Clinical impacts of genome-wide noninvasive prenatal testing for rare autosomal trisomy.20231130161826
Clinical impacts of genome-wide noninvasive prenatal testing for rare autosomal trisomy.
Xiang J, Li R, He J, et al. Am J Obstet Gynecol MFM. 2023;5(1):100790. doi:10.1016/j.ajogmf.2022.100790.
Tags: Clinical Experience / Clinical Utility, 2023, China, RAAs
- “Results: Overall, 154 rare autosomal trisomies were identified in 89,242 pregnancies (0.17%) through noninvasive prenatal testing. In the 120 cases in which cytogenetic and molecular investigations were carried out, the rare autosomal trisomies were found to originate from true fetal mosaicism (n=5), uniparental disomy (n=5), maternal mosaic trisomy (n=3), maternal malignancy (n=1), and confined placental mosaicism (n=106). Clinical follow-up showed that 40% of all rare autosomal trisomy cases had adverse perinatal outcomes. In women with false-positive noninvasive prenatal testing results originating from confined placental mosaicism, the frequency of adverse perinatal outcomes was 26%. More importantly, the placental mosaicism ratio revealed by noninvasive prenatal testing was significantly higher in women who experienced adverse perinatal outcomes than those who did not (0.688 vs 0.332; P<.001).”
- “Conclusion: Women with noninvasive prenatal testing results indicative of rare autosomal trisomies are at risk of adverse perinatal outcomes, and that risk can be stratified using chromosomes and the mosaicism ratio revealed by noninvasive prenatal testing. Our data are valuable for obstetrical caregivers advising a patient with a noninvasive prenatal testing result indicative of a rare autosomal trisomy and a false-positive diagnosis and for managing risks during pregnancy.”
Experiences of pregnant women with genome-wide non-invasive prenatal testing in a national screening program.20231130161659
Experiences of pregnant women with genome-wide non-invasive prenatal testing in a national screening program.
van der Meij KRM, van de Pol QYF, Bekker MN, et al. Eur J Hum Genet. 2023;31(5):555-561. doi:10.1038/s41431-022-01248-x. Open Access: Learn more
Tags: Patient Perspectives, 2023, Netherlands, RAAs, CNVs
- A pre-and post-test questionnaire was completed by 473 women choosing between targeted NIPT and GW-NIPT through the Dutch TRIDENT-2 study.
- “Most respondents (90.4%) were glad to have been offered the choice between GW-NIPT and targeted NIPT; 76.5% chose GW-NIPT. Main reasons to choose GW-NIPT were ‘wanting as much information as possible regarding the child’s health’ (38.6%) and ‘to be prepared for everything’ (23.8%). Main reasons to choose targeted NIPT were ‘avoiding uncertain results/outcomes’ (33.7%) and ‘not wanting to unnecessarily worry’ (32.6%). Nearly all respondents received a low-risk NIPT result (98.7%). No differences were found in anxiety between women choosing GW-NIPT and targeted NIPT. Most respondents were favorable toward future prenatal screening for a range of conditions, including life-threatening disorders, mental disabilities, disorders treatable in pregnancy and severe physical disabilities, regardless of their choice for GW-NIPT or targeted NIPT. In conclusion, women who chose first-tier NIPT were satisfied with the choice between GW-NIPT and targeted NIPT, and most women were favorable toward a broader future screening offer.”
Non-invasive prenatal test findings in 41,819 pregnant women: results from a clinical laboratory in southern China.20231130161450
Non-invasive prenatal test findings in 41,819 pregnant women: results from a clinical laboratory in southern China.
Liu S, Chang Q, Yang F, et al. Arch Gynecol Obstet. 2023;308(3):787-795. doi:10.1007/s00404-022-06908-3.
Tags: Clinical Experience / Clinical Utility, 2023, China, RAAs
- “NIPT results were available for 41,819 cases; 691 positive cases were reported. The overall sensitivity for detection of T21, T18, T13, SCA, and RCA [rare chromosome aneuploidies] was 99.21, 100.00, 100.00, 98.55, and 100.00%, and the specificity was 99.95, 99.94, 99.98, 99.69, and 99.92%, respectively. The positive predictive values (PPVs) for detection of T21, T18, T13, SCA, and RCA were 85.62, 45.24, 40.00, 34.17, and 13.51%, respectively.”
