Contingent cfDNA Screening Implementation: Increasing Diagnostic Accuracy and Reducing Invasive Testing – 6 Years’ Results in a Single Center

Abstract

Objectives: In 2018, a contingent screening program was implemented in the community of Castilla y Leon (Spain). This study aimed to compare the results achieved in the University Hospital of Salamanca during the three years of contingent screening (2018-2020) with those of the previous three years (2015-2017) to assess the modification in the rate of trisomies detection and the number of invasive tests. Methods: A total of 9903 singleton pregnancies without malformations nor nuchal translucency >p99 were included. 5165 patients underwent combined screening and 4738 had contingent screening based on the combined test risk. In the combined test group, women were offered an invasive test if the risk was ≥1:270 whilst risks under 1:270 were considered low risks, and no further testing was offered. In the contingent screening group, invasive testing was offered if the risk was ≥1:100 (≥1:50 from 2020 onwards) whilst cfDNA was offered if the combined test risk was between 1:100 to 1:1000 (1:50-1:1000 from 2020 onwards). When risk was <1:1000, no further testing was offered. Results: There were 30 cases of trisomy 21 throughout the 6 years of study. 4 cases had risks <1:270 and were diagnosed by cfDNA. Risk >1:1000 threshold for contingent test detected 100% T21. There were no false-negative results. "No-call" cfDNA results were minimized by repeating blood collection two weeks later, as fetal fraction was doubled. Invasive testing had a drop rate of 84% after contingent screening implementation. Discussion: The implementation of population-based contingent screening significantly reduces the number of invasive tests without lowering diagnostic accuracy. To achieve the maximum efficiency of the program, it is important to know the best cut-offs according to the population where the program is to be implemented. The number of uninformative results due to low fetal fraction (FF) can be reduced by repeating the test 2 weeks after the initial extraction: this increases the FF to twice the initial one, achieving informative results and avoiding unnecessary invasive tests.