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Diagnostic yield of copy number variation sequencing in fetuses with increased nuchal translucency: a retrospective study

  • Maternal-fetal Medicine
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Objective

To assess the efficacy of copy number variation sequencing (CNV-seq) and karyotyping for prenatal detection of chromosomal abnormalities in fetuses with increased nuchal translucency.

Methods

Amniotic fluid samples were extracted from 205 fetuses with increased nuchal translucency (NT ≥ 2.5 mm), diagnosed by ultrasound between gestational ages of 11 and 13 + 6 weeks. Karyotyping and CNV-seq were performed for detecting chromosomal abnormalities.

Results

There are 40 fetuses (19.51%) showing increased NT detected with chromosomal abnormalities in karyotyping, and trisomy 21 was found to be the most common abnormalities. There are 50 fetuses (24.39%) identified with chromosomal abnormalities by CNV-seq. The detection of the applied techniques indicated that CNV-seq revealed higher chromosomal aberrations. The risk of chromosomal abnormalities was significantly increased with NT thickening, from 13.64% in the NT group of 2.5–3.4 mm, 38.64% in the NT group of 3.5–4.4 mm, and to 51.72% in the NT group of over 4.5 mm (P < 0.05). The investigated cases with increased NT with presence of soft markers in ultrasound or high risk in non-invasive prenatal testing presented chromosomal abnormalities in higher rates, comparing with those with isolated NT or low risk (P < 0.05).

Conclusion

The results indicated that the risk of chromosomal abnormalities was associated with the NT thickness, detected by karyotype or CNV-seq. The combination application of two analysis was efficient to reveal the possible genetic defects in prenatal diagnosis. The finding suggested that the detection should be considered with ultrasonographic soft markers, and the NT thickness of 2.5–3.4 mm could be a critical value for detecting chromosomal abnormalities to prevent the occurrence of missed diagnosis.

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Data availability

The row data for this study are available on request to the corresponding author.

References

  1. Grande M, Jansen FA, Blumenfeld YJ, Fisher A, Odibo AO, Haak MC et al (2015) Genomic microarray in fetuses with increased nuchal translucency and normal karyotype: a systematic review and meta-analysis. Ultrasound Obstet Gynecol 46(6):650–658

    Article  CAS  PubMed  Google Scholar 

  2. Matyasova M, Dobsakova Z, Hiemerova M, Kadlecova J, Nikulenkov Grochova D, Popelinska E et al (2019) Prenatal diagnosis of Noonan syndrome in fetuses with increased nuchal translucency and a normal karyotype. Ceska Gynekol 84(3):195–200

    CAS  PubMed  Google Scholar 

  3. Lan L, Wu H, She L, Zhang B, He Y, Luo D et al (2020) Analysis of copy number variation by sequencing in fetuses with nuchal translucency thickening. J Clin Lab Anal 34(8):e23347

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Souka AP, Krampl E, Bakalis S, Heath V, Nicolaides KH (2001) Outcome of pregnancy in chromosomally normal fetuses with increased nuchal translucency in the first trimester. Ultrasound Obstet Gynecol 18(1):9–17

    Article  CAS  PubMed  Google Scholar 

  5. Pergament E, Alamillo C, Sak K, Fiddler M (2011) Genetic assessment following increased nuchal translucency and normal karyotype. Prenat Diagn 31(3):307–310

    Article  PubMed  Google Scholar 

  6. Baer RJ, Norton ME, Shaw GM, Flessel MC, Goldman S, Currier RJ et al (2014) Risk of selected structural abnormalities in infants after increased nuchal translucency measurement. Am J Obstet Gynecol 211(6):675

    Article  Google Scholar 

  7. Scholl J, Durfee SM, Russell MA, Heard AJ, Iyer C, Alammari R et al (2012) First-trimester cystic hygroma: relationship of nuchal translucency thickness and outcomes. Obstet Gynecol 120(3):551–559

    Article  PubMed  Google Scholar 

  8. Bilardo CM, Muller MA, Pajkrt E, Clur SA, van Zalen MM, Bijlsma EK (2007) Increased nuchal translucency thickness and normal karyotype: time for parental reassurance. Ultrasound Obstet Gynecol 30(1):11–18

    Article  CAS  PubMed  Google Scholar 

  9. Screening for Fetal Chromosomal Abnormalities (2020) ACOG practice bulletin, number 226. Obstet Gynecol 136(4):e48–e69

    Article  Google Scholar 

  10. Kim MH, Park SH, Cho HJ, Choi JS, Kim JO, Ahn HK et al (2006) Threshold of nuchal translucency for the detection of chromosomal aberration: comparison of different cut-offs. J Korean Med Sci 21(1):11–14

    Article  PubMed  PubMed Central  Google Scholar 

  11. Su L, Huang H, An G, Cai M, Wu X, Li Y et al (2019) Clinical application of chromosomal microarray analysis in fetuses with increased nuchal translucency and normal karyotype. Mol Genet Genomic Med 7(8):e811

