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False-positive rates in screening for trisomies 18 and 13: a comparison between first-trimester combined screening and a cfDNA-based approach

  • Karl Oliver Kagan
  • Jiri Sonek
  • Andreas Sroka
  • Harald Abele
  • Philipp Wagner
  • Natalia Prodan
  • Markus Hoopmann
Maternal-Fetal Medicine
  • 29 Downloads

Abstract

Purpose

To determine the false-positive rates (FPR) associated with screening for trisomy 18/13 using first-trimester combined screening (FTCS) and an ultrasound plus cfDNA-based approach (US-cfDNA), which includes a detailed ultrasound examination, a cfDNA analysis and a FTCS reflex backup test for cases with uninformative results.

Methods

This is a sub-analysis of a randomized controlled trial, which was performed between 2015 and 2016. Pregnant women with a normal first-trimester ultrasound examination at 11–13 weeks’ gestation (NT < 3.5 mm, no anomalies) were randomized into two groups: FTCS and US-cfDNA screening. The overall FPR in screening for trisomies 18/13 and 21 was compared with the FPR in screening for trisomy 21 alone. Pregnancies were considered screen positive if the risk for trisomy 21 was 1:100 and for trisomy 18 and 13, 1:20 each.

Results

The study population consisted of 688 pregnancies in each study arm. In the FCTS group, median delta NT was 0.0 mm, free beta-hCG and PAPP-A 0.96 and 1.11 MoM. In the US-cfDNA group, median delta NT was 0.0 mm. In 10 pregnancies, the cfDNA analysis was uninformative. In the FTCS and in the US-cfDNA group, the FPR in screening for trisomy 21 was 2.5% and 0%. In both groups, the overall FPR was not increased by adding screening algorithms for trisomies 18 and 13.

Conclusion

In conclusion, the addition of screening for trisomies 18 and 13 to screening for trisomy 21 does not significantly change FPR. This is true for both the FTCS and the US-cfDNA-based approach.

Keywords

Aneuploidy First trimester Nuchal translucency cfDNA Trisomies 18 and 13 

Notes

Author contributions

KOK: conceptualization, project development, formal analysis, funding acquisition, project administration, manuscript writing and editing; JS: manuscript writing and editing; AS: formal analysis; HA: formal analysis; PW: data collection and analysis; NP: data analysis; MH: manuscript writing and editing.

Funding

The study was supported by Cenata GmbH (Tübingen, Germany) and Roche Inc. (San Jose, CA, USA). The cell free DNA tests in the prospective arm of the study were carried out without additional costs.

Compliance with ethical standards

Conflict of interest

All authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This is a secondary analysis of a randomized controlled study at the University of Tübingen. Approval for the prospective study was obtained from the local ethics committee (no. 572/2015BO1). The original study was registered in the International Standard Randomized Controlled Trial Number registry (ISRCTN no. 11174071). Approval for the retrospective study was also obtained from the local ethics committee (no. 531/2018BO2).

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Women’s HealthUniversity Women’s Hospital TuebingenTübingenGermany
  2. 2.Fetal Medicine Foundation USADaytonUSA
  3. 3.Division of Maternal-Fetal MedicineWright State UniversityDaytonUSA

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