Journal of Genetic Medicine

  • 제14권1호
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  • Pages.1-7
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  • 2017
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  • 1226-1769(pISSN)
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  • 2383-8442(eISSN)
대한의학유전학회 (Korean Society of Medical Genetics and Genomics)
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First trimester screening for trisomy 18 by a combination of nuchal translucency thickness and epigenetic marker level

  • Lee, Da Eun (Laboratory of Medical Genetics, Medical Research Institute, Cheil General Hospital and Women's Healthcare Center) ;
  • Kim, Shin Young (Laboratory of Medical Genetics, Medical Research Institute, Cheil General Hospital and Women's Healthcare Center) ;
  • Kim, Hyun Jin (Laboratory of Medical Genetics, Medical Research Institute, Cheil General Hospital and Women's Healthcare Center) ;
  • Park, So Yeon (Laboratory of Medical Genetics, Medical Research Institute, Cheil General Hospital and Women's Healthcare Center) ;
  • Kim, Min Hyoung (Department of Obstetrics and Gynecology, Cheil General Hospital and Women's Healthcare Center, Dankook University College of Medicine) ;
  • Han, You Jung (Department of Obstetrics and Gynecology, Cheil General Hospital and Women's Healthcare Center, Dankook University College of Medicine) ;
  • Ryu, Hyun Mee (Laboratory of Medical Genetics, Medical Research Institute, Cheil General Hospital and Women's Healthcare Center)
  • 투고 : 2017.05.08
  • 심사 : 2017.06.14
  • 발행 : 2017.06.30
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초록

Purpose: The aim of this study was to assess the diagnostic efficacy of noninvasive prenatal screening for trisomy 18 by assessing the levels of unmethylated-maspin (U-maspin) and fetal nuchal translucency (NT) thickness during the first trimester of pregnancy. Materials and Methods: A nested case-control study was conducted using maternal plasma samples collected from 65 pregnant women carrying 11 fetuses with trisomy 18 and 54 normal fetuses. We compared the U-maspin levels, NT thicknesses, or a combination of both in the first trimester between the case and control groups. Results: U-maspin levels and NT thickness were significantly elevated in the first trimester in pregnant women carrying fetuses with trisomy 18 when compared to those carrying normal fetuses (27.2 vs. 6.6 copies/mL, P<0.001 for U-maspin; 5.9 vs. 2.0 mm, P<0.001 for NT). The sensitivities of the U-maspin levels and NT thickness in prenatal screening for fetal trisomy 18 were 90.9% and 90.9%, respectively, with a specificity of 98.1%. The combined U-maspin levels and NT thickness had a sensitivity of 100% in prenatal screening for fetal trisomy 18, with a specificity of 98.1%. Conclusion: A combination of U-maspin levels and NT thickness is highly efficacious for noninvasive prenatal screening of fetal trisomy 18 in the first trimester of pregnancy.