Performance of expanded non-invasive prenatal testing for fetal aneuploidies and copy number variations: A prospective study from a single center in Jiangxi province, China.20231130161412
Performance of expanded non-invasive prenatal testing for fetal aneuploidies and copy number variations: A prospective study from a single center in Jiangxi province, China.
Zou Y, Feng C, Qin J, et al. Front Genet. 2023;13:1073851. Published 2023 Jan 13. doi:10.3389/fgene.2022.1073851. Open Access: Learn more
Tags: Clinical Experience / Clinical Utility, 2023, China, RAAs, CNVs
- Of 23,116 patients, 264 (1.14%) had a positive NIPT-Plus result, including 233 aneuploidies and 31 CNVs. 233 (88.26%) patients had invasive diagnostic testing and 136 results were confirmed as true positives, including 2 RATs and 15 CNVs.
- PPVs for RATs and CNVs were 6.67% and 51.72%, respectively.
The role of non-invasive prenatal testing and ultrasound in prenatal screening of fetal chromosomal abnormalities in singleton: a retrospective study.20231130161321
The role of non-invasive prenatal testing and ultrasound in prenatal screening of fetal chromosomal abnormalities in singleton: a retrospective study.
Yuan X, Yong W, Dai L, Wang W, Wu L. Ann Transl Med. 2023;11(2):111. doi:10.21037/atm-22-6343. Open Access: Learn more
Tags: Clinical Experience / Clinical Utility, 2023, China, RAAs, CNVs
- Retrospective study of over 12,000 women who underwent NIPT / expanded NIPT (NIPT-Plus), including 111 cases of positive results.
- PPVs of NIPT/NIPT-Plus for microdeletion/microduplication syndrome (MMS) and RATs were 44.4% and 7.7%, respectively.
- Ultrasound findings of SCAs, MMS, and RATs were relatively mild and included normal findings, soft markers, fetal growth restriction, or polyhydramnios, and the ultrasound findings were similar between false positive and true positive cases.
Prenatal Diagnosis of Uniparental Disomy in Cases of Rare Autosomal Trisomies Detected Using Noninvasive Prenatal Test: A Case of Prader-Willi Syndrome.20231130161219
Prenatal Diagnosis of Uniparental Disomy in Cases of Rare Autosomal Trisomies Detected Using Noninvasive Prenatal Test: A Case of Prader-Willi Syndrome.
Hong DK, Park JE, Kang KM, et al. Diagnostics (Basel). 2023;13(4):580. Published 2023 Feb 4. doi:10.3390/diagnostics13040580. Open Access: Learn more
Tags: Case Report / Case Series, 2023, South Korea, RAAs
- “Overall, six cases were diagnosed with RATs. There was a suspicion of trisomies of chromosomes 7, 8, and 15 in two cases each. However, these cases were confirmed to have a normal karyotype using amniocentesis. In one of six cases, PWS [Prader-Willi syndrome] caused by maternal UPD 15 was diagnosed using MS-PCR and MS-MLPA. We propose that in cases where RAT is detected by NIPT, UPD should be considered following trisomy rescue. Even if amniocentesis confirms a normal karyotype, UPD testing (such as MS-PCR and MS-MLPA) should be recommended for accurate assessment, as an accurate diagnosis can lead to appropriate genetic counseling and improved overall pregnancy management.”
Clinical utility of expanded non-invasive prenatal screening compared with chromosomal microarray analysis in over 8000 pregnancies without major structural anomaly.20231130161128
Clinical utility of expanded non-invasive prenatal screening compared with chromosomal microarray analysis in over 8000 pregnancies without major structural anomaly.
Maya I, Salzer Sheelo L, Brabbing-Goldstein D, et al. Ultrasound Obstet Gynecol. 2023;61(6):698-704. doi:10.1002/uog.26177.
