Archives of Gynecology and Obstetrics

, Volume 281, Issue 3, pp 393–399 | Cite as

Analysis of the distribution shift of detected aneuploidies by age independent first trimester screening

  • Peter Schmidt
  • C. Hörmansdörfer
  • M. Golatta
  • A. Scharf
Original Article

Abstract

Introduction

First trimester screening (FTS) became standard in non-invasive testing for chromosomal abnormalities in early pregnancy. The individual risk is calculated on the basis of a general background risk, which refers to the maternal age. A new method, Advanced Firsttrimester Screening (AFS) excludes the background risk in its algorithm. This study had the aim to analyze how the detection of aneuploidies is influenced by the in- or exclusion of the maternal age in the risk calculation.

Materials and methods

The data of 15,228 first trimester screenings were recalculated with FTS and AFS. The study cohort was divided by age into nine groups and the numbers of detected cases were recorded according to the groups of age.

Results

Of 129 detected aneuploidies 90% got the same test results, disregarding whether risk assessment is performed including maternal age or not. FTS detected five aneuploidies at age 35 or older that were not recorded by AFS. AFS detected six aneuploidies that were not detected by FTS. Out of these, the oldest mother was 32 years old.

Discussion

When excluding the maternal age from risk calculation, the detection of aneuploidies showed a shift from older to younger women. Overall, the detection rate did not change significantly. However, the false positive rate was 25% lower with the exclusion of maternal age.

Keywords

First trimester screening Nuchal translucency Aneuploidy Risk assessment Maternal age 

