Does isolated nuchal translucency from 2.5 to 2.9 mm increase the risk of fetal chromosome disease?

Yin, Daishu; Chen, Lin; Wang, Li; Zeng, Yang; Tang, Feng; Wang, Jing

doi:10.1007/s00438-022-01948-5

Cited by 3 publications

(4 citation statements)

References 33 publications

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“…The detection rates of aneuploidy and CNVs in fetuses with NT 95th percentile-2.99 mm were high, while the incremental yield of monogenic disorders was 0%. Therefore, we suggest, as most of the literature (Wang et al, 2022;Xie et al, 2022;Yin et al, 2022) To assess the risk of chromosomal abnormalities in fetuses with NT of 3.0-3.49 mm and to determine whether invasive prenatal testing is necessary, our results showed an 11.7% risk of chromosomal abnormalities (including aneuploidy and pCNVs). The study by Petersen et al (2020) performed a meta-analysis of literature cases with NT of 3.0-3.49 mm and a retrospective study of two groups of pregnant women with invasive testing and CMA, which showed 13.5% of 522 fetuses were diagnosed with chromosomal aberrations, similar to the results of our study.…”

Section: Discussionmentioning

confidence: 79%

“…The detection rates of aneuploidy and CNVs in fetuses with NT 95th percentile-2.99 mm were high, while the incremental yield of monogenic disorders was 0%. Therefore, we suggest, as most of the literature ( Wang et al, 2022 ; Xie et al, 2022 ; Yin et al, 2022 ) recommends that instead of invasive prenatal diagnosis for those fetuses, NIPT-Plus, which not only has high sensitivity and specificity for aneuploidy and CNVs, but also has already in large-scale clinical use in China and abroad, may be performed first especially if other structural abnormalities have not been added at the time of NT measurement. If the non-invasive results are negative, the invasive prenatal diagnosis can be left alone and follow-up ultrasound monitoring, including systemic ultrasound test and cardiac ultrasound test, can be performed to assess pregnancy outcome.…”

Section: Discussionmentioning

confidence: 99%

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When NIPT meets WES, prenatal diagnosticians face the dilemma: genetic etiological analysis of 2,328 cases of NT thickening and follow-up of pregnancy outcomes

et al. 2023

Front. Genet.

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Objective: To assess the performance of diverse prenatal diagnostic approaches for nuchal translucency (NT) thickening and to investigate the optimal prenatal screening or diagnostic action with a NT thickening of 95th percentile-3.50 mm.Methods: A retrospective analysis of 2,328 pregnancies with NT ≥ 95th percentile through ultrasound-guided transabdominal chorionic villus sampling (CVS), amniocentesis, or cordocentesis obtained clinical samples (chorionic villi, amniotic fluid, and cord blood), and real-time quantitative fluorescent PCR (QF-PCR), chromosome karyotyping (CS), chromosome microarray analysis (CMA), or whole exome sequencing (WES) were provided to identify genetic etiologies.Results: In this study, the incidence of chromosomal defects increased with NT thickness. When NT ≥ 6.5 mm, 71.43% were attributed to genetic abnormalities. The 994 gravidas with fetal NT thickening underwent short tandem repeat (STR), CS, and CMA. In 804 fetuses with normal karyotypes, CMA detected 16 (1.99%) extra pathogenic or likely pathogenic copy number variations (CNVs). The incremental yield of CMA was only 1.16% (3/229) and 3.37% (10/297) in the group with NT 95th percentile-2.99 mm and NT 3.0–3.49 mm, separately. Among the 525 gravidas with fetal NT thickening who underwent STR, CMA, and WES, the incremental yield of WES was 4.09% (21/513). In the group of NT 95th percentile-2.99 mm, there were no additional single-nucleotide variations (SNVs) detected in WES, while in 143 cases with NT of 3.0–3.49 mm, the incremental yield of WES was 5.59% (8/143).Conclusion: In the group of NT 95th percentile-3.0 mm, since chromosomal aneuploidy and chromosomal copy number variation were the primary causes and the additional contribution of CMA and WES was not significant, we recommend NIPT-Plus for pregnant women with a NT thickening of 95th percentile-3.0 mm first. In addition, comprehensive prenatal genetic testing involving CMA and WES can benefit pregnancies with NT thickening of 3.0–3.49 mm.

