Expanding the Scope of Non-invasive Prenatal Testing to Detect Fetal Chromosomal Copy Number Variations.
Chen S, Zhang L, Gao J, et al. Front Mol Biosci. 2021;8:649169. Published 2021 May 12. doi:10.3389/fmolb.2021.649169. Open Access: Learn more
Tags: Laboratory Performance / Laboratory Experience, 2021, China, CNVs
- Analyzed the NIPT screen positive rate at different read depths and identified a strategy for fetal CNV detection.
- “Increasing read depth in NGS [next-generation sequencing] improves the positive CNV detection rate while lowering the false positive detection rate. NIPT by NGS may be an accurate method of fetal chromosome analysis and reduce the rate of birth defects.”
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.
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.
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.
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.
Performance of a Paired-End Sequencing-Based Noninvasive Prenatal Screening Test in the Detection of Genome-Wide Fetal Chromosomal Anomalies.
Pertile MD, Flowers N, Vavrek D, et al. Clin Chem. 2021;67(9):1210-1219. doi:10.1093/clinchem/hvab067. Open Access: Learn more
Tags: Laboratory Experience / Laboratory Performance, 2021, Australia, RAAs, CNVs
- Study of GW-NIPT in 2335 frozen plasma samples to detect GW chromosomal anomalies including common trisomies, SCAs, RAAs, and partial deletions and duplications.
- “Genome-wide screening analysis including known mosaics correctly classified 27/28 RAAs and 20/27 partial deletions/duplications with a specificity of 99.80% for both anomalies, and an overall genome-wide specificity for all anomalies of 99.34%.”
- ”With an overall genome-wide clinical specificity for any anomaly of 99.34%, this genome-wide screen allows for detection of a broad range of chromosomal anomalies while retaining a clinical specificity far superior to the ~5% false-positive rate of serum screening.”
Diagnostic testing after positive results on cell free DNA screening: CVS or Amnio?
Mardy AH, Norton ME. Prenat Diagn. 2021;41(10):1249-1254. doi:10.1002/pd.6021.
Tags: Review / Meta-Analysis, 2021, International, RAAs
- Review of the literature to provide recommendations on chorionic villus sampling (CVS) versus amniocentesis after a positive NIPT result for autosomal aneuploidies, monosomy X, and multiple aneuploidies.
- “Conclusion: Clinicians should consider rates of CPM, imprinting, ultrasound findings and maternal factors when considering whether to recommend amnio or CVS after an abnormal cfDNA result.”
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.
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.
Comprehensive Evaluation of Non-invasive Prenatal Screening to Detect Fetal Copy Number Variations.
Wang J, Zhang B, Zhou L, Zhou Q, Chen Y, Yu B. Front Genet. 2021;12:665589. Published 2021 Jul 16. doi:10.3389/fgene.2021.665589. Open Access: Learn more
Tags: Clinical Experience / Clinical Utility, Review / Meta-Analysis, 2021, International, CNVs
- “Among the 24,613 pregnant women who received NIPS, 124 (0.50%) were suspected to have fetal CNVs. Of these, 66 women underwent prenatal diagnosis with CMA and 13 had true-positive results. The positive predictive value (PPV) of NIPS for fetal CNVs was 19.7%. Among 1,161 women who did not receive NIPS and underwent prenatal diagnosis by CMA, 47 were confirmed to have fetal pathogenic CNVs. Retesting with NIPS indicated that 24 of these 47 cases could also be detected by NIPS, representing a detection rate (DR) of 51.1%.”
- “10 publications, namely, six retrospective studies and four prospective studies, met our criteria and were selected for a detailed full-text review. The reported DRs were 61.10-97.70% and the PPVs were 36.11-80.56%. The sizes of CNVs were closely related to the accuracy of NIPS detection. The DR was 41.9% (13/31) in fetuses with CNVs ≤ 3 Mb, but was 55.0% (11/20) in fetuses with CNVs > 3 Mb.”