Circulating Fetal Cell-Free DNA Fractions Differ in Autosomal Aneuploidies and Monosomy X

Rava, Richard P.; Srinivasan, Anupama; Sehnert, Amy J.; Bianchi, Diana W.

doi:10.1373/clinchem.2013.207951

Cited by 160 publications

(184 citation statements)

References 20 publications

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“…Although the total fetal fraction of twin pregnancies might be higher than that of singletons10, the individual contribution from each twin is generally lower than that of a singleton8, 9; however, there may be exceptions. In our study, the average combined fetal fraction of both twins (16.1%) was higher than determined previously for singletons over similar gestational‐age ranges (12.6%; P = 0.001)21, and higher still than the average fetal fraction for a single twin (7.8%; P < 0.0001), consistent with the previously mentioned studies. Rava et al .…”

Section: Discussionsupporting

confidence: 92%

Aneuploidy screening by non‐invasive prenatal testing in twin pregnancy

Fosler

Winters

Jones

et al. 2017

Ultrasound in Obstet & Gyne

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ObjectivesTo describe our experience with non‐invasive prenatal testing (NIPT) in twin pregnancy.MethodsTwo sets of maternal blood samples from twin pregnancies were analyzed at our laboratory using NIPT: 115 stored samples from pregnancies with known outcome (Clinical Study A) and 487 prospectively collected samples for which outcomes were requested from providers (Clinical Study B). NIPT was used to screen for the presence of fetal aneuploidy on chromosomes 13, 18, 21, X and Y in all cases, and results were compared with outcomes when known.ResultsIn Clinical Study A, all 115 samples were classified correctly by NIPT: three cases of trisomy 21 (one fetus affected), one of monochorionic trisomy 18 (both fetuses affected) and 111 euploid. In Clinical Study B, a NIPT result was reported for 479 (98.4%) of the 487 samples. Aneuploidy was detected or suspected in nine (1.9%) cases: seven cases of trisomy 21 detected, one case of trisomy 21 suspected and one case with trisomy 21 detected and trisomy 18 suspected. Information on aneuploidy outcome was available for 171 (35.7%) cases in Clinical Study B. Of the nine cases with aneuploidy detected or suspected, six were confirmed to be a true positive in at least one twin based on karyotype or birth outcome and two were suspected to be concordant based on ultrasound findings; the one known discordant result was for the aneuploidy suspected case. No false negatives were reported.Conclusion NIPT performed well in the detection of trisomy 21 in twin pregnancy, with a combined false‐positive frequency for trisomies 13, 18 and 21 of 0% for Clinical Study A and 0.2% for Clinical Study B. © 2016 Illumina. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

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Section: Discussionsupporting

confidence: 92%

Aneuploidy screening by non‐invasive prenatal testing in twin pregnancy

Fosler

Winters

Jones

et al. 2017

Ultrasound in Obstet & Gyne

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“…20 However, fetal fraction is lower when the fetus has trisomy 18, 13, or monosomy X, although it is still above the threshold fetal fraction of 4% that is needed to obtain a result. 21 Therefore, we feel it is a coincidence, rather than an intrinsic problem of the test, that all our "unclassified" results occurred in the second and third trimester. In three morbidly obese patients, the NIPT yielded no result, as there was an insufficient fetal fraction for analysis.…”

Section: Discussionmentioning

confidence: 86%

A single center’s experience with noninvasive prenatal testing

Beamon

Hardisty

Harris

et al. 2014

Genetics in Medicine

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“…24 Others showed that a fetal fraction of DNA in Down syndrome cases is often the same or higher when compared to pregnancies with euploid fetuses. 46,47 Since the introduction of NIPS into clinical practice, fetal fraction has not been uniformly reported by laboratories. The described relationship between low fetal fraction and increased risk of aneuploidy adds to the importance of reporting the reason for a no-call and of indicating in the report whether a low fetal fraction was identified.…”

Section: How Are No-calls Avoided Interpreted and Managed? Fetal Frmentioning

confidence: 99%

Noninvasive prenatal screening for fetal aneuploidy, 2016 update: a position statement of the American College of Medical Genetics and Genomics

Gregg

Skotko

Benkendorf

et al. 2016

Genetics in Medicine

581

560

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guidelines and statements have assisted patients seeking prenatal screening information and health-care providers responsible for providing accurate and up-to-date information to their patients. [1][2][3] Until recently, noninvasive prenatal screening for aneuploidy relied on measurements of maternal serum analytes and/or ultrasonography. These have a false-positive rate of approximately 5% and detection rates of 50-95%, depending on the specific screening strategy used. Advances in genomic technologies led to noninvasive prenatal screening that relies on the presence of cell-free DNA derived from the placenta but circulating in maternal blood, which is referred to here as noninvasive prenatal screening (NIPS). Massive parallel sequencing of maternal and placental (also called fetal when speaking of the fraction of this DNA in maternal blood) fragments of DNA occurs simultaneously. Sequencing with quantification can be random, targeted, and followed by quantification or exploitation of single-nucleotide polymorphisms. [4][5][6][7][8] Alternatively, sequencing can take place by measuring the release of hydrogen ions as nucleotides are added to a DNA template (i.e., semiconductor sequencing). 9 Microarray technology can also be used to quantify DNA. 10 Bioinformatics that enable these methodologies is complex and proprietary. Since the introduction of NIPS in 2011, health-care providers and patients have experienced marketing pressures, rapidly evolving professional practice guidelines, and confusion regarding the appropriate role of Noninvasive prenatal screening using cell-free DNA (NIPS) has been rapidly integrated into prenatal care since the initial American College of Medical Genetics and Genomics (ACMG) statement in 2013. New evidence strongly suggests that NIPS can replace conventional screening for Patau, Edwards, and Down syndromes across the maternal age spectrum, for a continuum of gestational age beginning at 9-10 weeks, and for patients who are not significantly obese. This statement sets forth a new framework for NIPS that is supported by information from validation and clinical utility studies. Pretest counseling for NIPS remains crucial; however, it needs to go beyond discussions of Patau, Edwards, and Down syndromes. The use of NIPS to include sex chromosome aneuploidy screening and screening for selected copy-number variants (CNVs) is becoming commonplace because there are no other screening options to identify these conditions. Providers should have a more thorough understanding of patient preferences and be able to educate about the current drawbacks of NIPS across the prenatal screening spectrum. Laboratories are encouraged to meet the needs of providers and their patients by delivering meaningful screening reports and to engage in education. With health-care-provider guidance, the patient should be able to make an educated decision about the current use of NIPS and the ramifications of a positive, negative, or no-call result. Genet Med advance online publication 28 July 2016Key Words: cell-f...

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Circulating Fetal Cell-Free DNA Fractions Differ in Autosomal Aneuploidies and Monosomy X

Cited by 160 publications

References 20 publications

Aneuploidy screening by non‐invasive prenatal testing in twin pregnancy

Aneuploidy screening by non‐invasive prenatal testing in twin pregnancy

A single center’s experience with noninvasive prenatal testing

Noninvasive prenatal screening for fetal aneuploidy, 2016 update: a position statement of the American College of Medical Genetics and Genomics

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