Rare autosomal trisomies detected by non-invasive prenatal testing: an overview of current knowledge.
Lannoo L, van Straaten K, Breckpot J, et al. Eur J Hum Genet. 2022;30(12):1323-1330. doi:10.1038/s41431-022-01147-1.
Tags: Review / Meta-Analysis, 2022, International, RAAs
- “In this review we reviewed the current knowledge of the most common RATs. We compiled clinical relevant parameters such as incidence, meiotic or mitotic origin, the risk of fetal (mosaic) aneuploidy, clinical manifestations of fetal mosaicism for a RAT, the effect of confined placental mosaicism on placental function and the risk of uniparental disomy (UPD). Finally, we identified gaps in the knowledge on RATs and highlight areas of future research. This overview may serve as a first guide for prenatal management for each of these RATs.”
Clinical evaluation of non-invasive prenatal screening for the detection of fetal genome-wide copy number variants.
Wang W, Lu F, Zhang B, Zhou Q, Chen Y, Yu B. Orphanet J Rare Dis. 2022;17(1):253. Published 2022 Jul 8. doi:10.1186/s13023-022-02406-6. Open Access: Learn more
Tags: Clinical Experience / Clinical Utility, 2022, China, CNVs
- Among 50,972 NIPT results, 212 cases were positive for CNVs. 96 women subsequently had amniocentesis with CMA.
- 37/96 cases were confirmed true positives for fetal CNVs (PPV 38.5%).
- PPVs were 48.7% for CNVs <3 Mb, 41.4% for CNVs 3~5 Mb, 42.9% for CNVs 5~10 Mb, and 14.3% for CNVs >10 Mb.
- Chromosomal location may be a main factor influencing PPV.
Positive predictive value estimates for noninvasive prenatal testing from data of a prenatal diagnosis laboratory and literature review.
Liu S, Yang F, Chang Q, et al. Mol Cytogenet. 2022;15(1):29. Published 2022 Jul 6. doi:10.1186/s13039-022-00607-z. Open Access: Learn more
Tags: Laboratory Performance / Laboratory Experience, 2022, China, RAAs, CNVs
- Retrospective study of women referred for invasive prenatal diagnosis following a positive NIPT results.
- PPVs for trisomies 21, 18, and 13 were 86.1%, 57.8%, and 25.0%, respectively.
- PPVs for rare chromosomal abnormalities and and CNVs were 17.0% and 40.4%, respectively.
- A significant increase in true positives was seen in the high-risk groups compared to low- and moderate-risk groups.
Validity and Utility of Non-Invasive Prenatal Testing for Copy Number Variations and Microdeletions: A Systematic Review.
Zaninović L, Bašković M, Ježek D, Katušić Bojanac A. J Clin Med. 2022;11(12):3350. Published 2022 Jun 10. doi:10.3390/jcm11123350. Open Access: Learn more
Tags: Review / Meta-Analysis, 2022, International, CNVs
- 32 articles met the criteria for this systematic review of the analytical and clinical performance of NIPT for CNVs and microdeletions.
- “The reported sensitivity of the applied tests ranged from 20% to 100%, the specificity from 81.62% to 100%, and the PPV from 3% to 100% for cases with diagnostic or clinical follow-up information. No confirmatory analysis was available in the majority of cases with negative screening results, and, therefore, the NPVs [negative predictive values] could not be determined.”
Prenatal diagnosis of trisomy 8 mosaicism, initially identified by cffDNA screening.
Hu J, Yan K, Jin P, Yang Y, Sun Y, Dong M. Mol Cytogenet. 2022;15(1):39. Published 2022 Sep 1. doi:10.1186/s13039-022-00616-y. Open Access: Learn more
Tags: Case Report / Case Series, 2022, China, RAA
- Case study where NIPT identified trisomy 8 at 17 weeks with mosaic trisomy 8 confirmed by diagnostic testing.
Whole genome non-invasive prenatal testing in prenatal screening algorithm: clinical experience from 12,700 pregnancies.
Baranova EE, Sagaydak OV, Galaktionova AM, et al. BMC Pregnancy Childbirth. 2022;22(1):633. Published 2022 Aug 9. doi:10.1186/s12884-022-04966-8. Open Access: Learn more
Tags: Clinical Experience / Clinical Utility, 2022, Russia, RAAs, CNVs
- “258 (2.0%) samples with positive NIPT results were detected including 126 cases of trisomy 21 (T21), 40 cases of T18, 12 cases of T13, 41 cases of sex chromosome aneuploidies (SCAs) and 39 cases of rare autosomal aneuploidies (RAAs) and significant copy number variations (CNVs).”
