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Hum. Reprod. Advance Access originally published online on June 10, 2008
Human Reproduction 2008 23(9):1968-1975; doi:10.1093/humrep/den224
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© The Author 2008. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Screening for trisomies 21, 18 and 13 by maternal age, fetal nuchal translucency, fetal heart rate, free β-hCG and pregnancy-associated plasma protein-A

Karl O. Kagan1,2,4, Dave Wright3, Catalina Valencia1, Nerea Maiz1 and Kypros H. Nicolaides1,4

1 Harris Birthright Research Centre for Fetal Medicine, King's College Hospital, Denmark Hill, London SE5 8RX, UK 2 Department of Obstetrics and Gynaecology, University of Tuebingen, Germany 3 Department of Mathematics and Statistics, University of Plymouth, UK

4 Correspondence address. E-mail: kypros{at}fetalmedicine.com.

BACKGROUND: A beneficial consequence of screening for trisomy 21 is the early diagnosis of trisomies 18 and 13. Our objective was to examine the performance of first-trimester screening for trisomies 21, 18 and 13 by maternal age, fetal nuchal translucency (NT) thickness, fetal heart rate (FHR) and maternal serum-free β-hCG and pregnancy-associated plasma protein-A (PAPP-A).

METHODS: Prospective screening for trisomy 21 by maternal age, fetal NT, free β-hCG and PAPP-A at 11+0–13+6 weeks in singleton pregnancies, including 56 376 normal cases, 395 with trisomy 21, 122 with trisomy 18 and 61 with trisomy 13. Risk algorithms were developed for the calculation of patient-specific risks for each of the three trisomies based on maternal age, NT, FHR, free β-hCG and PAPP-A. Detection (DR) and false positive rates (FPR) were calculated and adjusted according to the maternal age distribution of pregnancies in England and Wales in 2000–2002.

RESULTS: The DR and FPR were 90% and 3%, respectively, for trisomy 21, 91% and 0.2% for trisomy 18 and 87% and 0.2% for trisomy 13. When screen positivity was defined by an FPR of 3% on the risk for trisomy 21 in conjunction with an FPR of 0.2% on the maximum of the risks for trisomies 13 and 18, the overall FPR was 3.1% and the DRs of trisomies 21, 18 and 13 were 91%, 97% and 94%, respectively.

CONCLUSIONS: As a side effect of first-trimester screening for trisomy 21, ~95% of trisomy 13 and 18 fetuses can be detected with an 0.1% increase in the FPR.

Key words: nuchal translucency/pregnancy-associated plasma protein-A/serum-free β-hCG/first trimester/trisomy

Submitted on March 20, 2008; resubmitted on May 8, 2008; accepted on May 14, 2008.


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