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Section: Discussionmentioning

confidence: 79%

“…The detection rates of aneuploidy and CNVs in fetuses with NT 95th percentile-2.99 mm were high, while the incremental yield of monogenic disorders was 0%. Therefore, we suggest, as most of the literature ( Wang et al, 2022 ; Xie et al, 2022 ; Yin et al, 2022 ) recommends that instead of invasive prenatal diagnosis for those fetuses, NIPT-Plus, which not only has high sensitivity and specificity for aneuploidy and CNVs, but also has already in large-scale clinical use in China and abroad, may be performed first especially if other structural abnormalities have not been added at the time of NT measurement. If the non-invasive results are negative, the invasive prenatal diagnosis can be left alone and follow-up ultrasound monitoring, including systemic ultrasound test and cardiac ultrasound test, can be performed to assess pregnancy outcome.…”

Section: Discussionmentioning

confidence: 99%

When NIPT meets WES, prenatal diagnosticians face the dilemma: genetic etiological analysis of 2,328 cases of NT thickening and follow-up of pregnancy outcomes

et al. 2023

Front. Genet.

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“…Similarly, a tertiary care center in China observed a rate of 6.2% in fetuses with NT ranging from the 95th percentile to 3.0 mm (7). However, other studies documented lower rates, such as 5.1% reported by Yin et al (9), while Wang et al noted a higher rate of 12.7% (8). A recent systematic meta-analysis by Mastromoro et al, reported a range of 8.4 to 13.0% for the chromosomal abnormality detection rate in the NT 2.5-2.9 mm group, compared to 6.6% ~ 33.8% for the NT 3.0-3.4 mm group (12).…”

Section: Discussionmentioning

confidence: 88%

“…There is increasing evidence suggesting a potential increase in the risk of fetal abnormalities when fetal nuchal translucency thickness falls within the range of 2.5 mm to 2.9 mm (7)(8)(9). However, the limited number of cases within this NT range and the widely varying risk values pose challenges.…”

Section: Introductionmentioning

confidence: 99%

Associations between genomic aberrations, increased nuchal translucency, and pregnancy outcomes: a comprehensive analysis of 2,272 singleton pregnancies in women under 35

Huang,

Wu,

et al. 2024

Front. Med.

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ObjectivesRegarding increased nuchal translucency (NT), the cutoff values used are heterogeneous in clinical practice, this study aims to assess the efficacy of prenatal detection for chromosomal abnormalities and pregnancy outcomes in fetuses with varying NT thicknesses, in order to provide data that supports informed prenatal diagnosis and genetic counseling for such cases.MethodsWe included 2,272 pregnant women under 35 with singleton pregnancies who underwent invasive prenatal diagnosis between 2014 and 2022. The cohort comprised 2,010 fetuses with increased NT (≥2.5 mm) and 262 fetuses with normal NT but exhibiting a single soft marker. Prenatal diagnoses were supported by chromosomal microarray (CMA) and copy number variation sequencing (CNV-seq) analyses.ResultsThe detection rates of numerical chromosomal abnormalities were 15.4% (309/2,010) and 17.3% (297/1,717) in the NT ≥2.5 and ≥ 3.0 groups, respectively. Pathogenic/likely pathogenic CNV incidence increased with NT thickness (χ2 = 8.60, p < 0.05), peaking at 8.7% (22/254) in the NT 4.5–5.4 mm group. Structural defects were found in 18.4% of fetuses with NT values between 2.5 mm and 2.9 mm. Chromosomal abnormality rates in the isolated increased NT groups of 2.5–2.9 mm and 3.0–3.4 mm were 6.7% (16/239) and 10.0% (47/470), respectively, with no statistical significance (χ2 = 2.14, p > 0.05). Fetuses with NT thickness between 2.5 and 2.9 mm combined with the presence of soft markers or non-lethal structural abnormalities exhibited a significantly higher chromosomal abnormality risk (19.0%) compared to fetuses with isolated increased NT ranging from 3.5 to 4.4 mm (13.0%). Pregnancy termination rates increased with NT thickness (χ2 = 435.18, p < 0.0001), ranging from 12.0% (30/249) in the NT 2.5–2.9 mm group to 87.0% (141/162) in the NT ≥ 6.5 mm group.ConclusionCMA or CNV-seq exhibited good performance in identifying genomic aberrations in pregnancies with increased NT thickness. NT ranging from 2.5 mm to 2.9 mm elevated the risk of fetal chromosomal abnormalities, particularly when combined with other soft markers.

