Fetal Sex Chromosome Testing by Maternal Plasma DNA Sequencing

Bianchi, Diana W.; Parsa, Saba; Bhatt, Sucheta; Halks-Miller, Meredith; Kurtzman, Kathryn N.; Sehnert, Amy J.; Swanson, Amy

doi:10.1097/aog.0000000000000637

Cited by 148 publications

(183 citation statements)

References 25 publications

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“…10,17 False positive cfDNA results have been demonstrated due to confined placental mosaicism (CPM), maternal low-level mosaicism, twin demise and rarely, maternal cancer. [18][19][20][21] All patients with positive cfDNA were offered prenatal diagnostic testing, and almost two-thirds of women had either a CVS or amniocentesis. In singletons with positive cfDNA for autosomal trisomy and either abnormal or unknown karyotype, the rate of termination was 67%.…”

Section: Discussionmentioning

confidence: 99%

Patient choice and clinical outcomes following positive noninvasive prenatal screening for aneuploidy with cell-free DNA (cfDNA)

et al. 2016

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Objective Evaluate patient choices and outcomes following positive cfDNA.Method Retrospective cohort study of women with positive cfDNA through two academic centers between March 2012 and December 2014. Patients were screened based on ACOG indications. Medical records reviewed for counseling, ultrasound findings, diagnostic testing, karyotype and outcome.Results CfDNA was positive in 114 women; 105 singletons and 9 twin pairs. CfDNA was positive for autosomal trisomy (21, 18, 13) in 96 (84.2%) and sex chromosome aneuploidy in 18 (15.8%). Certified genetic counselors performed 95% of post-cfDNA counseling. Prenatal diagnostic testing was pursued by 71/114 (62%). Karyotype was available in 91/105 (86.7%) singletons and confirmed aneuploidy in 75/91 (82.4%); the PPV of cfDNA with any ultrasound finding was 93.6% versus 58.6% without a finding. An abnormal sonographic finding was seen in 4/16 (25%) singletons with false positive cfDNA. Fetal termination occurred in 53/79 (67%) singletons and 3/5 (60%) twins with prenatal abnormal or unknown karyotype for autosomal trisomy. Eleven fetuses (11/56, 19.6%) were terminated for suspected autosomal trisomy without karyotype confirmation.Conclusion Patient choices following positive cfDNA are varied. Ultrasound modifies the PPV of cfDNA. Termination rates for aneuploidy are not higher than historical controls. Recommendation for karyotype confirmation prior to termination is not universally followed.

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Section: Discussionmentioning

confidence: 99%

Patient choice and clinical outcomes following positive noninvasive prenatal screening for aneuploidy with cell-free DNA (cfDNA)

et al. 2016

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“…58 Maternal medical, endocrine, and fertility history can help to identify the cause of a false-positive result. This includes patients with an organ transplantation from either a 46,XY individual or unknown gender donor.…”

Section: Long Stretches Of Homozygositymentioning

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

583

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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“…Reports from reference laboratories have been broadly consistent with the estimates of detection rates (DRs) and false-positive rates (FPRs) established in these trials [2][3][4][5][6]. Additionally, both proof of principle [7][8][9] and data from reference laboratories [10,11] have indicated that screening is possible for select sets of microdeletion syndromes.…”

Section: Introductionmentioning

confidence: 52%

“…A major difficulty in clinical experience studies has been that confirmation studies have been substantially incomplete [2][3][4]11] and this study also has incomplete followup data. Low follow-up rates can be attributable to multiple factors including referral of confirmatory testing to different laboratories and incomplete documentation.…”

Section: Discussionmentioning

confidence: 91%

A National Referral Laboratory’s Experience with the Implementation of SNP-Based Non-invasive Prenatal Screening for Fetal Aneuploidy and Select Microdeletion Syndromes

Santamaría¹,

Bermejo²,

Cigarrán³

et al. 2018

Journal of Fetal Medicine

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To retrospectively evaluate the successful test rate and performance of non-invasive prenatal screening (NIPS) for aneuploidies and microdeletions with international transportation of samples. Blood samples from Iberian women with singleton pregnancies were sent to a US laboratory for NIPS for aneuploidy and microdeletion syndromes (22q11.2, 1p36, Cri-du-chat, Prader Willi and Angelman). The NIPS methodology involved the analysis of single nucleotide polymorphisms in cell-free DNA in maternal plasma. Women with high-risk results were offered karyotyping and/or microarray confirmatory studies. Based on 14,175 women with successful testing (98.76% of all referrals), the overall test positive rate was 2.37% (1.9% for aneuploidy and 0.47% for microdeletion syndromes). Based on cases with known outcome, the positive predictive values (PPVs) were: for trisomy 21, 98.6%; trisomy 18, 85.7%; trisomy 13, 71.4%; monosomy-X, 87.5%; other sex chromosome aneuploidies, 100%; 22q11.2 deletion, 15.4%; and other microdeletions combined, 20%. With a protocol change that involved selective use of resequencing at a higher depth of read, the PPV for 22q11.2 deletion increased to 33.3 and 75% for the other microdeletions. Effective NIPS for both aneuploidies and select microdeletion syndromes can be provided even when this involves international transportation of blood specimens.

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Fetal Sex Chromosome Testing by Maternal Plasma DNA Sequencing

Cited by 148 publications

References 25 publications

Patient choice and clinical outcomes following positive noninvasive prenatal screening for aneuploidy with cell-free DNA (cfDNA)

Patient choice and clinical outcomes following positive noninvasive prenatal screening for aneuploidy with cell-free DNA (cfDNA)

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

A National Referral Laboratory’s Experience with the Implementation of SNP-Based Non-invasive Prenatal Screening for Fetal Aneuploidy and Select Microdeletion Syndromes

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