenatal diagnosis 2: for those women screened by NIPT using cell free DNA, maternal serum markers are obsolete

2016 ◽  
Vol 36 (13) ◽  
pp. 1167-1171
Author(s):  
Yuval Yaron ◽  
Jon Hyett ◽  
Sylvie Langlois
Keyword(s):  
Prenatal Diagnosis ◽  
Serum Markers ◽  
Maternal Serum ◽  
Cell Free Dna ◽  
Free Dna

scholarly journals OC21.05: Implications of inconclusive results in prenatal maternal serum cell-free DNA testing

2017 ◽  
Vol 50 ◽  
pp. 44-44
Author(s):  
M. Smet ◽  
N. Chan ◽  
A. McLennan ◽  
F. da Silva Costa
Keyword(s):  
Maternal Serum ◽  
Dna Testing ◽  
Cell Free Dna ◽  
Free Dna

scholarly journals Non-Invasive Prenatal Diagnosis (NIPD) of Sickle-Cell Disease By Massively Parallel Sequencing of Cell-Free Fetal DNA in Maternal Serum

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2085-2085
Author(s):  
Yvonne Daniel ◽  
Julia Van Campen ◽  
Lee Silcock ◽  
Michael Yau ◽  
Joo Wook Ahn ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Massively Parallel Sequencing ◽  
Plasma Samples ◽  
Cell Disease ◽  
Cell Free Dna ◽  
Non Invasive ◽  
Free Dna ◽  
Cell Free Fetal Dna

Sickle cell disease (SCD) is the most common genetic haematological disorder worldwide. Around 300.000 affected infants are born every year, including at least 1000 in the United States. Prenatal diagnosis is currently carried out using amniotic fluid or chorionic villus sampling. These invasive procedures are perceived to have a small risk of miscarriage. The availability of non-invasive prenatal diagnosis (NIPD) is predicted to increase uptake of prenatal diagnosis for SCD, as it has no perceived miscarriage risk. NIPD may also be more readily implemented than invasive prenatal diagnosis in the low-resource countries in which SCD is the most prevalent. However, accurate NIPD of autosomal recessive disorders such as sickle cell disease has proven challenging as this requires detection of fetal inheritance of a maternal allele from a mixed maternal-fetal pool of cell-free DNA. We report the development of a targeted massively parallel sequencing assay for the NIPD of fetal SCD using cell-free fetal DNA from maternal plasma. No paternal or previous offspring samples were required. 44 clinical samples were analysed, including 37 plasma samples from pregnant SCD carriers and 7 plasma samples from women with SCD due to Hb SC. We used a relative mutation dosage based approach for the 37 samples from maternal SCD carriers (Hb AS or Hb AC), integrating Unique Molecular Identifiers (UMIs) into the analysis to improve the accuracy of wildtype and mutant allele counts. We used a separate wildtype allele detection approach for the 7 samples from women with compound heterozygous SCD, in whom the detection of wildtype cell-free DNA indicates the presence of a carrier fetus. The success of the assay was evaluated by comparing results with the established fetal sickle status as determined through either invasive prenatal diagnosis or newborn screening. During development, two key factors improved the accuracy of the results: i) Selective analysis of only smaller cell-free DNA fragments enhanced the fetal fraction for all samples, with greater effects observed in samples from earlier gestations. This approach improved diagnostic accuracy: for 3 out of 44 samples, the genotype was inconclusive or incorrect before size selection, but correct after size selection. ii) Modifications to DNA fragment hybridisation capture optimised the diversity of Unique Molecular Identifier-tagged molecules analysed. This led to improvements in the results obtained for 5 samples, with 3 previously inconclusive samples correctly called and 2 previously discrepant results moved into the inconclusive range. In total, 37 results were concordant with the established fetal sickle status; this included 30/37 samples from carrier women and 7/7 samples from women with sickle cell disease due to Hb SC. The remaining 7 carrier samples gave an inconclusive result, which for 3 samples was attributed to a low fetal fraction. Samples from as early as 8 weeks gestation were successfully genotyped. There were no false positive or false negative results. This study is the largest to use NGS-based NIPD on clinical plasma samples from pregnancies at risk of SCD. Efforts to validate the assay on a larger sample cohort and to reduce the inconclusive rate are warranted. This study shows that NIPD for SCD is approaching clinical utility and has the potential to provide increased choice to women with pregnancies at risk of sickle cell disease. Disclosures Silcock: Nonacus Ltd.: Employment.

First-Trimester Contingent Screening for Trisomy 21 by Fetal Nuchal Translucency and Maternal Serum Biomarkers and Maternal Blood Cell-Free DNA Testing

2018 ◽  
Vol 5 (3) ◽  
pp. 139-143
Author(s):  
Sarang Younesi ◽  
Shahram Savad ◽  
Soudeh Ghafouri-Fard ◽  
Mohammad Mahdi Taheri-Amin ◽  
Pourandokht Saadati ◽  
...  
Keyword(s):  
Blood Cell ◽  
Trisomy 21 ◽  
First Trimester ◽  
Nuchal Translucency ◽  
Maternal Blood ◽  
Maternal Serum ◽  
Serum Biomarkers ◽  
Dna Testing ◽  
Cell Free Dna ◽  
Free Dna

