Prenatal diagnosis and genetic counseling of a uniparental isodisomy of chromosome 8 with no phenotypic abnormalities.
Yu C, Tian Y, Qi L, Wang B. Mol Cytogenet. 2022;15(1):18. Published 2022 Apr 26. doi:10.1186/s13039-022-00594-1. Open Access: Learn more
Tags: Case Report / Case Series, 2022, China, RAA
- Report of a case with NIPT results positive for trisomy 8. Amniocentesis was performed and CMA results were arr 8p23.3p12(168484_29427840) ×2 hmz (29.4 Mb region of uniparental isodisomy of chromosome 8).
Systematic evidence-based review: The application of noninvasive prenatal screening using cell-free DNA in general-risk pregnancies
[published correction appears in Genet Med. 2022 Sep;24(9):1992]. Rose NC, Barrie ES, Malinowski J, et al. Genet Med. 2022;24(7):1379-1391. doi:10.1016/j.gim.2022.03.019. Open Access: Learn more
Tags: Review, 2022, International, RAAs, CNVs
- 87 studies met inclusion criteria for this systematic evidence review, evaluating NIPT performance in a general-risk population.
- Performance for RATs and CNVs was variable and poorer than for common trisomies. For RATs, this is likely related to the rarity of RATs and insufficient data to develop a method that can distinguish between clinically significant RATs present in the fetus versus CPM.
- “Reported overall sensitivity to detect CNVs ranged from 69.44% to 80.56%. When stratified by CNV size, in general, the sensitivity to detect larger CNVs was better than for detecting smaller CNVs. The sensitivity to detect CNVs larger than 5 megabases (Mb) was >90%, whereas for those smaller than 5 Mb, it was 68.42%.”
- NIPT is the only laboratory-based prenatal screen that can identify SCAs, RATs, and CNVs.
Clinical impact of additional findings detected by genome-wide non-invasive prenatal testing: Follow-up results of the TRIDENT-2 study
[published correction appears in Am J Hum Genet. 2022 Jul 7;109(7):1344]. van Prooyen Schuurman L, Sistermans EA, Van Opstal D, et al. Am J Hum Genet. 2022;109(6):1140-1152. doi:10.1016/j.ajhg.2022.04.018. Open Access: Learn more
Tags: Clinical Experience / Clinical Utility, 2022, Netherlands, RAAs, CNVs
- “Between April 2017 and April 2019, additional findings were detected in 402/110,739 pregnancies (0.36%). For 358 cases, the origin was proven to be either fetal (n = 79; 22.1%), (assumed) confined placental mosaicism (CPM) (n = 189; 52.8%), or maternal (n = 90; 25.1%). For the remaining 44 (10.9%), the origin of the aberration could not be determined. Most fetal chromosomal aberrations were pathogenic and associated with severe clinical phenotypes (61/79; 77.2%). For CPM cases, occurrence of pre-eclampsia (8.5% [16/189] vs 0.5% [754/159,924]; RR 18.5), and birth weight <2.3rd percentile (13.6% [24/177] vs 2.5% [3,892/155,491]; RR 5.5) were significantly increased compared to the general obstetric population. Of the 90 maternal findings, 12 (13.3%) were malignancies and 32 (35.6%) (mosaic) pathogenic copy number variants, mostly associated with mild or no clinical phenotypes.”
- “In conclusion, about one in every 275 women in a general obstetric population opting for GW-NIPT receives an additional finding. The majority of additional findings identified by GW-NIPT have clinical impact. Most fetal chromosomal aberrations are pathogenic and associated with severe clinical phenotypes. (Assumed) CPM is significantly associated with adverse perinatal outcomes, requiring tailored obstetric care.”
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.”
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.
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)).”