- The most common RAAs were T7 (n=6), T16 (n=4), T8 (n=3) and T22 (n=3).
PPVs were 98.26% for T12, 91.67% for T18/13, 57.14% for SCAs, and 44.83% for RAAs/CNVs.
The predictive value of prenatal cell-free DNA testing for rare autosomal trisomies: a systematic review and meta-analysis.
Acreman ML, Bussolaro S, Raymond YC, Fantasia I, Rolnik DL, Da Silva Costa F. Am J Obstet Gynecol. 2023;228(3):292-305.e6. doi:10.1016/j.ajog.2022.08.034.
Tags: Review / Meta-Analysis, 2022, International, RAAs
- Systematic review and meta-analysis to determine the PPV of cfDNA screening for RATs. 31 studies, representing 1703 women were included.
- Pooled PPV for RATs was 11.46%. Statistical heterogeneity was high. Insufficient data to provide accurate ascertainment of sensitivity and specificity because Confirmatory testing was mostly only offered to women with high-risk results; therefore, there was insufficient data to determine sensitivity and specificity.
Multisite assessment of the impact of cell-free DNA-based screening for rare autosomal aneuploidies on pregnancy management and outcomes.
Mossfield T, Soster E, Menezes M, et al. Front Genet. 2022;13:975987. Published 2022 Aug 29. doi:10.3389/fgene.2022.975987. Open Access: Learn more
Tags: Clinical Experience / Clinical Utility, 2022, International, RAAs, Consortium Publication
- “Here, we describe a multi-cohort, global retrospective study that looked at the clinical outcomes of cases with a high-risk cfDNA screening result for a RAA. Our study cohort included a total of 109 cases from five different sites, with diagnostic outcome information available for 68% (74/109) of patients. Based on confirmatory diagnostic testing, we found a concordance rate of 20.3% for presence of a RAA (15/74) in our study population. Pregnancy outcome was also available for 77% (84/109) of cases in our cohort. Many of the patients experienced adverse pregnancy outcomes, including intrauterine fetal demise, fetal growth restriction, and preterm birth. These adverse outcomes were observed both in patients with fetal or placental confirmation of the presence of a RAA, as well as patients that did not undergo fetal and/or placental diagnostic testing.”
- “In addition, we have proposed some suggestions for pregnancy management and counseling considerations for situations where a RAA is noted on a cfDNA screen.”
- “In conclusion, our study has shown that genome-wide cfDNA screening for the presence of rare autosomal aneuploidies can be beneficial for both patients and their healthcare practitioners. This can provide a possible explanation for an adverse pregnancy outcome or result in a change in pregnancy management, such as increased monitoring for adverse outcomes.”
Cell-free DNA screening for rare autosomal trisomies and segmental chromosome imbalances.
Raymond YC, Fernando S, Menezes M, et al. Prenat Diagn. 2022;42(11):1349-1357. doi:10.1002/pd.6233. Open Access: Learn more
Tags: Clinical Experience / Clinical Utility, 2022, Australia, RAAs, CNVs
- “Among 23,857 women screened, there were 93 high-risk results for RATs (0.39%) and 82 for SIs [structural imbalances] (0.34%). The PPVs were 3.8% (3/78, 95% CI 0.8%-10.8%) for RATs and 19.1% (13/68, 95% CI 10.6%-30.5%) for SIs. If fetuses with structural anomalies were also counted as true-positive cases, the PPV for RATS increased to 8.5% (7/82, 95% CI 3.5%-16.8%). Among 85 discordant cases with birth outcomes available (65.4%), discordant positive RATs had a significantly higher proportion of infants born below the 10th and 3rd birthweight percentiles than expected (19.6% (p = 0.022) and 9.8% (p = 0.004), respectively), which was not observed in the SI group (2.9% < 10th (p = 0.168) and 0.0% <3rd (p = 0.305)).”
Case Report: How whole-genome sequencing-based cell-free DNA prenatal testing can help identify a marker chromosome.
Kleinfinger P, Brechard M, Luscan A, et al. Front Genet. 2022;13:926290. Published 2022 Sep 26. doi:10.3389/fgene.2022.926290. Open Access Learn more
Tags: Case Report / Case Series, 2022, France, CNVs
- GW-NIPT rapidly characterized supernumerary marker chromosomes for a patient in a time- and cost-effective manner – a pericentromeric 29 Mb dup (20) (p13q11.21) was identified and then confirmed by targeted FISH (fluorescence in situ hybridization).