Performance of a Paired-End Sequencing-Based Noninvasive Prenatal Screening Test in the Detection of Genome-Wide Fetal Chromosomal Anomalies

Pertile, Mark D.; Flowers, Nicola; Vavrek, Darcy; Andrews, Daniel; Kalista, Tasha; Craig, Andrew; Deciu, Cosmin; Duenwald, Sven; Meier, Kristen; Bhatt, Sucheta

doi:10.1093/clinchem/hvab067

Cited by 33 publications

(38 citation statements)

References 37 publications

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“…This NIPT study was primarily focused on the clinical outcome of positive results and the clinical significance of RAA and CNVs. Based on additional available follow-up information, clinical outcome data for the common trisomies and SCAs were consistent with the published test performance of the manufacturer [23]. The clinical follow-up for cases where NIPT indicated a RAA or CNV reported here added to the limited data available in the published literature.…”

Section: Discussionsupporting

confidence: 77%

Initial Clinical Experience with NIPT for Rare Autosomal Aneuploidies and Large Copy Number Variations

Harasim

Neuhann

Behnecke

et al. 2022

JCM

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Objective: Amniocentesis, chorionic villi sampling and first trimester combined testing are able to screen for common trisomies 13, 18, and 21 and other atypical chromosomal anomalies (ACA). The most frequent atypical aberrations reported are rare autosomal aneuploidies (RAA) and copy number variations (CNV), which are deletions or duplications of various sizes. We evaluated the clinical outcome of non-invasive prenatal testing (NIPT) results positive for RAA and large CNVs to determine the clinical significance of these abnormal results. Methods: Genome-wide NIPT was performed on 3664 eligible patient samples at a single genetics center. For patients with positive NIPT reports, the prescribing physician was asked retrospectively to provide clinical follow-up information using a standardized questionnaire. Results: RAAs and CNVs (>7 Mb) were detected in 0.5%, and 0.2% of tested cases, respectively. Follow up on pregnancies with an NIPT-positive result for RAA revealed signs of placental insufficiency or intra-uterine death in 50% of the cases and normal outcome at the time of birth in the other 50% of cases. We showed that CNV testing by NIPT allows for the detection of unbalanced translocations and relevant maternal health conditions. Conclusion: NIPT for aneuploidies of all autosomes and large CNVs of at least 7 Mb has a low “non-reportable”-rate (<0.2%) and allows the detection of additional conditions of clinical significance.

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Section: Discussionsupporting

confidence: 77%

Initial Clinical Experience with NIPT for Rare Autosomal Aneuploidies and Large Copy Number Variations

Harasim

Neuhann

Behnecke

et al. 2022

JCM

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“…During the last decade, cfNIPT has been introduced worldwide as an efficient screening tool for detection of trisomies 13, 18, and 21 and potentially sex chromosomes, however, the positive predictive value for the SCAs is lower (Gadsbøll et al, 2020;Luo et al, 2021;Pertile et al, 2021). Prenatal diagnosis of SCAs in a fetus is complicated by the absence of confirmatory ultrasound findings beyond the increased nuchal translucency (Christiansen et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

“…Cell-free non-invasive prenatal testing (cfNIPT) through analysis of cell-free fetal DNA (cffDNA) in maternal plasma is widely implemented as a screening for fetal trisomy 13, 18, and 21, and often also sex chromosomal aneuploidies (SCAs) (Gadsbøll et al, 2020). cfNIPT is highly sensitive and specific for trisomies 21 (sensitivity: >99%), 13 (sensitivity: >98%), and 18 (sensitivity: >99%) (Rose et al, 2020), but the concordance for SCAs is lower (from 90.5 to 100%) (Pertile et al, 2021). Maternal SCAs is a known cause of false positive cfNIPT results, which may lead to redundant referral for invasive testing (Wang et al, 2015;Zhang et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Screening for Fetal Aneuploidy and Sex Chromosomal Anomalies in a Pregnant Woman With Mosaicism for Turner Syndrome—Applications and Advantages of Cell-Based NIPT

Jeppesen

Hatt²,

Singh³

et al. 2021

Front. Genet.

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Background: Cell-free NIPT and cell-based NIPT are risk-free testing options using maternal blood samples to screen for fetal aneuploidies, but the methods differ. For cell-free NIPT, the fetal fraction of cell-free DNA in plasma is analyzed with a high background of maternal DNA. In contrast, for cell-based NIPT, a limited number of the rare, intact fetal cells are isolated for the genetic analysis. This case demonstrates the differences regarding testing for fetal sex-chromosomes anomalies (SCAs) between these two tests.Materials and Methods: A pregnant woman with mosaicism for Turner syndrome opted for NIPT in first trimester. For the cell-free NIPT analysis, DNA extraction, genome-wide massive parallel sequencing, and data analysis were carried out as described by the kit manufacturer (Illumina©, San Diego, CA, USA). For cell-based NIPT, the first sample gave no result, but the woman consented to repeat cell-based NIPT. After whole genome amplification and STR analysis, fetal DNA from three individual fetal cells was subjected to chromosomal microarray (aCGH, Agilent oligoarray, 180 kb).Results: Fetal fraction was 7%, and cell-free NIPT showed 2 copies of chromosomes 13, 18, and 21 and a decreased proportion of chromosome X, suggestive of fetal Turner syndrome. In contrast, the cell-based NIPT result showed no aneuploidy and two X-chromosomes in the fetus.Conclusion: cell-based NIPT may provide a non-invasive testing option to screen for SCAs in women with mosaicism for monosomy-X in blood, where cell-free NIPT cannot discriminate whether the X-loss is maternal or fetal.

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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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Performance of a Paired-End Sequencing-Based Noninvasive Prenatal Screening Test in the Detection of Genome-Wide Fetal Chromosomal Anomalies

Cited by 33 publications

References 37 publications

Initial Clinical Experience with NIPT for Rare Autosomal Aneuploidies and Large Copy Number Variations

Initial Clinical Experience with NIPT for Rare Autosomal Aneuploidies and Large Copy Number Variations

Screening for Fetal Aneuploidy and Sex Chromosomal Anomalies in a Pregnant Woman With Mosaicism for Turner Syndrome—Applications and Advantages of Cell-Based NIPT

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

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