Clinical application of expanded noninvasive prenatal testing for fetal chromosome abnormalities in a cohort of 39,580 pregnancies.20221130164523

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.20221130164439

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.20221130164354

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.20221130164310

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.”
Clinical impact of additional findings detected by genome-wide non-invasive prenatal testing: Follow-up results of the TRIDENT-2 study20221130163901

Clinical impact of additional findings detected by genome-wide non-invasive prenatal testing: Follow-up results of the TRIDENT-2 study

[published correction appears in Am J Hum Genet. 2022 Jul 7;109(7):1344]. van Prooyen Schuurman L, Sistermans EA, Van Opstal D, et al. Am J Hum Genet. 2022;109(6):1140-1152. doi:10.1016/j.ajhg.2022.04.018. Open Access: Learn more

Tags: Clinical Experience / Clinical Utility, 2022, Netherlands, RAAs, CNVs

  • “Between April 2017 and April 2019, additional findings were detected in 402/110,739 pregnancies (0.36%). For 358 cases, the origin was proven to be either fetal (n = 79; 22.1%), (assumed) confined placental mosaicism (CPM) (n = 189; 52.8%), or maternal (n = 90; 25.1%). For the remaining 44 (10.9%), the origin of the aberration could not be determined. Most fetal chromosomal aberrations were pathogenic and associated with severe clinical phenotypes (61/79; 77.2%). For CPM cases, occurrence of pre-eclampsia (8.5% [16/189] vs 0.5% [754/159,924]; RR 18.5), and birth weight <2.3rd percentile (13.6% [24/177] vs 2.5% [3,892/155,491]; RR 5.5) were significantly increased compared to the general obstetric population. Of the 90 maternal findings, 12 (13.3%) were malignancies and 32 (35.6%) (mosaic) pathogenic copy number variants, mostly associated with mild or no clinical phenotypes.”
  • “In conclusion, about one in every 275 women in a general obstetric population opting for GW-NIPT receives an additional finding. The majority of additional findings identified by GW-NIPT have clinical impact. Most fetal chromosomal aberrations are pathogenic and associated with severe clinical phenotypes. (Assumed) CPM is significantly associated with adverse perinatal outcomes, requiring tailored obstetric care.”
Clinical evaluation of non-invasive prenatal screening for the detection of fetal genome-wide copy number variants.20221130163718

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.
Whole genome non-invasive prenatal testing in prenatal screening algorithm: clinical experience from 12,700 pregnancies.20221130163326

Whole genome non-invasive prenatal testing in prenatal screening algorithm: clinical experience from 12,700 pregnancies.

Baranova EE, Sagaydak OV, Galaktionova AM, et al. BMC Pregnancy Childbirth. 2022;22(1):633. Published 2022 Aug 9. doi:10.1186/s12884-022-04966-8. Open Access: Learn more

Tags: Clinical Experience / Clinical Utility, 2022, Russia, RAAs, CNVs

  • “258 (2.0%) samples with positive NIPT results were detected including 126 cases of trisomy 21 (T21), 40 cases of T18, 12 cases of T13, 41 cases of sex chromosome aneuploidies (SCAs) and 39 cases of rare autosomal aneuploidies (RAAs) and significant copy number variations (CNVs).”
  • The most common RAAs were T7 (n=6), T16 (n=4), T8 (n=3) and T22 (n=3).

PPVs were 98.26% for T12, 91.67% for T18/13, 57.14% for SCAs, and 44.83% for RAAs/CNVs.

Multisite assessment of the impact of cell-free DNA-based screening for rare autosomal aneuploidies on pregnancy management and outcomes.20221130163126

Multisite assessment of the impact of cell-free DNA-based screening for rare autosomal aneuploidies on pregnancy management and outcomes.

Mossfield T, Soster E, Menezes M, et al. Front Genet. 2022;13:975987. Published 2022 Aug 29. doi:10.3389/fgene.2022.975987. Open Access: Learn more

Tags: Clinical Experience / Clinical Utility, 2022, International, RAAs, Consortium Publication

  • “Here, we describe a multi-cohort, global retrospective study that looked at the clinical outcomes of cases with a high-risk cfDNA screening result for a RAA. Our study cohort included a total of 109 cases from five different sites, with diagnostic outcome information available for 68% (74/109) of patients. Based on confirmatory diagnostic testing, we found a concordance rate of 20.3% for presence of a RAA (15/74) in our study population. Pregnancy outcome was also available for 77% (84/109) of cases in our cohort. Many of the patients experienced adverse pregnancy outcomes, including intrauterine fetal demise, fetal growth restriction, and preterm birth. These adverse outcomes were observed both in patients with fetal or placental confirmation of the presence of a RAA, as well as patients that did not undergo fetal and/or placental diagnostic testing.”
  • “In addition, we have proposed some suggestions for pregnancy management and counseling considerations for situations where a RAA is noted on a cfDNA screen.”
  • “In conclusion, our study has shown that genome-wide cfDNA screening for the presence of rare autosomal aneuploidies can be beneficial for both patients and their healthcare practitioners. This can provide a possible explanation for an adverse pregnancy outcome or result in a change in pregnancy management, such as increased monitoring for adverse outcomes.”
Cell-free DNA screening for rare autosomal trisomies and segmental chromosome imbalances.20221130163005

Cell-free DNA screening for rare autosomal trisomies and segmental chromosome imbalances.

Raymond YC, Fernando S, Menezes M, et al. Prenat Diagn. 2022;42(11):1349-1357. doi:10.1002/pd.6233. Open Access: Learn more

Tags: Clinical Experience / Clinical Utility, 2022, Australia, RAAs, CNVs

  • “Among 23,857 women screened, there were 93 high-risk results for RATs (0.39%) and 82 for SIs [structural imbalances] (0.34%). The PPVs were 3.8% (3/78, 95% CI 0.8%-10.8%) for RATs and 19.1% (13/68, 95% CI 10.6%-30.5%) for SIs. If fetuses with structural anomalies were also counted as true-positive cases, the PPV for RATS increased to 8.5% (7/82, 95% CI 3.5%-16.8%). Among 85 discordant cases with birth outcomes available (65.4%), discordant positive RATs had a significantly higher proportion of infants born below the 10th and 3rd birthweight percentiles than expected (19.6% (p = 0.022) and 9.8% (p = 0.004), respectively), which was not observed in the SI group (2.9% < 10th (p = 0.168) and 0.0% <3rd (p = 0.305)).”
A retrospective single-center analysis of prenatal diagnosis and follow-up of 626 chinese patients with positive non-invasive prenatal screening results.20221130162822

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.”
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