OBJECTIVE: This study aimed to determine the principal factors contributing to 
the cost of avoiding a birth with Down syndrome by using cell-free DNA (cfDNA) 
to replace conventional screening.
METHODS: A range of unit costs were assigned to each item in the screening 
process. Detection rates were estimated by meta-analysis and modeling. The 
marginal cost associated with the detection of additional cases using cfDNA was 
estimated from the difference in average costs divided by the difference in 
detection.
RESULTS: The main factor was the unit cost of cfDNA testing. For example, 
replacing a combined test costing $150 with 3% false-positive rate and invasive 
testing at $1000, by cfDNA tests at $2000, $1500, $1000, and $500, the marginal 
cost is $8.0, $5.8, $3.6, and $1.4m, respectively. Costs were lower when 
replacing a quadruple test and higher for a 5% false-positive rate, but the 
relative importance of cfDNA unit cost was unchanged. A contingent policy 
whereby 10% to 20% women were selected for cfDNA testing by conventional 
screening was considerably more cost-efficient. Costs were sensitive to cfDNA 
uptake.
CONCLUSION: Universal cfDNA screening for Down syndrome will only become 
affordable by public health purchasers if costs fall substantially. Until this 
happens, the contingent use of cfDNA is recommended.