Mosaic trisomy 16 at amniocentesis in a pregnancy associated with positive non-invasive prenatal testing for trisomy 16, placental trisomy 16, intrauterine growth restriction, intrauterine fetal death, cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes, and prenatal progressive decrease of the aneuploid cell line.
CP, Wu FT, Chen YY, et al. Taiwan J Obstet Gynecol. 2023;62(4):597-601. doi:10.1016/j.tjog.2023.05.008. Open Access: Learn more
Tags: Case Report / Case Series, 2023, Taiwan, RAAs
“Mosaic trisomy 16 at amniocentesis can be associated with positive NIPT for trisomy 16, placental trisomy 16, IUGR [intrauterine growth restriction], IUFD [intrauterine fetal demise], cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes, and prenatal progressive decrease of the aneuploid cell line.”
Overview of Noninvasive Prenatal Testing (NIPT) for the Detection of Fetal Chromosome Abnormalities; Differences in Laboratory Methods and Scope of Testing.
Benn P, Cuckle H. Clin Obstet Gynecol. 2023;66(3):536-556. doi:10.1097/GRF.0000000000000803.
Tags: Review / Meta-Analysis, 2023, International, RAAs, CNVs
- “Although nearly all noninvasive prenatal testing is currently based on analyzing circulating maternal cell-free DNA, the technical methods used vary considerably. We review the different methods. Based on validation trials and clinical experience, there are mostly relatively small differences in screening performance for trisomies 21, 18, and 13 in singleton pregnancies. Recent reports show low no-call rates for all methods, diminishing its importance when choosing a laboratory. However, method can be an important consideration for twin pregnancies, screening for sex chromosome abnormalities, microdeletion syndromes, triploidy, molar pregnancies, rare autosomal trisomies, and segmental imbalances, and detecting maternal chromosome abnormalities.”
Pregnant women’s and policymakers’ preferences for the expansion of noninvasive prenatal screening: A discrete choice experiment approach study.
Nguyen HM, Baradaran M, Daigle G, Nshimyumukiza L, Guertin JR, Reinharz D. Health Sci Rep. 2023;6(8):e1516. Published 2023 Aug 23. doi:10.1002/hsr2.1516. Open Access: Learn more
Tags: Patient Perspectives, Health Care Provider Perspectives, 2023, Canada, RAAs, CNVs
- 272 pregnant women and 24 policymakers completed the questionnaire.
- In the pregnant women group, all seven attributes were statistically significant, denoting their importance, with pregnant women placing the greatest importance on cost related to the test, followed by test performance, and degree of test result certainty.
- In the policymakers group, three attributes were statistically significant: test performance, degree of test result certainty regarding the severity of the disability, and cost related to the test.
Expansion of non-invasive prenatal screening to the screening of 10 types of chromosomal anomalies: a cost-effectiveness analysis.
Soukkhaphone B, Baradaran M, Nguyen BD, et al. BMJ Open. 2023;13(8):e069485. Published 2023 Aug 30. doi:10.1136/bmjopen-2022-069485. Open Access: Learn more
Tags: Health Economics, 2023, Canada, RAAs, CNVs
- Based on results of this simulation study, the most effective and most cost-effective option in almost all screening strategies is the one that includes all additional targeted conditions (SCAs, 22q11.2 deletions syndrome, large deletions/duplications >7 Mb and RATs).
- “The acceptability curves show that at a willingness-to-pay of $C50 000 per one additional case detected, the expansion of NIPS-based methods for the detection of all possible additional conditions has a 90% probability of being cost-effective.”
- “Conclusion: From an economic perspective, in strategies that use NIPS as a first-tier screening test, expanding the programmes to detect any considered chromosomal anomalies other than the three common trisomies would be cost-effective. However, the potential expansion of prenatal screening programmes also requires consideration of societal issues, including ethical ones.”
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.
Normal karyotype and no uniparental disomy 7 at amniocentesis in a pregnancy associated with a non-invasive prenatal testing result suspicious of trisomy 7 and a favorable outcome
Normal karyotype and no uniparental disomy 7 at amniocentesis in a pregnancy associated with a non-invasive prenatal testing result suspicious of trisomy 7 and a favorable outcome. Chen CP. Taiwan J Obstet Gynecol. 2023;62(5):782-783. doi:10.1016/j.tjog.2023.07.028. Learn more
- NIPT at 13 weeks revealed a result suspicious of T7. Amniocentesis at 19 weeks revealed a karyotype of 46,XX; parental karyotypes were normal; QF-PCR (quantitative fluorescence polymerase chain reaction) analysis on DNA extracted from uncultured amniocytes and parental bloods excluded UPD7; aCGH (array comparative genomic hybridization) on DNA extracted from uncultured amniocytes revealed the result of arr(1-22,X)x2.
- The neonate manifested growth deficiency, persistent hypoglycemia, and psychomotor developmental delay.
- “In conclusion, we suggest that UPD 7 testing for UPD 7 is necessary during amniocentesis in case of the NIPT result suspicious of trisomy 7.”
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 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.
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.
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.”