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.”
Cell-free DNA test for pathogenic copy number variations: A retrospective study.
Duan HL, Li J, Wang WJ, et al. Taiwan J Obstet Gynecol. 2021;60(6):1066-1071. doi:10.1016/j.tjog.2021.09.018. Open Access: Learn more
Tags: Clinical Experience / Clinical Utility, 2021, Taiwan, CNVs
- Retrospective study of 29 pregnancies with prenatal diagnosis of fetal microdeletion/microduplication syndromes by CMA.
- 24 CNVs were identified by NIPT among the 21 fetuses with pathogenic CNVs, including 20 concordant CNVs and 21 discordant CNVs. Overall detection rate of NIPT for pathogenic CNVs >2 Mb was 69%.
- “Conclusion: Cell-free DNA test exhibited a moderate DR for pathogenic CNVs ＞2 Mb among fetuses with ultrasound abnormalities. Cell-free DNA test could provide an opportunity for early screening before the appearance of abnormalities on fetal ultrasound, while further clinical data and cost-effectiveness assessment are needed.”
Prenatal Identification of Confined Placental Mosaicism in Pregnant Women with Fetal Growth Restriction.
Miyagami K, Shirato N, Izumi M, et al. Reprod Sci. 2022;29(3):896-903. doi:10.1007/s43032-021-00772-3.
Tags: Clinical Experience / Clinical Utility, 2021, Japan, RAAs
- “cfDNA analyses of maternal plasma detected suspected CPM cases with chromosomal aneuploidy or copy number variations in 5 of 40 cases (12.5%). For 4 cases in which the entire placenta consisted of cells with chromosomal abnormalities, fetal growth was severely restricted. CPM can be screened by cfDNA analysis in maternal plasma, accounting for approximately 10% of the causes of moderate or severe FGR [fetal growth restriction], and the higher the proportion of abnormal karyotype cells in the placenta, the more severe the placental dysfunction and FGR.”
Expanding the application of non-invasive prenatal testing in the detection of foetal chromosomal copy number variations.
Wang C, Tang J, Tong K, et al. BMC Med Genomics. 2021;14(1):292. Published 2021 Dec 11. doi:10.1186/s12920-021-01131-6. Open Access: Learn more
Tags: Clinical Experience / Clinical Utility, 2021, China, RAAs, CNVs
- Study of 39,002 women who had NIPT. 473 pregnancies (1.213%) were screen positive for clinically significant fetal chromosome abnormalities by NIPT.
- PPVs for T21, T18, T13, SCA, RATs, and microdeletion/microduplication syndrome cases were 88.89%, 53.33%, 20.00%, 40.22%, 4.88%, and 49.02%, respectively.
- PPVs of CNVs of <5 Mb, 5–10 Mb, and >10 Mb were 54.55%, 38.46%, and 40.00%, respectively.
Three years of clinical experience with a genome-wide cfDNA screening test for aneuploidies and copy-number variants
[published correction appears in Genet Med. 2021 May 6;:]. Soster E, Boomer T, Hicks S, et al. Genet Med. 2021;23(7):1349-1355. doi:10.1038/s41436-021-01135-8. Open Access: Learn more
Tags: Laboratory Performance / Laboratory Experience, Clinical Experience / Clinical Utility, 2021, United States, RAAs, CNVs
- This publication is a retrospective analysis of over 55,000 samples submitted for Expanded NIPT to the laboratory, with diagnostic outcomes available in over 40% of screen positive cases. The publication reports on testing indications, demographics, results, and performance. The authors noted that indications shifted during the 3-year period, with a decrease in referrals for ‘ultrasound findings’ (22.0% to 12.0%) and an increase in referrals of ‘no known high-risk indication’ (3.0% to 16.6%). Of the screen positive results, they reported that 25% would have been missed with NIPT limited to the common aneuploidies. They concluded that, although a broader patient population is using Expanded NIPT, the positivity rates and genome-wide events have remained stable at approximately 5% and 25%, respectively.
