LAUSR

OBJECTIVE To compare the detection rate for trisomy 21 of universal cell free DNA (cfDNA) screening with contingent screening. METHODS Retrospective study at 3 German centers. The study included euploid and trisomy 21 pregnancies where cfDNA and first trimester (FT) screening assessment was carried out. The FT risk for trisomy 21 was computed based on combined screening and stratified into the following classes: high risk >1:10, intermediate risk 1:11 - 2,500, low risk <1:2,500. For universal cfDNA screening, the cfDNA test results were examined. For the contingent screening model, the result of the cfDNA test was taken into account in case of an intermediate FT risk. Different strategies combining maternal age, nuchal translucency, nasal bone, beta-hCG and PAPP-A were evaluated. Screen-positivity was defined as either a high risk after first trimester screening or a cfDNA test indicating a high risk result. An inconclusive cfDNA test was also considered as screen positive. RESULTS The search of the database identified 2,255 euploid and 163 affected pregnancies. All affected fetuses were identified by universal cfDNA screening. 1.3% of the euploid fetuses were classified as screen positive due to final inconclusive cfDNA test result. The detection and false positive rate of a contingent approach that is based on combined screening and cfDNA screening in the intermediate group would be 98.4% and 0.7%, respectively. With this approach, cfDNA screening would be necessary in only about 27% of all pregnancies. CONCLUSION This study demonstrates that a contingent approach provides similar detection rates for trisomy 21 as universal cfDNA screening, by reducing in 73% the number of cfDNA tests.