False positive rate in first trimester screening based on ultrasound and cfDNA vs. first-trimester combined screening with additional ultrasound markers

Objective:

To determine whether screening for trisomy 21 based on first trimester combined screening (FTCS) with assessment of the nasal bone (NB), the tricuspid (TCF) and the ductus-venosus-blood flow (DVF) results in similar false-positive-rates compared to the ultrasound and cfDNA screening.

Methods:

This is a sub-analysis of a prospective randomized controlled study, which was performed between 2015 and 2016. Pregnant women with a normal first-trimester ultrasound examination at 11 to 13 weeks' gestation were randomized into two groups: FTCS with assessment of the NB, TCF and DVF (eFTCS) and ultrasound + cfDNA screening. The false-positive-rate in screening for trisomy 21 was defined as primary outcome parameter.

Results:

The study population consisted of 688 pregnancies in each study arm. In the eFCTS group, median delta NT was 0.0 mm, free beta-hCG and PAPP-A 0.96 and 1.11 MoM and the NB, TCF and DVF PIV abnormal in 0.9%, 0.6% and 7.0% cases. In the ultrasound + cfDNA group, median delta NT was 0.0 mm. In 10 pregnancies, the cfDNA analysis was uninformative and the risk for trisomy 21 was based on eFCTS. There were no false-positive cases in the ultrasound + cfDNA group, the false-positive-rates were between 0.9% and 2.2% with eFTCS.

Conclusion:

Screening for trisomy 21 based ultrasound + cfDNA has a lower false-positive-rate than eFTCS.