Residual risk for clinically significant copy number variants in low-risk pregnancies, following exclusion of noninvasive prenatal screening-detectable findings.20221130172802
Residual risk for clinically significant copy number variants in low-risk pregnancies, following exclusion of noninvasive prenatal screening-detectable findings.
Maya I, Salzer Sheelo L, Brabbing-Goldstein D, et al. Am J Obstet Gynecol. 2022;226(4):562.e1-562.e8. doi:10.1016/j.ajog.2021.11.016. Open Access: Learn more
Tags: Clinical Experience / Clinical Utility, 2022, Israel, RAAs, CNVs
- “Of the 7235 pregnancies, clinically significant copy number variants were demonstrated in 87 cases (1.2%). The residual risk following theoretically normal noninvasive prenatal screening was 1.07% (1/94) for 3-noninvasive prenatal screening, 0.78% (1/129) for 5- noninvasive prenatal screening, 0.74% (1/136) for 5- noninvasive prenatal screening including common microdeletions, and 0.68% (1/147) for genome-wide noninvasive prenatal screening.”
- “Conclusion: The residual risk of clinically significant copy number variants in pregnancies without structural sonographic anomalies is appreciable and depends on the noninvasive prenatal screening extent and maternal age.”
Clinical application of expanded noninvasive prenatal testing for fetal chromosome abnormalities in a cohort of 39,580 pregnancies.20221130164523
Clinical application of expanded noninvasive prenatal testing for fetal chromosome abnormalities in a cohort of 39,580 pregnancies.
Chen Y, Lu L, Zhang Y, et al. Am J Med Genet A. 2022;188(5):1426-1434. doi:10.1002/ajmg.a.62657.
Tags: Clinical Experience / Clinical Utility, 2022, China, CNVs
- Retrospective study of 39,580 pregnancies with NIPT-Plus. 511 (1.3%) had screen positive results of which 87.7% (448/511) had invasive prenatal diagnosis.
- PPVs were 86.0% for T21, 79.5% for T18, and 54.5% for T13.
- PPV for CNVs was 41.7% (15.0% for CNVs <5 Mb, 25.0% for CNVs 5–10 Mb, and 50.0% for CNVs >10 Mb).
Clinical utility of expanded NIPT for chromosomal abnormalities and etiology analysis of cytogenetic discrepancies cases.20221130164439
Clinical utility of expanded NIPT for chromosomal abnormalities and etiology analysis of cytogenetic discrepancies cases.
Hu Y, Liu W, He G, Xu J, Peng Y, Wang J. J Assist Reprod Genet. 2022;39(1):267-279. doi:10.1007/s10815-021-02351-6. Learn more
Tags: Clinical Experience / Clinical Utility, 2022, China, RAAs, CNVs
- Study cohort of 2,139 singleton pregnancies having expanded NIPT.
- PPV for T21 and T18 was 100% for both conditions. PPV for CNVs >10 Mb and 5–10 Mb was 42.8% and 16.7%, respectively.
Initial Clinical Experience with NIPT for Rare Autosomal Aneuploidies and Large Copy Number Variations.20221130164354
Initial Clinical Experience with NIPT for Rare Autosomal Aneuploidies and Large Copy Number Variations.
Harasim T, Neuhann T, Behnecke A, Stampfer M, Holinski-Feder E, Abicht A. J Clin Med. 2022;11(2):372. Published 2022 Jan 13. doi:10.3390/jcm11020372. Open Access: https://www.mdpi.com/2077-0383/11/2/372.
Tags: Clinical Experience / Clinical Utility, 2022, Germany, RAAs, CNVs
- Study describes GW-NIPT results on 3664 patient samples at a single genetics center.
- “RAAs and CNVs (>7 Mb) were detected in 0.5%, and 0.2% of tested cases, respectively. Follow up on pregnancies with an NIPT-positive result for RAA revealed signs of placental insufficiency or intra-uterine death in 50% of the cases and normal outcome at the time of birth in the other 50% of cases. We showed that CNV testing by NIPT allows for the detection of unbalanced translocations and relevant maternal health conditions.”
