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.
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.”
Case Report: Prenatal diagnosis of fetal tetrasomy 9p initially identified by non-invasive prenatal testing.
Yu J, Chen N, Chen M, Shen M, Qian Y, Dong M. Front Genet. 2022;13:1020525. Published 2022 Oct 31. doi:10.3389/fgene.2022.1020525. Open Access: Learn more
Tags: Case Report / Case Series, 2022, China, RAAs
- “Herein, we report a fetus of tetrasomy 9p without obvious phenotypic manifestations during the first trimester that was identified by non-invasive prenatal testing (NIPT). NIPT revealed that the gain of 9p24.3–9p11 that was approximately 46.36 Mb in size. Karyotyping of amniocytes indicated an additional marker in all metaphase. Chromosome microarray and fluorescence in situ hybridization on uncultured amniocytes revealed tetrasomic of 9p24.3q13, and that the supernumerary chromosome is a dicentric isochromosome consisted of two copies of the 9p arm. Taken together, it was indicated that the fetal karyotype was 47,XY,+idic (9) (q13), and that multiple techniques are crucial to the prenatal diagnosis.”
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.
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.
Outcomes of pregnancies with trisomy 16 mosaicism detected by NIPT: a series of case reports.
Peng H, Yang J, Wang D, Guo F, Hou Y, Yin A. Mol Cytogenet. 2021;14(1):44. Published 2021 Sep 20. doi:10.1186/s13039-021-00559-w. Open Access: Learn more
Tags: Case Report / Case Series, 2021, China, RAAs
- “NIPT detected 12 cases of T16 and 2 cases of T16 mosaicism. Prenatal diagnosis confirmed 5 true positive cases and 9 false positive cases. Among the 5 true positive cases, 3 cases had ultrasound abnormalities. All of the 9 false positive cases continued their pregnancies. The newborns who were from these 9 false positive cases except 1 case (case 7) had low birth weights (< 2.5 kg) and there were also 2 premature deliveries.”
- “Conclusion: NIPT serves as a fast and early prenatal screening method, giving clues to chromosome abnormalities and providing guidance for managing pregnancy. Confined placental mosaicism in 16 pregnancies may be at higher risk for preterm delivery.”