Comparison of noninvasive prenatal screening for defined pathogenic microdeletion/microduplication syndromes and nonsyndromic copy number variations: a large multicenter study.20221130162520

Comparison of noninvasive prenatal screening for defined pathogenic microdeletion/microduplication syndromes and nonsyndromic copy number variations: a large multicenter study.

Yang L, Bu G, Ma Y, Zhao J, Rezak J, La X. J Comp Eff Res. 2022;11(17):1277-1291. doi:10.2217/cer-2022-0088. Open Access: Learn more

Tags: Clinical Experience / Clinical Utility, 2022, China, CNVs

  • Retrospective study of over 19,000 pregnancies with NIPT.
  • “The positive predictive value (PPV) of CNV-seq for all types of CNV detected by NIPT was 35.4%, with PPVs of 61.5 and 27.6% for pathogenic MMSs [microdeletion/microduplication syndromes] and nonsyndromic CNVs, respectively. PPVs for NIPT showed different values depending on gestational characteristics, with the highest PPV for NIPT in the group with increased nuchal thickness (66.7%) and for the abnormal ultrasound group (57.1%). CNVs ≤5 Mb with normal ultrasound findings were generally associated with a healthy fetus.”
Clinical experience of noninvasive prenatal testing for rare chromosome abnormalities in singleton pregnancies.20221130162431

Clinical experience of noninvasive prenatal testing for rare chromosome abnormalities in singleton pregnancies.

Hu T, Wang J, Zhu Q, et al. Front Genet. 2022;13:955694. Published 2022 Sep 26. doi:10.3389/fgene.2022.955694. Open Access: Learn more

Tags: Clinical Experience / Clinical Utility, 2022, China, RAAs, CNVs

  • “The screen-positivity rate of NIPT for RCAs [rare chromosomal abnormalities] was 0.5% (842/158,824). Of the 528 gravidas who underwent amniocentesis, 29.2% (154/528) were confirmed to have positive prenatal SNP (single nucleotide polymorphism) array results. PPVs for rare autosomal trisomies (RATs) and segmental imbalances were 6.1% (7/115) and 21.1% (87/413), respectively. Regions of homozygosity/uniparental disomy (ROH/UPD) were identified in 9.5% (50/528) of gravidas. The PPV for clinically significant findings was 8.0% (42/528), including 7 cases with mosaic RATs, 30 with pathogenic/likely pathogenic copy number variants, and 5 with imprinting disorders.”
Genome-Wide Cell-Free DNA Test for Fetal Chromosomal Abnormalities and Variants: Unrestricted Versus Restricted Reporting.20221130162330

Genome-Wide Cell-Free DNA Test for Fetal Chromosomal Abnormalities and Variants: Unrestricted Versus Restricted Reporting.

Kwan AHW, Zhu X, Mar Gil M, et al. Diagnostics (Basel). 2022;12(10):2439. Published 2022 Oct 9. doi:10.3390/diagnostics12102439. Open Access: Learn more

Tags: Clinical Experience / Clinical Utility, 2022, China, RAAs, CNVs

  • “The main finding of this study is that by restricting the reporting of cfDNA results to the three major fetal trisomies, SCAs, and seven microdeletion syndromes and avoiding the reporting of additional findings such as RATs, structural chromosome imbalances, all CNVs or multiple aneuploidies, the false-positive rate can be significantly lowered from 0.93% (95% CI 0.59–1.47) to 0.17% (95% CI 0.06–0.50), but without a reduction in the no-result rate.”
Clinical, Cytogenetic and Molecular Cytogenetic Outcomes of Cell-Free DNA Testing for Rare Chromosomal Anomalies.20221130161556

Clinical, Cytogenetic and Molecular Cytogenetic Outcomes of Cell-Free DNA Testing for Rare Chromosomal Anomalies.

Basaran S, Has R, Kalelioglu IH, et al. Genes (Basel). 2022;13(12):2389. Published 2022 Dec 16. doi:10.3390/genes13122389. Open Access: Learn more

Tags: Clinical Utility / Clinical Experience, 2022, Turkey, RAAs, CNVs

  • “Out of 593 screen-positive results, 504 (85%) were for common aneuploidies, 40 (6.7%) for rare autosomal trisomies (RATs), and 49 (8.3%) for structural chromosome anomalies (SAs). Of the screen-positives for RATs, 20 cases were evaluated only in fetal tissue, and confined placental mosaicism (CPM) could not be excluded. Among cases with definitive results (n = 20), the rates of true positives, placental mosaics, and false positives were 35%, 45%, and 10%, respectively. Among screen-positives for SAs, 32.7% were true positives. The confirmation rate was higher for duplications than deletions (58.3% vs. 29.4%). The rate of chromosomal abnormality was 10.9% in the group of 256 screen-negatives with pathological ultrasound findings.”
  • Fetal growth restriction and adverse pregnancy outcomes were seen in four CPM cases (T4, T7, T16, and T22).
  • “We suggest that if cfDNA testing uncovers CPM, this does not mean cfDNA testing is ‘false positive.’ The detection of CPM needs adequate laboratory work and specific genetic counseling, including backup risk for low-level true fetal mosaicism and a higher risk for poor pregnancy outcomes.”
The potential of expanded noninvasive prenatal screening for detection of microdeletion and microduplication syndromes.20211130175107

The potential of expanded noninvasive prenatal screening for detection of microdeletion and microduplication syndromes.