- “NIPT for aneuploidies of all autosomes and large CNVs of at least 7 Mb has a low “non-reportable”-rate (<0.2%) and allows the detection of additional conditions of clinical significance…Our results support previous work showing that NIPT detection of CNVs has clinical value that may extend beyond the detection of fetal anomalies.”
Pregnancy outcomes of rare autosomal trisomies results in non-invasive prenatal screening: clinical follow-up data from a single tertiary centre.20221130164310
Pregnancy outcomes of rare autosomal trisomies results in non-invasive prenatal screening: clinical follow-up data from a single tertiary centre.
Lin Y, Hu P, Li H, Luo C, Liang D, Xu Z. J Cell Mol Med. 2022;26(8):2251-2258. doi:10.1111/jcmm.17245. Open Access: https://onlinelibrary.wiley.com/doi/10.1111/jcmm.17245.
Tags: Clinical Experience / Clinical Utility, 2022, China, RAAs
- “151 (0.24%) RATs results were reported among 62,752 NIPS examinations. Sixty-five women chose to undergo amniocentesis for confirmation, which revealed 3 cases of true fetal mosaicism for RATs and a positive predictive value of 4.6% (3/65). Among the 139 women with available outcomes, 26 (18.7%) had a preterm birth, 10 (7.2%) underwent pregnancy termination because of fetal defects and 5 (3.6%) had miscarriages. Interestingly, compared with the control group, pregnancies in which NIPS revealed trisomy 16 (T16), T22, T9 and T2 were at higher risk of adverse outcomes, including preterm birth, miscarriage and ultrasound abnormalities. However, the risk of adverse outcomes was comparable between the control group and pregnancies with positive results of T7, T3, T8 and T20.”
- “In summary, the risk of adverse pregnancy outcomes was higher in women with specific RATs-positive NIPS results. Pregnancies with T16, T22, T9 and T2 results, even if false-positive, should be considered high-risk pregnancies.”
Noninvasive prenatal testing: How far can we reach detecting fetal copy number variations.20221130164229
Noninvasive prenatal testing: How far can we reach detecting fetal copy number variations.
Mayo S, Gómez-Manjón I, Atencia G, Moreno-Izquierdo A, Escribano D, Fernández-Martínez FJ. Eur J Obstet Gynecol Reprod Biol. 2022;272:150-155. doi:10.1016/j.ejogrb.2022.03.027.
Tags: Case Report / Case Series, 2022, International, CNVs
- “We report a detection of 44.7 Mb duplication at 11p15.5-p11.2 by NIPT with a fetal fraction (FF) of only 3%. This chromosome abnormality was confirmed after amniocentesis by karyotyping and array comparative genomic hybridization on cultured fetal cells. Further parental investigation showed that the fetal chromosome abnormality was inherited from the mother who was a carrier of a balanced translocation 46,XX,t(11;X)(p11.2;q28). This case highlights the importance of expanded NIPT in the detection of fetal segmental aneuploidy. NIPT together with complementary studies can lead to the detection of parental chromosome rearrangement despite a low FF, which can impact the couple’s reproductive plans. We also reviewed other cases with chromosome rearrangement, detected by NIPT, derived from a parental reciprocal translocation.”
Genome wide noninvasive prenatal testing detects microduplication of the distal end of chromosome 15 in a fetus: a case report.20221130164153
Genome wide noninvasive prenatal testing detects microduplication of the distal end of chromosome 15 in a fetus: a case report.
Sahinbegovic H, Andres S, Langer-Freitag S, et al. Mol Cytogenet. 2022;15(1):16. Published 2022 Apr 2. doi:10.1186/s13039-022-00592-3. Open Access: Learn more
Tags: Case Report / Case Series, 2022, International, CNVs
- NIPT detected a 10.34 Mb terminal 15q dup (15q26.1q26.3), subsequently confirmed using karyotype, microarray, and FISH (fluorescence in situ hybridization). Karyotype results indicated an unbalanced translocation between chromosomes 15 and 18 with a final karyotype of 46,XX,der(18)t(15;18)(q26.2;q23)dn.
Prenatal diagnosis and genetic counseling of a uniparental isodisomy of chromosome 8 with no phenotypic abnormalities.20221130164053
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 pregnancies20221130164003
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 study20221130163901
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.”