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참고문헌

  1. Snijders RJ, Sebire NJ, Nicolaides KH. Maternal age and gestational age-specific risk for chromosomal defects. Fetal Diagn Ther 1995;10:356-67. https://doi.org/10.1159/000264259
  2. Bestwick JP, Huttly WJ, Wald NJ. Detection of trisomy 18 and trisomy 13 using first and second trimester Down's syndrome screening markers. J Med Screen 2013;20:57-65. https://doi.org/10.1177/0969141313484904
  3. Snijders RJ, Noble P, Sebire N, Souka A, Nicolaides KH. UK multicentre project on assessment of risk of trisomy 21 by maternal age and fetal nuchal-translucency thickness at 10-14 weeks of gestation. Fetal Medicine Foundation First Trimester Screening Group. Lancet 1998;352:343-6. https://doi.org/10.1016/S0140-6736(97)11280-6
  4. Makrydimas G, Sotiriadis A, Ioannidis JP. Screening performance of first-trimester nuchal translucency for major cardiac defects: a metaanalysis. Am J Obstet Gynecol 2003;189:1330-5. https://doi.org/10.1067/S0002-9378(03)00645-8
  5. von Kaisenberg CS, Krenn V, Ludwig M, Nicolaides KH, Brand-Saberi B. Morphological classification of nuchal skin in human fetuses with trisomy 21, 18, and 13 at 12-18 weeks and in a trisomy 16 mouse. Anat Embryol (Berl) 1998;197:105-24. https://doi.org/10.1007/s004290050123
  6. Souka AP, Krampl E, Geerts L, Nicolaides KH. Congenital lymphedema presenting with increased nuchal translucency at 13 weeks of gestation. Prenat Diagn 2002;22:91-2. https://doi.org/10.1002/pd.104
  7. Tercanli S, Miny P, Siebert MS, Hosli I, Surbek DV, Holzgreve W. Fanconi anemia associated with increased nuchal translucency detected by first-trimester ultrasound. Ultrasound Obstet Gynecol 2001;17:160-2. https://doi.org/10.1046/j.1469-0705.2001.00321.x
  8. Miron P, Cote YP, Lambert J. Nuchal translucency thresholds in prenatal screening for Down syndrome and trisomy 18. J Obstet Gynaecol Can 2009;31:227-35. https://doi.org/10.1016/S1701-2163(16)34121-4
  9. Sepulveda W, Wong AE, Dezerega V. First-trimester sonographic findings in trisomy 18: a review of 53 cases. Prenat Diagn 2010;30:256-9.
  10. Nicolaides KH. Nuchal translucency and other first-trimester sonographic markers of chromosomal abnormalities. Am J Obstet Gynecol 2004;191:45-67. https://doi.org/10.1016/j.ajog.2004.03.090
  11. Tong YK, Jin S, Chiu RW, Ding C, Chan KC, Leung TY, et al. Noninvasive prenatal detection of trisomy 21 by an epigenetic-genetic chromosome-dosage approach. Clin Chem 2010;56:90-8. https://doi.org/10.1373/clinchem.2009.134114
  12. Tsui DW, Lam YM, Lee WS, Leung TY, Lau TK, Lau ET, et al. Systematic identification of placental epigenetic signatures for the noninvasive prenatal detection of Edwards syndrome. PLoS One 2010;5:e15069. https://doi.org/10.1371/journal.pone.0015069
  13. Lim JH, Kim SY, Park SY, Lee SY, Kim MJ, Han YJ, et al. Non-invasive epigenetic detection of fetal trisomy 21 in first trimester maternal plasma. PLoS One 2011;6:e27709. https://doi.org/10.1371/journal.pone.0027709
  14. Dokras A, Gardner LM, Kirschmann DA, Seftor EA, Hendrix MJ. The tumour suppressor gene maspin is differentially regulated in cytotrophoblasts during human placental development. Placenta 2002;23:274-80. https://doi.org/10.1053/plac.2001.0784
  15. Tong YK, Ding C, Chiu RW, Gerovassili A, Chim SS, Leung TY, et al. Noninvasive prenatal detection of fetal trisomy 18 by epigenetic allelic ratio analysis in maternal plasma: theoretical and empirical considerations. Clin Chem 2006;52:2194-202. https://doi.org/10.1373/clinchem.2006.076851
  16. Lo YM, Tein MS, Lau TK, Haines CJ, Leung TN, Poon PM, et al. Quantitative analysis of fetal DNA in maternal plasma and serum: implications for noninvasive prenatal diagnosis. Am J Hum Genet 1998;62:768-75. https://doi.org/10.1086/301800
  17. The Fetal Medicine Foundation. 11-13 week scan. Nuchal translucency. Protocol for measurement of nuchal translucency. [https://fetalmedicine.org/training-n-certification/certificates-of-competence/nuchal-translucency-scan]
  18. Souka AP, Snijders RJ, Novakov A, Soares W, Nicolaides KH. Defects and syndromes in chromosomally normal fetuses with increased nuchal translucency thickness at 10-14 weeks of gestation. Ultrasound Obstet Gynecol 1998;11:391-400. https://doi.org/10.1046/j.1469-0705.1998.11060391.x
  19. Souka AP, Krampl E, Bakalis S, Heath V, Nicolaides KH. Outcome of pregnancy in chromosomally normal fetuses with increased nuchal translucency in the first trimester. Ultrasound Obstet Gynecol 2001;18:9-17. https://doi.org/10.1046/j.1469-0705.2001.00454.x
  20. Sherod C, Sebire NJ, Soares W, Snijders RJ, Nicolaides KH. Prenatal diagnosis of trisomy 18 at the 10-14-week ultrasound scan. Ultrasound Obstet Gynecol 1997;10:387-90. https://doi.org/10.1046/j.1469-0705.1997.10060387.x
  21. Tul N, Spencer K, Noble P, Chan C, Nicolaides K. Screening for trisomy 18 by fetal nuchal translucency and maternal serum free beta-hCG and PAPP-A at 10-14 weeks of gestation. Prenat Diagn 1999;19:1035-42. https://doi.org/10.1002/(SICI)1097-0223(199911)19:11<1035::AID-PD694>3.0.CO;2-2
  22. Chim SS, Tong YK, Chiu RW, Lau TK, Leung TN, Chan LY, et al. Detection of the placental epigenetic signature of the maspin gene in maternal plasma. Proc Natl Acad Sci U S A 2005;102:14753-8. https://doi.org/10.1073/pnas.0503335102
  23. Wapner R, Thom E, Simpson JL, Pergament E, Silver R, Filkins K, et al. First-trimester screening for trisomies 21 and 18. N Engl J Med 2003;349:1405-13. https://doi.org/10.1056/NEJMoa025273
  24. Wright D, Kagan KO, Molina FS, Gazzoni A, Nicolaides KH. A mixture model of nuchal translucency thickness in screening for chromosomal defects. Ultrasound Obstet Gynecol 2008;31:376-83. https://doi.org/10.1002/uog.5299
  25. Kagan KO, Wright D, Valencia C, Maiz N, Nicolaides KH. 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 2008;23:1968-75. https://doi.org/10.1093/humrep/den224