Outcome of publicly funded nationwide first-tier noninvasive prenatal screening
Van Den Bogaert K, Lannoo L, Brison N, et al. Genet Med. 2021;23(6):1137-1142. doi:10.1038/s41436-021-01101-4. Open Access: Learn more
Tags: Clinical Experience / Clinical Utility, 2021, Belgium, RAAs, CNVs
- Belgium was the first country to implement and fully reimburse NIPT as a first-tier screening for all pregnant women. In this publication, a consortium comprised of all the Belgian genetic center reports on the clinical experience during a 2-year period of offering Expanded NIPT as a first-tier testing option for all pregnant women. Of the 153,575 pregnancies screened, rare autosomal trisomies and partial deletions/duplications were found in 0.23% and 0.07% of cases, respectively. Invasive diagnostic obstetric procedures decreased by 52%. The authors conclude that their Expanded NIPT approach has been successfully implemented into prenatal care in Belgium and could possibly act as a framework for other countries offering NIPT.
Genome-wide noninvasive prenatal screening for carriers of balanced reciprocal translocations.
Flowers NJ, Burgess T, Giouzeppos O, et al. Genet Med. 2020;22(12):1944-1955. doi:10.1038/s41436-020-0930-2. Open Access: Learn more
Tags: Clinical Experience / Clinical Utility, 2020, Australia, CNVs
- This pilot series comprises a retrospective analysis of GW-NIPS and clinical outcome data from 42 singleton pregnancies where one parent carried a balanced reciprocal translocation. GW-NIPS was performed between August 2015 and March 2018. Inclusion criteria required at least one translocation segment to be ≥15 Mb in size.
- “Forty samples (95%) returned an informative result; 7 pregnancies (17.5%) were high risk for an unbalanced translocation and confirmed after diagnostic testing. The remaining 33 informative samples were low risk and confirmed after diagnostic testing or normal newborn physical exam. Test sensitivity of 100% (95% confidence interval [CI]: 64.6-100%) and specificity of 100% (95% CI: 89.6-100%) were observed for this pilot series.”
- “We demonstrate that GW-NIPS is a potential option for a majority of reciprocal translocation carriers. Further confirmation of this methodology could lead to adoption of this noninvasive alternative.”
TRIDENT-2: National Implementation of Genome-wide Non-invasive Prenatal Testing as a First-Tier Screening Test in the Netherlands
van der Meij KRM, Sistermans EA, Macville MVE, et al. Am J Hum Genet. 2019;105(6):1091-1101. doi:10.1016/j.ajhg.2019.10.005. Open Access: Learn more
Tags: Clinical Experience / Clinical Utility, 2019, Netherlands, RAAs, CNVs
- This publication describes results from a nationwide implementation study in the Netherlands that examined the use of NIPT as a first-tier test offered to all pregnant women, with the option to have findings beyond trisomies 21, 18, and 13 reported based on patient request. 78% of pregnant women chose to have these additional findings reported to them.
Clinical utility of noninvasive prenatal screening for expanded chromosome disease syndromes
Liang D, Cram DS, Tan H, et al. Genet Med. 2019;21(9):1998-2006. doi:10.1038/s41436-019-0467-4. Open Access: Learn more
Tags: Clinical Experience / Clinical Utility, 2019, China, RAAs, CNVs
- This publication examined the clinical performance of Expanded NIPT for both aneuploidy and genome-wide microdeletion/microduplication syndromes in an all-risk pregnancy population. A cohort of 94,085 patients with singleton pregnancies were prospectively enrolled. This Expanded NIPT detected a clinically significant fetal chromosome abnormality in 1.2% of samples and calculated the respective PPVs for the screen positive abnormalities.
Perinatal outcomes following cell-free DNA screening in >32 000 women: Clinical follow-up data from a single tertiary center
Liang D, Lin Y, Qiao F, et al. Prenat Diagn. 2018;38(10):755-764. doi:10.1002/pd.5328. Open Access: Learn more
Tags: Clinical Experience / Clinical Utility, 2018, China, RAAs, CNVs
- This publication retrospectively reviewed the follow-up information from 32,431 cases at a single tertiary care center offering Expanded NIPT.