A comparison of first trimester prenatal screening strategies for Down Syndrome with maternal age and preferences considerations

Objective: Screening for Down Syndrome (DS) includes traditional ultrasound and serum-based and cell-free DNA (cfDNA) testing. While cfDNA testing usually has superior performance, it is significantly more costly. As an alternative, a hybrid strategy combining contingent cfDNA with traditional testing is recommended when universal cfDNA screening is not feasible. This study compares the efficacy of traditional, contingent cfDNA, and universal cfDNA screening strategies at various cut-offs based on maternal age and parents' preferences, which may improve testing outcomes and patients' satisfaction. Method: Decision trees were used to analyze a cohort of 3 855 500 pregnancies from 12 to 50 years old. The performance of the strategies was compared using the number of adverse outcomes (undetected DS live births and euploid procedure-related losses). Results: Universal cfDNA results in the fewest number of adverse outcomes in every scenario. Contingent cfDNA performs better than traditional screening when the cut-offs used to identify high-risk cases for cfDNA testing are relatively low. These cut-offs change depending on the maternal age and parents' preference. Conclusion: Maternal age and parents' preferences should be considered when choosing cut-offs for contingent cfDNA to remain as an effective strategy compared to traditional screening and to improve patient satisfaction.