References

  1. 1.
    Krampl E, Wertaschnigg D, Husslein P (2002) Down-syndrom-screening im ersten Trimenon. Geburtshilfe Frauenheilkd 62(9):843–848. doi:10.1055/s-2002-33894 CrossRefGoogle Scholar
  2. 2.
    Wapner R, Thom E, Simpson JL, Pergament E, Silver R, Filkins K, Platt L, Mahoney M, Johnson A, Hogge WA, Wilson RD, Mohide P, Hershey D, Krantz D, Zachary J, Snijders R, Greene N, Sabbagha R, MacGregor S, Hill L, Gagnon A, Hallahan T, Jackson L (2003) First-trimester screening for trisomy-21 and 18. N Engl J Med 349:1405–1413. doi:10.1056/NEJMoa025273 CrossRefPubMedGoogle Scholar
  3. 3.
    Snijders RJM, Sundberg K, Holzgreve W, Henry G, Nicolaides KH (1999) Maternal age and gestation-specific risk for trisomy 21. Ultrasound Obstet Gynecol 14:167–170. doi:10.1046/j.1469-0705.1999.13030167.x CrossRefGoogle Scholar
  4. 4.
    Nicolaides KH, Sebire N, Snijders RJM (1999) Die Ultraschalluntersuchung der. Schwangerschaftswoche. Pathenon Publishing, Birmingham, pp 11–14Google Scholar
  5. 5.
    Snijders RJM, Noble P, Sebire N, Souka A, Nicolaides KH (1998) UK multicentre project on assessment of risk of trisomy 21 by maternal age and fetal nuchal translucency thickness at 10–14 weeks of gestation. Lancet 351:343–346. doi:10.1016/S0140-6736(97)11280-6 CrossRefGoogle Scholar
  6. 6.
    Spencer K, Souter V, Tul N, Snijders RJM, Nicolaides KH (1999) A Screening program for trisomy 21 at 10–14 weeks using fetal nuchal translucency, maternal serum free β-human chorionic gonadotropin an pregnancy-associated plasma protein-A. Ultrasound Obstet Gynecol 13:231–237. doi:10.1046/j.1469-0705.1999.13040231.x CrossRefPubMedGoogle Scholar
  7. 7.
    Wald NJ, Hackshaw AK (1997) Combining ultrasound and biochemistry in first-trimester screening for Down’s syndrome. Prenat Diagn 17:821. doi:10.1002/(SICI)1097-0223(199709)17:9<821::AID-PD154>3.0.CO;2-5 CrossRefPubMedGoogle Scholar
  8. 8.
    Schmidt P, Pruggmayer M, Steinborn A, Schippert C, Staboulidou I, Hillemanns P, Scharf A (2007) Are nuchal translucency, pregnancy associated plasma protein-A or free-ß-human chorionic gonadotropin depending on maternal age? A multicenter study of 8116 pregnancies. Arch Gynecol Obstet 276(3):259–262. doi:10.1007/s00404-007-0342-4 CrossRefPubMedGoogle Scholar
  9. 9.
    Schmidt P, Scharf A (2006) Advanced Firsttrimester screening—a critical review of the fundamental studies and suggestions for improvement. Geburtshilfe Frauenheilkd 67:S1–S183Google Scholar
  10. 10.
    Schmidt P, Rom J, Maul H, Vaske B, Hillemanns P, Scharf A (2007) Advanced first trimester screening (AFS): an improved test strategy for the individual risk assessment of fetal aneuploidies and malformations. Arch Gynecol Obstet 276(2):159–166. doi:10.1007/s00404-007-0324-6 CrossRefPubMedGoogle Scholar
  11. 11.
    Hörmansdörfer C, Schmidt P, Hillemanns P, Scharf A (2007) Die pränatale Detektion der Triosomie 13, 18 und 21: Vergleich des Advanced Firsttrimester Screenings (AFS)® mit dem Ersttrimester-Screening nach Nicolaides. Z Geburtshilfe Neonatol 211:243–249. doi:10.1055/s-2007-981361 CrossRefPubMedGoogle Scholar
  12. 12.
    Schmidt P, Hörmansdörfer C, Pruggmayer M, Schütte C, Neumann A, Gerritzen A, Vaske B, Hillemanns P, Scharf A (2008) Improved prenatal aneuploidy screening using the novel ‘Advanced First Trimester Screening’ algorithm—a multicenter study of 10,017 pregnancies. J Clin Ultrasound 36(7):397–402. doi:10.1002/jcu.20509 CrossRefPubMedGoogle Scholar
  13. 13.
    Schmidt P, Hörmansdörfer C, Hillemanns P, Scharf A (2007) Presentation of a novel computer software for the Advanced Firsttrimester Screening. Geburtshilfe Frauenheilkd 68:899Google Scholar
  14. 14.
    Palomaki GE, Haddow JE (1987) Maternal serum alpha-fetoprotein, age, and Down syndrome risk. Am J Obstet Gynecol 156(2):460–463PubMedGoogle Scholar
  15. 15.
    Scharf A, Schmidt P, Seppelt M, Maul H, Wüstemann M, Sohn C (2003) Comparison of risk calculation for trisomy 21 by Nicolaides with a novel software: retrospective analysis of 744 cases. Geburtshilfe Frauenheilkd 63:148–152. doi:10.1055/s-2003-37465 Google Scholar
  16. 16.
    Schmidt P, Staboulidou I, Soergel P, Wüstemann M, Hillemanns P, Scharf A (2007) Comparison of Nicolaides’ risk evaluation for Down’s syndrome with a novel software: an analysis of 1463 cases. Arch Gynecol Obstet 275(6):469–474. doi:10.1007/s00404-006-0288-y CrossRefPubMedGoogle Scholar
  17. 17.
    Schmidt P, Scharf A, Hörmansdörfer C, Elsässer M, Hillemanns P (2007) Different calculation methods for first trimester screening. Frauenarzt 48(11):1089–1092Google Scholar
  18. 18.
    Snijders RJM, Sebire NJ, Cuckle H, Nicolaides KH (1995) Maternal age and gestational age-specific risks for chromosomal defects. Fetal Diagn Ther 10:356–367CrossRefPubMedGoogle Scholar
  19. 19.
    Malone FD, Canick JA, Ball RH, Nyberg DA, Comstock CH, Bukowski R, Berkowitz RL, Gross SJ, Dugoff L, Craigo SD, Timor-Tritsch IE, Carr SR, Wolfe HM, Dukes K, Bianchi DW, Rudnicka AR, Hackshaw AK, Lambert-Messerlian G, Wald NJ, D’Alton ME (2005) First- and second-trimester evaluation of risk (FASTER) Research Consortium. First-trimester or second-trimester screening, or both, for Down’s syndrome. N Engl J Med 353(19):2001–2011CrossRefPubMedGoogle Scholar
  20. 20.