Tags: Clinical Experience / Clinical Utility, 2023, Israel, RAAs, CNVs
- “Conclusions: 5-NIPS and even genome-wide NIPS would miss 63.9% and 54.1% of clinically significant CMA findings [in pregnancies without major structural anomalies], respectively. The added value of 5-NIPS expanded to detect common microdeletions over 5-NIPS is about 0.035%, and the overall added value of genome-wide NIPS aimed at large CNVs is about 0.14%, both much lower compared with the added value of CMA (0.91%).”
Case report: Detection of fetal trisomy 9 mosaicism by multiple genetic testing methods: Report of two cases.20231130161044
Case report: Detection of fetal trisomy 9 mosaicism by multiple genetic testing methods: Report of two cases.
Ma N, Zhu Z, Hu J, et al. Front Genet. 2023;14:1121121. Published 2023 Mar 10. doi:10.3389/fgene.2023.1121121. Open Access: Learn more
Tags: Case Report / Case Series, 2023, China, RAAs
- “The non-invasive prenatal testing (NIPT) results suggested trisomy 9 in two fetuses. Karyotype analysis of amniocytes showed a high level (42%-50%) of mosaicism, and chromosomal microarray analysis (CMA) of uncultured amniocytes showed no copy number variation (CNV) except for large fragment loss of heterozygosity. Ultrasound findings were unmarkable except for small for gestational age… The results [of molecular testing of fetal and placental tissue samples] confirmed the presence of true fetoplacental mosaicism with levels of trisomy 9 mosaicism from 76% to normal in various tissues.”
A Case Report of a Feto-Placental Mosaicism Involving a Segmental Aneuploidy: A Challenge for Genome Wide Screening by Non-Invasive Prenatal Testing of Cell-Free DNA in Maternal Plasma.20231130160922
A Case Report of a Feto-Placental Mosaicism Involving a Segmental Aneuploidy: A Challenge for Genome Wide Screening by Non-Invasive Prenatal Testing of Cell-Free DNA in Maternal Plasma.
De Falco L, Vitiello G, Savarese G, et al. Genes (Basel). 2023;14(3):668. Published 2023 Mar 7. doi:10.3390/genes14030668. Open Access: Learn more
Tags: Case Report / Case Series, 2023, Italy, CNVs
- Case report of 44.1 Mb 4p dup detected by NIPT at 12 weeks. Amniocentesis was performed at 18 weeks; SNP (single nucleotide polymorphism) array found a de novo2 Mb deletion on chromosome 4 near the Wolf-Hirschhorn syndrome critical region and a normal 46,XY karyotype was identified by G-banding analysis.
- Studies of fetal and placental tissue confirmed presence of type VI true fetal mosaicism, with SNP array on 3 placental samples showing different results.
Value of noninvasive prenatal testing in the detection of rare fetal autosomal abnormalities.20231130160845
Value of noninvasive prenatal testing in the detection of rare fetal autosomal abnormalities.
Zhang M, Tang J, Li J, et al. Eur J Obstet Gynecol Reprod Biol. 2023;284:5-11. doi:10.1016/j.ejogrb.2023.03.002. Open Access: Learn more
Tags: Clinical Experience / Clinical Utility, 2023, China, RAAs, CNVs
- “Results: NIPT detected 292 cases (0.36%) with rare autosomal abnormalities among the 81,518 cases sampled. Of these, 140 (0.17%) showed rare autosomal trisomies (RATs), and 102 of these patients agreed to undergo invasive testing. Five cases were true positives, with a positive predictive value (PPV) of 4.90%. Copy number variants (CNV) were detected in 152 samples of the total cases (0.19%), and 95 of the patients involved agreed to the use of CMA. Twenty-nine of these cases were confirmed to be true positive, with a PPV of 30.53%. Detailed follow-up information was obtained in 81 cases from 97 patients with false-positive results for RATs. Thirty-seven of these cases (45.68%) had adverse perinatal outcomes, with a higher incidence of small for gestational age (SGA), intrauterine growth retardation (IUGR), and preterm birth (PTB).”
- “Conclusions: NIPT is not recommended for screening for RATs. However, considering that positive results are associated with an increased risk of IUGR and PTB, additional fetal ultrasound examination should be performed to monitor fetal growth. In addition, NIPT has a reference value in screening for CNVs, especially pathogenic CNVs, but a comprehensive analysis of prenatal diagnosis combined with ultrasound and family history is still needed.”