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.”
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.
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.”
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.”
Application of various genetic analysis techniques for detecting two rare cases of 9p duplication mosaicism during prenatal diagnosis.20231130160225
Application of various genetic analysis techniques for detecting two rare cases of 9p duplication mosaicism during prenatal diagnosis.
Zhang S, Zhou Y, Xiao G, Qiu X. Mol Genet Genomic Med. 2023;e2229. doi:10.1002/mgg3.2229 Open access: Learn more
Tags: Case Report / Case Series, 2023, China, RAAs, CNVs
- “Herein, we describe the clinical phenotypes and various prenatal diagnostic processes used for two rare cases of 9p duplication mosaicism [initially suspected based on NIPT results] and review the prior literature in the field to evaluate the merits of different methods for diagnosing mosaic 9p duplication.”
- “This study demonstrated the potential of using NIPT to suggest 9p duplication in early pregnancy.”
Evaluation of the clinical effects of non-invasive prenatal screening for diseases associated with aneuploidy and copy number variation.20231130160135
Evaluation of the clinical effects of non-invasive prenatal screening for diseases associated with aneuploidy and copy number variation.
Zhu S, Jia C, Hao S, et al. Mol Genet Genomic Med. 2023;e2200. doi:10.1002/mgg3.2200 Open Access: Learn more
Tags: Clinical Experience / Clinical Utility, 2023, China, RAAs, CNVs
- Prospective study of over 25,000 pregnant women who had NIPS-PLUS. 415 individuals had positive results, including 275 indicating aneuploidy and 140 indicating microdeletion/microduplication syndromes (MMS).
- Following amniocentesis, 188 were confirmed as true positives (including 41 cases of RATs and 57 MMS).
- PPV was 25.63% for RATs, PPV was 44.66% for CNVs <5 Mb, PPV was 29.73% for CNVs >5 Mb.
A Case of Maternal Uniparental Disomy of Chromosome 6 with Intrauterine Growth Restriction.20231130155834
A Case of Maternal Uniparental Disomy of Chromosome 6 with Intrauterine Growth Restriction.
Feng L, Ma Y, Xu Y. Altern Ther Health Med. 2023;29(7):447-449. Open Access: Learn more
Tags: Case Report / Case Series, 2023, China, RAAs
- NIPT result of trisomy 6. FISH (fluorescence in situ hybridization) and whole exome sequencing on amniocytes revealed no abnormalities. CMA on amniocytes detected UPD 6. Ultrasound at 28 weeks gestation showed intrauterine growth restriction.
Prenatal diagnosis of a case with complete and uniform tetrasomy 12p by the utility of noninvasive prenatal testing.20231130155453
Prenatal diagnosis of a case with complete and uniform tetrasomy 12p by the utility of noninvasive prenatal testing.
Zhang F, Yin T, Tang X, et al. J Assist Reprod Genet. 2023;40(9):2233-2240. doi:10.1007/s10815-023-02896-8.
Tags: Case Report / Case Series, 2023, China, CNVs
- “NIPT results showed increased signal from chromosome 12p. Subsequent prenatal diagnostic testing by karyotype revealed 47,XY,+i(12p), and CMA displayed four copies of 12p: 12p13.33-12p11.1(173786_34835641)×4. The CNV-seq results of the fetal skin and the fetal side of placenta showed four copies of 12p13.33-p11 and an estimated chimeric duplication of 34.08 Mb (chimerism ratio: 10%) in 12p13.33-p11, respectively. However, no abnormality was detected by CNV-seq at the maternal side of placenta. Our findings suggest that a positive signal from chromosome 12p on NIPT should raise suspicion for PKS [Pallister-Killian syndrome]. With the wide application of NIPT, the true positive of incidental finding is expected to increase.”