    Bindra R, Heath V, Liao A, Spencer K, Nicolaides KH (2002) One-stop clinic for assessment of risk for trisomy 21 at 11–14 weeks: a prospective study of 15 030 pregnancies. Ultrasound Obstet Gynecol 20(3):219–225. doi:10.1046/j.1469-0705.2002.00808.x CrossRefPubMedGoogle Scholar
  21. 21.
    O’Leary P, Breheny N, Dickinson JE, Bower C, Goldblatt J, Hewitt B, Murch A, Stock R (2006) First-trimester combined screening for Down syndrome and other fetal anomalies. Obstet Gynecol 107(4):869–876PubMedGoogle Scholar
  22. 22.
    Nicolaides KH, Spencer K, Avgidou K, Faiola S, Falcon O (2005) Multicenter study of first-trimester screening for trisomy 21 in 75 821 pregnancies: results and estimation of the potential impact of individual risk-orientated two-stage first trimester screening. Ultrasound Obstet Gynecol 25(3):221–226. doi:10.1002/uog.1860 CrossRefPubMedGoogle Scholar
  23. 23.
    Crossley JA, Aitken DA, Cameron AD, McBride E, Connor JM (2002) Combined ultrasound and biochemical screening for Down’s syndrome in the first trimester: a Scottish multicentre stuy. BJOG 109(6):667–676. doi:10.1111/j.1471-0528.2002.01394.x CrossRefPubMedGoogle Scholar
  24. 24.
    Spencer K, Spencer CE, Power M, Dawson C, Nicolaides KH (2003) Screening for chromosomal abnormalities in the first trimester using ultrasound and maternal serum biochemistry in a one-stop clinic: a review of three years prospective experience. BJOG 110(3):281–286. doi:10.1046/j.1471-0528.2003.02246.x CrossRefPubMedGoogle Scholar
  25. 25.
    Hadlow NC, Hewitt BG, Dickinson JE, Jacoby P, Bower C (2005) Community-based screening for Down’s Syndrome in the first trimester using ultrasound and maternal serum biochemistry. BJOG 112(11):1561–1564. doi:10.1111/j.1471-0528.2005.00722.x CrossRefPubMedGoogle Scholar
  26. 26.
    Wapner R, Thom E, Simpson JL et al (2003) First-trimester screening for trisomies 21 and 18. N Engl J Med 349(15):1405–1413. doi:10.1056/NEJMoa025273 CrossRefPubMedGoogle Scholar
  27. 27.
    Wojdemann KR, Shalmi AC, Christiansen M et al (2005) Improved first-trimester Down syndrome screening performance by lowering the false-positive rate: a prospective study of 9941 low-risk women. Ultrasound Obstet Gynecol 25:227–233. doi:10.1002/uog.1834 CrossRefPubMedGoogle Scholar
  28. 28.
    Muller F, Benattar C, Audibert F, Roussel N, Dreux S, Cuckle H (2003) First-trimester screening for Down syndrome in France combining fetal nuchal translucy measurement and biochemical markers. Prenat Diagn 23(10):833–836. doi:10.1002/pd.700 CrossRefPubMedGoogle Scholar
  29. 29.
    Stenhouse EJ, Crossley JA, Aitken DA, Brogan K, Cameron AD, Connor JM (2004) First-trimester combined ultrasound and biochemical screening for Down syndrome in routine clinical practice. Prenat Diagn 24:774–780. doi:10.1002/pd.980 CrossRefPubMedGoogle Scholar
  30. 30.
    Schuchter K, Hafner E, Stangl G, Metzenbauer M, Hofinger D, Philipp K (2002) The first trimester ‘combined test’ for the detection of Down syndrome pregnancies in 4939 unselected pregnancies. Prenat Diagn 22(3):211–215. doi:10.1002/pd.288 CrossRefPubMedGoogle Scholar
  31. 31.
    Perni SC, Predanic M, Kalish RB, Chervenak FA, Chasen ST (2006) Clinical use of first-trimester aneuploidy screening in a United States population can replicate data from clinical trials. Am J Obstet Gynecol 194(1):127–130. doi:10.1016/j.ajog.2005.06.068 CrossRefPubMedGoogle Scholar
  32. 32.
    Schielen PC, van Leeuwen-Spruijt M, Belmouden I, Elvers LH, Jonker M, Loeber JG (2006) Multi-centre first-trimester screening for Down syndrome in the Netherlands in routine clinical practice. Prenat Diagn 26(8):711–718. doi:10.1002/pd.1486 CrossRefPubMedGoogle Scholar
  33. 33.
    von Kaisenberg CS, Gasiorek-Wiens A, Bielicki M, Bahlmann F, Meyberg H, Kossakiewicz A et al (2002) Screening for trisomy 21 by maternal age, fetal nuchal translucency and maternal serum biochemistry at 11–14 weeks: a German multicenter study. J Matern Fetal Neonatal Med 12(2):89–94. doi:10.1080/713605621 Google Scholar
  34. 34.
    Soergel P, Pruggmayer M, Schwerdtfeger R, Mühlhaus K, Scharf A (2006) Screening for Trisomy 21 with Maternal Age, Fetal Nuchal Translucency and Maternal Serum Biochemistry at 11–14 Weeks: A Regional Experience from Germany. Fetal Diagn Ther 21(3):264–268. doi:10.1159/000091353 CrossRefPubMedGoogle Scholar
  35. 35.
    Scott F, Peters H, Bonifacio M et al (2004) Prospective evaluation of a first trimester screening program for Down syndrome and other chromosomal abnormalities using maternal age, nuchal translucency and biochemistry in an Australian population. Aust N Z J Obstet Gynaecol 44(3):205–209. doi:10.1111/j.1479-828X.2004.00205.x CrossRefPubMedGoogle Scholar
  36. 36.
    Schmidt P (2009) Non-invasive screening methods for chromosomal aberrations in early pregnancy. In: Columbus (ed) Aneuploidy: common forms, mechanisms and detection. Nova Publishing, Hauppauge (accepted)Google Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Peter Schmidt
    • 1
    • 3
  • C. Hörmansdörfer
    • 1
  • M. Golatta
    • 2
  • A. Scharf
    • 2
  1. 1.Department for Gynecology and ObstetricsMedical University of HannoverHanoverGermany
  2. 2.Women’s HospitalUniversity of HeidelbergHeidelbergGermany
  3. 3.WolfenbüttelGermany

Personalised recommendations