    Article  PubMed  PubMed Central  Google Scholar 

  12. Zhang Z, Hu T, Wang J, Li Q, Wang H, Liu S (2019) Prenatal diagnostic value of chromosomal microarray in fetuses with nuchal translucency greater than 2.5 mm. Biomed Res Int 2019:6504159

    Article  PubMed  PubMed Central  Google Scholar 

  13. Zhang R, Chen X, Wang D, Chen X, Wang C, Zhang Y et al (2019) Prevalence of chromosomal abnormalities identified by copy number variation sequencing in high-risk pregnancies, spontaneous abortions, and suspected genetic disorders. J Int Med Res 47(3):1169–1178

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Zhu X, Li J, Ru T, Wang Y, Xu Y, Yang Y et al (2016) Identification of copy number variations associated with congenital heart disease by chromosomal microarray analysis and next-generation sequencing. Prenat Diagn 36(4):321–327

    Article  CAS  PubMed  Google Scholar 

  15. Riggs ER, Andersen EF, Cherry AM, Kantarci S, Kearney H, Patel A et al (2020) Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med 22(2):245–257

    Article  PubMed  Google Scholar 

  16. Nicolaides KH (2004) Nuchal translucency and other first-trimester sonographic markers of chromosomal abnormalities. Am J Obstet Gynecol 191(1):45–67

    Article  PubMed  Google Scholar 

  17. Kagan KO, Avgidou K, Molina FS, Gajewska K, Nicolaides KH (2006) Relation between increased fetal nuchal translucency thickness and chromosomal defects. Obstet Gynecol 107(1):6–10

    Article  PubMed  Google Scholar 

  18. Kagan KO, Wright D, Valencia C, Maiz N, Nicolaides KH (2008) Screening for trisomies 21, 18 and 13 by maternal age, fetal nuchal translucency, fetal heart rate, free beta-hCG and pregnancy-associated plasma protein-A. Hum Reprod 23(9):1968–1975

    Article  CAS  PubMed  Google Scholar 

  19. Jin H, Wang J, Zhang G, Jiao H, Zhu J, Li Z et al (2021) A Chinese multicenter retrospective study of isolated increased nuchal translucency associated chromosome anomaly and prenatal diagnostic suggestions. Sci Rep 11(1):5596

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Zhao XR, Gao L, Wu Y, Wang YL (2020) Application of chromosomal microarray in fetuses with increased nuchal translucency. J Matern Fetal Neonatal Med 33(10):1749–1754

    Article  PubMed  Google Scholar 

  21. Song Y, Liu C, Qi H, Zhang Y, Bian X, Liu J (2013) Noninvasive prenatal testing of fetal aneuploidies by massively parallel sequencing in a prospective Chinese population. Prenat Diagn 33(7):700–706

    Article  PubMed  Google Scholar 

  22. Wang W, Lu F, Zhang B, Zhou Q, Chen Y, Yu B (2022) Clinical evaluation of non-invasive prenatal screening for the detection of fetal genome-wide copy number variants. Orphanet J Rare Dis 17(1):253

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We are grateful to Berry Genomics for technical assistance and to all participants.

Funding

The financial grant was supported by State Key Development Program of Basic Research of China (973 Program) (grant no. 2018YFC1002904).

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China

    Xiao Yang, Xinyi Bian, Xinwei Shi, Jianlin Ding, Hongju Tang, Peng Xu, Dongrui Deng, Wanjiang Zeng, Suhua Chen, Fuyuan Qiao, Ling Feng & Yuanyuan Wu

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  1. Xiao Yang
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  2. Xinyi Bian
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  3. Xinwei Shi
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  4. Jianlin Ding
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  5. Hongju Tang
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  6. Peng Xu
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  7. Dongrui Deng
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  8. Wanjiang Zeng
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  9. Suhua Chen
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  10. Fuyuan Qiao
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  11. Ling Feng
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  12. Yuanyuan Wu
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Contributions

WYY, BXY and YX were involved in the conception and design. DJL, THJ, XP contributed to the acquisition and analysis of data. SXW, BXY and YX wrote the paper. All the authors participated in the revision of the manuscript, read and approved the final version of the manuscript.

Corresponding author

Correspondence to Yuanyuan Wu.

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Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Ethical approval and consent to participate

This study was approved by the Peking University Third Hospital Medical Science Research Ethics Committee (ethics approval number: M2019036). This project is a joint study completed cooperatively by Tongji Hospital and Peking University Third Hospital (the main undertaking unit, responsible for completing the ethical approval of medical research). All participants in this study were fully informed of the purpose of the study and had signed the informed consent. All the experiment protocols in this manuscript were carried out in accordance to the Declaration of Helsinki.

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Informed consent was obtained from all individual participants included in the study.

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Yang, X., Bian, X., Shi, X. et al. Diagnostic yield of copy number variation sequencing in fetuses with increased nuchal translucency: a retrospective study. Arch Gynecol Obstet 309, 139–144 (2024). https://doi.org/10.1007/s00404-022-06900-x

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  • DOI: https://doi.org/10.1007/s00404-022-06900-x

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