Shi P, Wang Y, Liang H, et al. Prenat Diagn. 2021;41(10):1332-1342. doi:10.1002/pd.6002.

Tags: Clinical Experience / Clinical Utility, 2021, China, CNVs

  • “Of 36,970 ultrasound negative women there were 291 NIPS-Plus screen positive results indicating 237 aneuploidies and 54 MMS [microdeletion/microduplication syndromes]. Following amniocentesis, 171 (72%) were confirmed as genuine, comprising 3 T13s, 10 T18s, 61 T21s, 70 SCAs and 27 MMS.”
  • No significant difference in PPVs for MMS stratified by CNV size (PPV was 50% for CNVs < 5 Mb versus 50% for CNVs > 5 Mb).
  • “Conclusions: NIPS-Plus has the potential for clinical utility not only for routine aneuploid screening but also for MMS that do not show overt signs during early pregnancy ultrasound screening. We suggest that ultrasound with NIPS-Plus in combination with appropriate counselling could be considered as a comprehensive first-tier prenatal screening approach for all pregnant women.”
Clinical value for the detection of fetal chromosomal deletions/duplications by noninvasive prenatal testing in clinical practice.20211130175031

Clinical value for the detection of fetal chromosomal deletions/duplications by noninvasive prenatal testing in clinical practice.

Gou L, Suo F, Wang Y, et al. Mol Genet Genomic Med. 2021;9(6):e1687. doi:10.1002/mgg3.1687. Open Access: Learn more

Tags: Clinical Experience / Clinical Utility, 2021, China, CNVs

  • Retrospective study of 20,439 pregnancies undergoing NIPT. 60 women had NIPT results positive for deletions/duplication, of which 39 had invasive diagnostic testing and 9 were found to be true positive deletions/duplications.
  • Overall PPV for deletions/duplications was 23.1%.
  • Structural anomalies were identified by ultrasound in 3 cases which did not have diagnostic testing.
The application of expanded noninvasive prenatal screening for genome-wide chromosomal abnormalities and genetic counseling.20211130174946

The application of expanded noninvasive prenatal screening for genome-wide chromosomal abnormalities and genetic counseling.

Chen Y, Lai Y, Xu F, et al. J Matern Fetal Neonatal Med. 2021;34(16):2710-2716. doi:10.1080/14767058.2021.1907333. Open Access: Learn more

Tags: Clinical Experience / Clinical Utility, 2021, China, RAAs, CNVs

  • Study of 34,620 women with singleton pregnancies who underwent GW-NIPT.
  • PPVs were 70.06% for common trisomies, 40.22% for SCAs, 5.45% for other autosomal aneuploidies (of which T7, T8, T16, and T22 were the most frequent), and 51.22% for CNVs >5 Mb (with CNVs mostly detected on chromosomes 2, 4, 5, and 7).
Expanded noninvasive prenatal testing for fetal aneuploidy and copy number variations and parental willingness for invasive diagnosis in a cohort of 18,516 cases.20211130174853

Expanded noninvasive prenatal testing for fetal aneuploidy and copy number variations and parental willingness for invasive diagnosis in a cohort of 18,516 cases.

Ge Y, Li J, Zhuang J, et al. BMC Med Genomics. 2021;14(1):106. Published 2021 Apr 14. doi:10.1186/s12920-021-00955-6. Open Access: Learn more

Tags: Clinical Experience / Clinical Utility, 2021, China, RAAs, CNVs

  • Retrospective analysis of 24,702 cases of expanded NIPT.
  • PPVS were 6.45% for RATs and 50% for CNVs.
Non-invasive prenatal diagnosis for translocation carriers-YES please or NO go?20211130174624

Non-invasive prenatal diagnosis for translocation carriers-YES please or NO go?

Srebniak MI, Jehee FS, Joosten M, et al. Acta Obstet Gynecol Scand. 2021;100(11):2036-2043. doi:10.1111/aogs.14256. Open Access: Learn more

Tags: Clinical Experience / Clinical Utility, 2021, Netherlands, CNVs

  • Retrospective study of 12 cases of fetal unbalanced familial translocations, with NIPT and CMA results available.
  • For 10/12 cases, the translocation was accurately detected by NIPT and the parental translocation was previously not known.
  • “Conclusions: This study supports the hypothesis that routine NIPS may be used for prenatal diagnosis of unbalanced inheritance of familial translocations, especially with prior knowledge of the translocation allowing focused examination of the involved chromosomal regions. Our study showed that routine shallow sequencing designed for aneuploidy detection in cell free DNA may be sufficient for higher resolution NIPS, if specialized copy number software is used and if sufficient fetal fraction is present.”
Cell-free fetal DNA testing and its correlation with prenatal indications.20211130174455

Cell-free fetal DNA testing and its correlation with prenatal indications.

Wang JW, Lyu YN, Qiao B, et al. BMC Pregnancy Childbirth. 2021;21(1):585. Published 2021 Aug 24. doi:10.1186/s12884-021-04044-5. Open Access: Learn more

Tags: Clinical Experience / Clinical Utility, 2021, China, RAAs, CNVs

  • Retrospective analysis of pregnant women with high-risk indications.
  • 189 (1.32%) positive NIPT results were identified and 113/189 (59.79%) were confirmed by invasive diagnostic testing. Abnormal serum screening was the most common indication, followed by advanced maternal age.
  • PPVs were 91.84% for T21, 68.75% for T18, 37.50% for T13, 66.67% for SCAs, 14.29% for other autosomal aneuploidy abnormalities, and 6.45% for CNVs.
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