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.
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%).”
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.”
Late first-trimester ultrasound findings can alter management after high-risk NIPT result.20231130160308
Late first-trimester ultrasound findings can alter management after high-risk NIPT result.
Scott F, Smet ME, Elhindi J, et al. Ultrasound Obstet Gynecol. 2023;10.1002/uog.26272. doi:10.1002/uog.26272
Tags: Clinical Experience / Clinical Utility, 2023, Australia, RAAs, CNVs
- Retrospective study of all cases with NIPT from 3 tertiary providers of obstetric ultrasound using NIPT as a first line screening test over a 4-year period.
- “The LTFU [late first trimester ultrasound] findings significantly altered the PPV of the NIPT result for trisomies 13, 18 and 21, monosomy X (MX) and rare autosomal trisomies (RATs), but not for the other sex chromosomal abnormalities or segmental imbalances (>7 Mb). An abnormal LFTU increased the PPV close to 100% for trisomies 13, 18 and 21, MX and RATs. The magnitude of the PPV alteration was highest for the lethal chromosomal abnormalities.”
- “Conclusions: LTFU after a high-risk NIPT result can alter the PPV of many chromosomal abnormalities, assisting counselling regarding invasive prenatal testing and pregnancy management.”
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.
Evaluation of the clinical utility of extended non-invasive prenatal testing in the detection of chromosomal aneuploidy and microdeletion/microduplication20231101221051
Evaluation of the clinical utility of extended non-invasive prenatal testing in the detection of chromosomal aneuploidy and microdeletion/microduplication
Tian W, Yuan Y, Yuan E, et al. Eur J Med Res. 2023;28(1):304. Published 2023 Aug 30. doi:10.1186/s40001-023-01285-2. Learn more
Tags: Clinical Experience / Clinical Utility, 2023, China, RAAs, CNVs
- With NIPT-PLUS, the detection sensitivity for RATs was 80% (4/5) and PPV for RATs was 50%.
- Detection rate of NIPT-PLUS for microdeletion/microduplication syndrome (MMS) was 63.86%. The larger the MMS fragment, the higher the NIPT-PLUS detection sensitivity.
- Authors conclude that NIPT-PLUS has a high sensitivity for detecting aneuploidy and CNVs > 5Mb. CPM and fetal mosaicism are key factors leading to false negatives. Maternal chromosomal abnormalities and CPM are key factors leading to false positives. Genetic counseling before and after NIPT-PLUS is important.
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.”