731: Canadian women's attitudes toward noninvasive prenatal testing of fetal DNA in maternal plasma

Objective: This study was designed to investigate the efficiency of noninvasive prenatal testing (NIPT) for screening fetal sex chromosome aneuploidies (SCAs) through sequencing of cell-free DNA in maternal plasma. Methods: This is a retrospective study on the positive NIPT results for SCAs collected from our hospital between January 2012 and December 2018. Samples with positive NIPT results for SCAs were then confirmed by prenatal or postnatal karyotyping analysis. Results: After cytogenetic analysis, abnormal karyotypes were confirmed in 104 cases and the overall positive predictive value (PPV) of NIPT for SCAs was 43.40% (102/235). The most frequently detected karyotypes included 47,XXY (n = 42), 47,XXX (n = 20), 47,XYY (n = 16), and 45,X (n = 2). Meanwhile, 10 cases were confirmed with mosaic karyotype 45,X/46,XX and 14 cases with numerical or structural chromosome abnormalities, including a double trisomy 48,XXX,+18. Cytogenetic results from the other 131 cases showed normal XX or XY, which were discordant with NIPT results. Upon analysis of parental karyotypes, 29 (12.34%) showed false positivity in NIPT results that were caused by maternal sex chromosome abnormalities. Conclusion: NIPT is an effective screening tool for SCA with a PPV of 43.40%. Maternal karyotype abnormalities occurred in 12.34% of the cases with abnormal NIPT. Diagnostic testing of the fetus and the mother are recommended.

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Noninvasive Prenatal Testing by Nanopore Sequencing of Maternal Plasma DNA: Feasibility Assessment

Clinical Chemistry ◽

10.1373/clinchem.2015.245076 ◽

2015 ◽

Vol 61 (10) ◽

pp. 1305-1306 ◽

Cited By ~ 21

Author(s):

Suk Hang Cheng ◽

Peiyong Jiang ◽

Kun Sun ◽

Yvonne K Y Cheng ◽

K C Allen Chan ◽

...

Keyword(s):

Prenatal Testing ◽

Maternal Plasma ◽

Nanopore Sequencing ◽

Plasma Dna ◽

Noninvasive Prenatal Testing ◽

Feasibility Assessment

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An online tool for fetal fraction prediction based on direct size distribution analysis of maternal cell-free DNA

BioTechniques ◽

10.2144/btn-2020-0143 ◽

2020 ◽

Author(s):

Luca Bedon ◽

Josef Vuch ◽

Simeone Dal Monego ◽

Germana Meroni ◽

Vanna Pecile ◽

...

Keyword(s):

Size Distribution ◽

Prenatal Testing ◽

Distribution Analysis ◽

Blood Draw ◽

Noninvasive Prenatal Testing ◽

Cell Free Dna ◽

Maternal Cell ◽

Fetal Dna ◽

Free Dna ◽

Fetal Fraction

The discovery of circulating fetal DNA in the plasma of pregnant women has greatly promoted advances in noninvasive prenatal testing. Screening performance is enhanced with higher fetal fraction and analysis of samples whose fetal DNA fraction is lower than 4% are unreliable. Although current approaches to fetal fraction measurement are accurate, most of them are expensive and time consuming. Here we present a simple and cost-effective solution that provides a quick and reasonably accurate fetal fraction by directly evaluating the size distribution of circulating DNA fragments in the extracted maternal cell-free DNA. The presented approach could be useful in the presequencing stage of noninvasive prenatal testing to evaluate whether the sample is suitable for the test or a repeat blood draw is recommended.

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Validation of fetal DNA fraction estimation and its application in noninvasive prenatal testing for aneuploidy detection in multiple pregnancies

Prenatal Diagnosis ◽

10.1002/pd.5597 ◽

2019 ◽

Vol 39 (13) ◽

pp. 1273-1282 ◽

Cited By ~ 4

Author(s):

Min Chen ◽

Fuman Jiang ◽

Yulai Guo ◽

Huanchen Yan ◽

Jiayan Wang ◽

...

Keyword(s):

Prenatal Testing ◽

Multiple Pregnancies ◽

Noninvasive Prenatal Testing ◽

Fetal Dna

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1.1 Non-Invasive Prenatal Testing Using Cell Free Fetal DNA in Maternal Plasma: An Aid to Prenatal Sonographic Diagnosis: Abstract 1.1 Table

Archives of Disease in Childhood - Fetal and Neonatal Edition ◽

10.1136/archdischild-2013-303966.001 ◽

2013 ◽

Vol 98 (Suppl 1) ◽

pp. A1.1-A1

Author(s):

LS Chitty ◽

A Barrett ◽

F Mackay ◽

S Fielding ◽

N Lench

Keyword(s):

Prenatal Testing ◽

Maternal Plasma ◽

Sonographic Diagnosis ◽

Non Invasive ◽

Fetal Dna ◽

Cell Free Fetal Dna

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Universal Haplotype-Based Noninvasive Prenatal Testing for Single Gene Diseases

Clinical Chemistry ◽

10.1373/clinchem.2016.268375 ◽

2017 ◽

Vol 63 (2) ◽

pp. 513-524 ◽

Cited By ~ 54

Author(s):

Winnie W I Hui ◽

Peiyong Jiang ◽

Yu K Tong ◽

Wing-Shan Lee ◽

Yvonne K Y Cheng ◽

...

Keyword(s):

Single Gene ◽

Family Members ◽

Prenatal Testing ◽

Maternal Plasma ◽

Nucleotide Polymorphisms ◽

Plasma Dna ◽

Sequencing Technology ◽

Noninvasive Prenatal Testing ◽

Haplotype Phasing ◽

Mutational Status

Abstract BACKGROUND Researchers have developed approaches for the noninvasive prenatal testing of single gene diseases. One approach that allows for the noninvasive assessment of both maternally and paternally inherited mutations involves the analysis of single nucleotide polymorphisms (SNPs) in maternal plasma DNA with reference to parental haplotype information. In the past, parental haplotypes were resolved by complex experimental methods or inferential approaches, such as through the analysis of DNA from other affected family members. Recently, microfluidics-based linked-read sequencing technology has become available and allows the direct haplotype phasing of the whole genome rapidly. We explored the feasibility of applying this direct haplotyping technology in noninvasive prenatal testing. METHODS We first resolved the haplotypes of parental genomes with the use of linked-read sequencing technology. Then, we identified SNPs within and flanking the genes of interest in maternal plasma DNA by targeted sequencing. Finally, we applied relative haplotype dosage analysis to deduce the mutation inheritance status of the fetus. RESULTS Haplotype phasing and relative haplotype dosage analysis of 12 out of 13 families were successfully achieved. The mutational status of these 12 fetuses was correctly classified. CONCLUSIONS High-throughput linked-read sequencing followed by maternal plasma-based relative haplotype dosage analysis represents a streamlined approach for noninvasive prenatal testing of inherited single gene diseases. The approach bypasses the need for mutation-specific assays and is not dependent on the availability of DNA from other affected family members. Thus, the approach is universally applicable to pregnancies at risk for the inheritance of a single gene disease.

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