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.
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.
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.
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.”
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).
Clinical evaluation of non-invasive prenatal screening for the detection of fetal genome-wide copy number variants.
Wang W, Lu F, Zhang B, Zhou Q, Chen Y, Yu B. Orphanet J Rare Dis. 2022;17(1):253. Published 2022 Jul 8. doi:10.1186/s13023-022-02406-6. Open Access: Learn more
Tags: Clinical Experience / Clinical Utility, 2022, China, CNVs
- Among 50,972 NIPT results, 212 cases were positive for CNVs. 96 women subsequently had amniocentesis with CMA.
- 37/96 cases were confirmed true positives for fetal CNVs (PPV 38.5%).
- PPVs were 48.7% for CNVs <3 Mb, 41.4% for CNVs 3~5 Mb, 42.9% for CNVs 5~10 Mb, and 14.3% for CNVs >10 Mb.
- Chromosomal location may be a main factor influencing PPV.
Positive predictive value estimates for noninvasive prenatal testing from data of a prenatal diagnosis laboratory and literature review.
Liu S, Yang F, Chang Q, et al. Mol Cytogenet. 2022;15(1):29. Published 2022 Jul 6. doi:10.1186/s13039-022-00607-z. Open Access: Learn more
Tags: Laboratory Performance / Laboratory Experience, 2022, China, RAAs, CNVs
- Retrospective study of women referred for invasive prenatal diagnosis following a positive NIPT results.
- PPVs for trisomies 21, 18, and 13 were 86.1%, 57.8%, and 25.0%, respectively.
- PPVs for rare chromosomal abnormalities and and CNVs were 17.0% and 40.4%, respectively.
- A significant increase in true positives was seen in the high-risk groups compared to low- and moderate-risk groups.
Prenatal diagnosis of trisomy 8 mosaicism, initially identified by cffDNA screening.
Hu J, Yan K, Jin P, Yang Y, Sun Y, Dong M. Mol Cytogenet. 2022;15(1):39. Published 2022 Sep 1. doi:10.1186/s13039-022-00616-y. Open Access: Learn more
Tags: Case Report / Case Series, 2022, China, RAA
- Case study where NIPT identified trisomy 8 at 17 weeks with mosaic trisomy 8 confirmed by diagnostic testing.
A retrospective single-center analysis of prenatal diagnosis and follow-up of 626 chinese patients with positive non-invasive prenatal screening results.
Bu X, Zhou S, Li X, et al. Front Genet. 2022;13:965106. Published 2022 Sep 19. doi:10.3389/fgene.2022.965106. Open Access: Learn more
Tags: Clinical Experience / Clinical Utility, 2022, China, RAAs, CNVs
- Study of 626 women with positive NIPT results.
- PPVs were 81.13% for T21, 37.93% for T18, 18.42% for T13, 48.83% for SCAs, 18.37% for RATs, and 41.67% for microdeletion and microduplication syndromes (MMS).
- “Additional reporting of RATs and MMS with routine NIPS that only detects T21/T18/T13 and SCAs can yield more accurate diagnoses.”
Comparison of noninvasive prenatal screening for defined pathogenic microdeletion/microduplication syndromes and nonsyndromic copy number variations: a large multicenter study.
Yang L, Bu G, Ma Y, Zhao J, Rezak J, La X. J Comp Eff Res. 2022;11(17):1277-1291. doi:10.2217/cer-2022-0088. Open Access: Learn more
Tags: Clinical Experience / Clinical Utility, 2022, China, CNVs
- Retrospective study of over 19,000 pregnancies with NIPT.
- “The positive predictive value (PPV) of CNV-seq for all types of CNV detected by NIPT was 35.4%, with PPVs of 61.5 and 27.6% for pathogenic MMSs [microdeletion/microduplication syndromes] and nonsyndromic CNVs, respectively. PPVs for NIPT showed different values depending on gestational characteristics, with the highest PPV for NIPT in the group with increased nuchal thickness (66.7%) and for the abnormal ultrasound group (57.1%). CNVs ≤5 Mb with normal ultrasound findings were generally associated with a healthy fetus.”