Cell-free DNA screening for trisomies 21, 18, and 13 in pregnancies at low and high risk for aneuploidy with genetic confirmation

Dar, P.; Jacobson, B.; MacPherson, Cora; Egbert, Melissa; Malone, Fergal D.; Wapner, Ronald J.; Roman, Ashley S.; Khalil, Asma; Faro, Revital; Madankumar, Rajeevi; Edwards, Lance; Haeri, Sina; Silver, Robert M.; Vohra, Nidhi; Hyett, Jon; Clunie, Garfield; Demko, Zachary; Martin, Kimberly; Flood, Karen; Carlsson, Ylva; Doulaveris, Georgios; Malone, Ciara; Hallingström, Maria; Klugman, Susan; Clifton, Rebecca G.; Kao, Charlly; Hákonarson, Hákon; Norton, Mary E.

doi:10.1016/j.ajog.2022.01.019

Cited by 48 publications

(31 citation statements)

References 28 publications

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“…Our study would also undercount digynic triploidy, where very low FF often precludes any type of NIPT result 21 . With improvements in testing protocols that allow more reliable interpretation at lower FF, better detection of digynic triploidy can be anticipated 30 …”

Section: Discussionmentioning

confidence: 99%

“…21 With improvements in testing protocols that allow more reliable interpretation at lower FF, better detection of digynic triploidy can be anticipated. 30 In summary, detection of triploidy and other conditions associated with an extra haplotype is a secondary benefit of prenatal screening using a SNP-based NIPT. In conjunction with ultrasound, this testing allows early identification of a small set of high-risk pregnancies, some of which are also associated with risk to maternal health.…”

Section: Discussionmentioning

confidence: 99%

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Non‐invasive prenatal screening for fetal triploidy using single nucleotide polymorphism‐based testing: Differential diagnosis and clinical management in cases showing an extra haplotype

Kantor

Jelsema

et al. 2022

Prenatal Diagnosis

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Objective An extra haplotype is infrequently encountered in single nucleotide polymorphism(SNP)‐based non‐invasive prenatal testing (NIPT) and is usually attributed to an undetected twin or triploidy. We reviewed a large series to establish relative frequencies of these outcomes and identify alternative causes. Methods In 515,804 women receiving NIPT from September 2017 through March 2019, all results with an extra haplotype were reviewed. Known viable and vanished twin pregnancies were excluded. For positive cases, pregnancy outcome information was sought. Results Of 1005 results with an extra haplotype (1 in 513), pregnancy outcome was available for 773 cases: 11% were confirmed or suspected triploidy; 65% to vanished twin; 10% with pregnancy loss. Rare explanations included complete mole, chimera, undisclosed donor egg pregnancy, maternal organ transplant and one instance of maternal neoplasm. Among triploid cases that were detected and independently confirmed, 23/27 (85%) were diandric. Conclusion SNP‐based NIPT, with detection of an extra haplotype, is 11% predictive of triploidy. For results with an extra haplotype, ultrasound is recommended to establish viability, evaluate for twins (viable or vanished), and detect findings consistent with triploidy. Review of patient history, serum screening, and ultrasound will reduce the number of CVS or amniocenteses necessary to confirm a diagnosis of triploidy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Non‐invasive prenatal screening for fetal triploidy using single nucleotide polymorphism‐based testing: Differential diagnosis and clinical management in cases showing an extra haplotype

Kantor

Jelsema

et al. 2022

Prenatal Diagnosis

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“…Figure S1: Forest Plots of all Data. References [ 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , …”

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A Critical Evaluation of Validation and Clinical Experience Studies in Non-Invasive Prenatal Testing for Trisomies 21, 18, and 13 and Monosomy X

Demko

Prigmore

Benn

2022

JCM

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Non-invasive prenatal testing (NIPT) for trisomies 21, 18, 13 and monosomy X is widely utilized with massively parallel shotgun sequencing (MPSS), digital analysis of selected regions (DANSR), and single nucleotide polymorphism (SNP) analyses being the most widely reported methods. We searched the literature to find all NIPT clinical validation and clinical experience studies between January 2011 and January 2022. Meta-analyses were performed using bivariate random-effects and univariate regression models for estimating summary performance measures across studies. Bivariate meta-regression was performed to explore the influence of testing method and study design. Subgroup and sensitivity analyses evaluated factors that may have led to heterogeneity. Based on 55 validation studies, the detection rate (DR) was significantly higher for retrospective studies, while the false positive rate (FPR) was significantly lower for prospective studies. Comparing the performance of NIPT methods for trisomies 21, 18, and 13 combined, the SNP method had a higher DR and lower FPR than other methods, significantly so for MPSS, though not for DANSR. The performance of the different methods in the 84 clinical experience studies was consistent with validation studies. Clinical positive predictive values of all NIPT methods improved over the last decade. We conclude that all NIPT methods are highly effective for fetal aneuploidy screening, with performance differences across methodologies.

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“…Descriptive statistics was used to extract frequencies and percent for categorical variables and medians and standard deviation for continuous variables. Aneuploidy rates (like trisomy 21 in the second trimester) and aneuploidy for other isolated cardiac or other structural anomalies and CMA in general fetal population without, 9 and with anomalies 10 were compared to aneuploidy rates in fetuses with isolated VSD, as was previously described.…”

Section: Methodsmentioning

confidence: 99%

Prenatally diagnosed isolated perimembranous ventricular septal defect: Genetic and clinical implications

et al. 2022

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Objective To evaluate the incidence of chromosomal aberrations and the clinical outcomes following the prenatal diagnosis of isolated perimembranous ventricular septal defect (pVSD). Methods This retrospective study was composed of a cohort of pregnant women whose fetuses were diagnosed with isolated pVSD. Complete examinations of the fetal heart were performed, as well as a postnatal validation echocardiography follow‐up at 1 year of age. The collected data included: spontaneous closure of the pVSD, need for intervention, chromosomal aberrations and postnatal outcome. Results Fifty‐five pregnant women were included in the study. 34/55 (61.8%) of the fetuses underwent prenatal genetic workup which revealed no abnormal results. No dysmorphic features or abnormal neurological findings were detected postnatally in those who declined a prenatal genetic workup during the follow‐up period of 2 years. In 25/55 of the cases (45.4%), the ventricular septal defects (VSD) closed spontaneously in utero, whereas in 17 cases of this group (30.9%) the VSD closed during the first year of life. None of the large 3 VSDs cases (>3 mm), closed spontaneously. Conclusion Prenatally isolated perimembranous VSD has a favorable clinical outcome when classified as small‐to‐moderate size, children in our cohort born with such findings had no macroscopic chromosomal abnormalities.

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Cell-free DNA screening for trisomies 21, 18, and 13 in pregnancies at low and high risk for aneuploidy with genetic confirmation

Cited by 48 publications

References 28 publications

Non‐invasive prenatal screening for fetal triploidy using single nucleotide polymorphism‐based testing: Differential diagnosis and clinical management in cases showing an extra haplotype

Non‐invasive prenatal screening for fetal triploidy using single nucleotide polymorphism‐based testing: Differential diagnosis and clinical management in cases showing an extra haplotype

A Critical Evaluation of Validation and Clinical Experience Studies in Non-Invasive Prenatal Testing for Trisomies 21, 18, and 13 and Monosomy X

Prenatally diagnosed isolated perimembranous ventricular septal defect: Genetic and clinical implications

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