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The Role of Thickened Nuchal Translucency on Copy Number Variations and Pregnancy Outcomes in Northeast Coast of Fujian Province, China: A Comparison Between Traditional Karyotyping and Single Nucleotide Polymorphism Array Analysis

Cao,

Huang,

Dong

et al. 2023

Preprint

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Background Thickened nuchal translucency (NT; ≥2.5 mm) is closely associated with various chromosomal abnormalities, structural abnormalities, and genetic diseases. However, the cutoff value of thickened NT for invasive prenatal diagnosis remains inconsistent, and little research has been conducted on pathogenic copy number variations (CNVs) affecting the outcomes in foetuses with thickened NT. This study aimed to assess the cutoff value for thickened NT to predict aneuploid foetuses and CNVs associated with thickened NT in prenatal diagnosis to determine the characteristics of pathogenic CNVs, which would assist the genetic counselling of women with thickened NT. Methods Ninety pregnant women with thickened NT who underwent invasive prenatal diagnosis using traditional karyotyping and single nucleotide polymorphism (SNP) array analysis in diagnostic institutions between January 2021 and March 2023 were included. The accuracy of the thickened NT cutoff value for diagnosing aneuploid abnormalities was assessed using receiver operating characteristic (ROC) curve analysis. Results Karyotype analysis identified 15 chromosomal abnormalities. In addition to the 10 chromosomal abnormalities corresponding to routine karyotyping, SNP array analysis identified six patients with CNVs but normal karyotypes. ROC curves demonstrate that the NT measured between 11 and 13+ 6 weeks was associated with 0.729 area under the curve (AUC; 95% CI: 0.56–0.898, P = 0.019) with the foetal aneuploidy. The ROC curve revealed that the cutoff value of NT was 4.15 mm, which showed 50% sensitivity and 90% specificity for detecting aneuploidies. With increasing NT thickness, the probability of aneuploidy increases in the first trimester. Conclusion Aneuploid abnormalities and CNVs are closely related to a thickened NT, which affects pregnancy outcomes. Thickened NT and abnormal CNVs are closely related and are not only associated with chromosome aneuploidy in the first trimester. We recommend that karyotyping and SNP array analysis should be performed for prenatal diagnosis in all foetus with NT thickness > 2.5 mm, regardless of NT thickness > 3.0 or 3.5 mm to avoid the occurrence of child birth with genetic defects due to missing prenatal diagnosis.

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Does isolated nuchal translucency from 2.5 to 2.9 mm increase the risk of fetal chromosome disease?

Cited by 3 publications

References 33 publications

When NIPT meets WES, prenatal diagnosticians face the dilemma: genetic etiological analysis of 2,328 cases of NT thickening and follow-up of pregnancy outcomes

When NIPT meets WES, prenatal diagnosticians face the dilemma: genetic etiological analysis of 2,328 cases of NT thickening and follow-up of pregnancy outcomes

Associations between genomic aberrations, increased nuchal translucency, and pregnancy outcomes: a comprehensive analysis of 2,272 singleton pregnancies in women under 35

The Role of Thickened Nuchal Translucency on Copy Number Variations and Pregnancy Outcomes in Northeast Coast of Fujian Province, China: A Comparison Between Traditional Karyotyping and Single Nucleotide Polymorphism Array Analysis

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