Genome-wide non-invasive prenatal testing in single- and multiple-pregnancies at any risk: Identification of maternal polymorphisms to reduce the number of unnecessary invasive confirmation testing

Oneda, Beatrice; Sirleto, Pietro; Baldinger, Rosa; Taralczak, Malgorzata; Joset, Pascal; Zweier, Christiane; Niedrist, Dunja; Azzarello-Burri, Silvia; Britschgi, Christian; Breymann, Christian; Ochsenbein‐Kölble, Nicole; Burkhardt, Tilo; Wisser, Josef; Zimmermann, Roland; Steindl, Katharina; Rauch, Anita

doi:10.1016/j.ejogrb.2020.05.070

Cited by 8 publications

(31 citation statements)

References 45 publications

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“…In addition, the PPV was 15.0% for CNVs < 5 Mb, 25.0% for CNVs within 5–10 Mb, and 50.0% for CNVs >10 Mb according to our results. Data from Oneda (Oneda et al, 2020) proofed that most (97.3%) of small CNVs detected by NIPT‐plus were mostly benign maternal variants, which may explain the low PPV for CNVs <5 Mb in our population. It seemed that there was a positive correlation between the PPV and the increase of CNVs size.…”

Section: Discussionmentioning

confidence: 68%

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Clinical application of expanded noninvasive prenatal testing for fetal chromosome abnormalities in a cohort of 39,580 pregnancies

Chen

Zhang

et al. 2022

American J of Med Genetics Pt A

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The aim of this study was to determine the predictive value of expanded noninvasive prenatal testing (NIPT‐plus) for fetal chromosome abnormalities in the second trimester (12–26 weeks). We conducted a retrospective cohort study of 39,580 pregnancies with NIPT‐plus. Screening positive cases were diagnosed with karyotyping and single‐nucleotide polymorphism array analysis (SNP array)/copy number variation sequencing (CNV‐seq) with follow‐up. The positive predictive values (PPVs) of trisomy 21, 18, and 13 (T21, T18, and T13), sex chromosome aneuploidies (SCAs), and microdeletion and microduplication syndromes (MMS) by NIPT‐plus were recorded. We assessed the predictive value of NIPT‐plus based on maternal age and conventional indications. Of 39,580 pregnancies with NIPT‐plus, 511 (1.3%) had prenatal screening positive results of fetal chromosome abnormality, of which 87.7% (448/511) had invasive prenatal diagnosis. NIPT‐plus performed better in predicting fetal SCAs and chromosome aneuploidies for pregnancies with advanced maternal age (AMA) than young maternal age (YMA). Besides, the PPVs of T21, T13, and chromosome aneuploidies showed an upward trend when comparison was based on maternal age in 5‐year subintervals. The termination rates of 45,X, 47,XXX, 47,XXY, and 47,XYY were 100% (11/11), 20.0% (3/15), 91.7% (22/24), and 7.1% (1/14) with postnatal follow‐up. Last but not least, the PPV for MMS is 41.7% (30/72), which may have a positive correlation between the size of CNVs. Pregnant women with screen‐positive results for common trisomies (T13, T18, and T21) were more willing to conduct invasive prenatal diagnosis compared to those with positive results for SCAs or MMS. However, the current study demonstrated SCAs and MMS had the lowest PPV. This highlights the importance of confirmatory prenatal diagnosis in those patients and the potential impact on genetic counseling and informative decision‐making.

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Section: Discussionmentioning

confidence: 68%

“…In addition, the PPV was 15.0% for CNVs < 5 Mb, 25.0% for CNVs within 5-10 Mb, and 50.0% for CNVs >10 Mb according to our results. Data from Oneda (Oneda et al, 2020)…”

Section: Discussionmentioning

confidence: 99%

Clinical application of expanded noninvasive prenatal testing for fetal chromosome abnormalities in a cohort of 39,580 pregnancies

Chen

Zhang

et al. 2022

American J of Med Genetics Pt A

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“…Most studies reported NIPS performance separately for each trisomy; however, there were some that reported overall performance for multiple outcomes. Oneda et al 29 evaluated NIPS performance for T21/T18/T13 in both prospective and retrospective populations. In their prospective cohort, sensitivity was reported as 100% (95% CI = 91.96%-100%), specificity was 99.97% (95% CI = 99.81%-100%), PPV was 97.78% (95% CI = 86.11%-99.68%), and NPV was 100% (no CI).…”

Section: Combined T21 T18 T13mentioning

confidence: 99%

Systematic evidence-based review: The application of noninvasive prenatal screening using cell-free DNA in general-risk pregnancies

Rose

Barrie

Malinowski

et al. 2022

Genetics in Medicine

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“…Previous studies from other research groups have focused on how cfDNA data metrics may be used to identify pregnancies at high risk of fetoplacental mosaicism, 3 or pregnancies at risk for maternal copy number variants. 4 The purpose of this study is to describe how a novel metric, "mosaicism ratio," is calculated in the event of a positive cfDNA result at one clinical laboratory, and how this metric can be used to identify cfDNA results more likely to be discordant with the genetic status of the fetus.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Impact of mosaicism ratio on positive predictive value of cfDNA screening

et al. 2020

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Objective: To examine the relationship between the fraction of cell-free DNA (cfDNA) affected by aneuploidy compared to the overall fetal fraction of a prenatal screening specimen and its effect on positive predictive value (PPV). Method: CfDNA specimens positive for trisomy 13, 18, and 21 with diagnostic outcomes were analysed over a 22-month period in one clinical laboratory. For each positive specimen, a "mosaicism ratio" (MR) was calculated by dividing the fraction of cfDNA affected by aneuploidy by the overall fetal fraction of the specimen. PPVs were calculated and analyzed based on various MR ranges. Results: Trisomy 13 was the aneuploidy most commonly seen in mosaic form, followed by trisomy 18 and trisomy 21. Significant differences in positive predictive values were noted for all three trisomies between samples with an MR in the "mosaic" versus "non-mosaic" range, as well as between results classified as "lowmosaic" versus "high-mosaic." Conclusion: PPVs may be influenced, in part, by the mosaicism ratio associated with a particular result. The data generated from this study may be useful in providing more personalized risk assessments for patients with positive cfDNA screening results.

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Genome-wide non-invasive prenatal testing in single- and multiple-pregnancies at any risk: Identification of maternal polymorphisms to reduce the number of unnecessary invasive confirmation testing

Cited by 8 publications

References 45 publications

Clinical application of expanded noninvasive prenatal testing for fetal chromosome abnormalities in a cohort of 39,580 pregnancies

Clinical application of expanded noninvasive prenatal testing for fetal chromosome abnormalities in a cohort of 39,580 pregnancies

Systematic evidence-based review: The application of noninvasive prenatal screening using cell-free DNA in general-risk pregnancies

Impact of mosaicism ratio on positive predictive value of cfDNA screening

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