Prenatal Screening and Diagnosis

2018 ◽  
Author(s):  
Barbara O’Brien ◽  
Emily Willner
Keyword(s):  
Diagnostic Testing ◽  
Chorionic Villus ◽  
Clinical History ◽  
Maternal Serum ◽  
Specific Gene ◽  
Chorionic Villus Sampling ◽  
Genetic Syndromes ◽  
Cell Free Dna ◽  
Free Dna ◽  
Ultrasound Evaluation

Prenatal genetic testing offers patients and providers the opportunity to screen for aneuploidy, genetic syndromes, and congenital malformations during pregnancy. Screening options include taking a clinical history, evaluation of maternal serum markers or noninvasive cell-free DNA, and ultrasound evaluation during the first and second trimesters. Invasive diagnostic testing such as amniocentesis or chorionic villus sampling allows for further investigation of positive screening results and a directed test to identify aneuploidy as well as specific gene mutations and gain, loss, or rearrangement of genetic information. Laboratory methods for testing fetal samples differ by types of genetic abnormalities that can be detected and turnaround time for results; these methods include karyotype, fluorescence in situ hybridization, and microarray.   This review contains 5 figures, 5 tables and 43 references Key words: amniocentesis, aneuploidy, cell-free DNA, chorionic villus sampling, karyotype, microarray, prenatal genetic screening, ultrasonography  

Prenatal Screening

2018 ◽  
Author(s):  
Amber Mathiesen ◽  
Kali Roy
Keyword(s):  
Test Performance ◽  
Predictive Value ◽  
Prenatal Screening ◽  
Maternal Serum ◽  
Dna Testing ◽  
Maternal Serum Screening ◽  
Cell Free Dna ◽  
Free Dna ◽  
Serum Screening

This chapter provides information about a genetic counselor’s role in prenatal screening, including discussing and offering options to a patient, interpreting and providing results, or managing referrals based on abnormal results. It discusses how a screen is evaluated using sensitivity, specificity, positive predictive value, negative predictive value, and personal utility. It provides a detailed description of both maternal serum screening and cell-free DNA testing. The maternal serum screening discussion includes information on multiples of median, calculating risk, timing, pattern association, limitations, and follow-up. The review of cell-free DNA testing includes fetal fraction, methodology, test performance, limitations and considerations for testing, and follow-up. This chapter also provides a list of additional resources to use for cell-free DNA testing.

Kinetics of fetal cellular and cell-free DNA in the maternal circulation during and after pregnancy: implications for noninvasive prenatal diagnosis

Transfusion ◽  
2001 ◽  
Vol 41 (12) ◽  
pp. 1524-1530 ◽  
Author(s):  
Hiromichi Ariga ◽  
Hitoshi Ohto ◽  
Michael P. Busch ◽  
Shinya Imamura ◽  
Robert Watson ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Maternal Circulation ◽  
Cell Free Dna ◽  
Free Dna ◽  
Noninvasive Prenatal Diagnosis ◽  
Kinetics Of

GENOME-WIDE PROFILING AND HAPLOTYPING OF CELL-FREE DNA ENABLING COMBINED NON-INVASIVE PRENATAL DIAGNOSIS OF INHERITED MONOGENIC DISEASES AND ANEUPLOIDY

2019 ◽  
Vol 39 ◽  
pp. e10-e11
Author(s):  
Huiwen Che ◽  
Darine Vileila ◽  
Eftychia Dimitriadou ◽  
Jia Ding ◽  
Thierry Voet ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Cell Free Dna ◽  
Non Invasive ◽  
Free Dna ◽  
Genome Wide ◽  
Monogenic Diseases

Prenatal Screening and Diagnosis

2018 ◽  
Author(s):  
Barbara O’Brien ◽  
Emily Willner
Keyword(s):  
Diagnostic Testing ◽  
Chorionic Villus ◽  
Clinical History ◽  
Maternal Serum ◽  
Specific Gene ◽  
Chorionic Villus Sampling ◽  
Genetic Syndromes ◽  
Cell Free Dna ◽  
Free Dna ◽  
Ultrasound Evaluation

Prenatal genetic testing offers patients and providers the opportunity to screen for aneuploidy, genetic syndromes, and congenital malformations during pregnancy. Screening options include taking a clinical history, evaluation of maternal serum markers or noninvasive cell-free DNA, and ultrasound evaluation during the first and second trimesters. Invasive diagnostic testing such as amniocentesis or chorionic villus sampling allows for further investigation of positive screening results and a directed test to identify aneuploidy as well as specific gene mutations and gain, loss, or rearrangement of genetic information. Laboratory methods for testing fetal samples differ by types of genetic abnormalities that can be detected and turnaround time for results; these methods include karyotype, fluorescence in situ hybridization, and microarray.   This review contains 5 figures, 5 tables and 43 references Key words: amniocentesis, aneuploidy, cell-free DNA, chorionic villus sampling, karyotype, microarray, prenatal genetic screening, ultrasonography  

Smoking in pregnancy is associated with increased total maternal serum cell-free DNA levels

2008 ◽  
Vol 28 (3) ◽  
pp. 186-190 ◽  
Author(s):  
Adam C. Urato ◽  
Inga Peter ◽  
Jacob Canick ◽  
Geralyn Lambert-Messerlian ◽  
Andrea Pulkkinen ◽  
...  
Keyword(s):  
Maternal Serum ◽  
Cell Free Dna ◽  
Smoking In Pregnancy ◽  
Free Dna ◽  
In Pregnancy
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