Enhanced First Trimester Screening for Trisomy 21 with Contingent Cell-Free Fetal DNA: A Comparative Performance and Cost Analysis

Abstract

Objective: Prenatal screening for trisomy 21 is a standard of care. Emerging cell-free fetal DNA (cffDNA) technologies can improve screening performance, but they are expensive. This study was conducted to propose a contingent screening model that would incorporate cffDNA technology, would remain affordable, and could be applied equitably in a publically funded system.

Methods: Using performance and cost parameters from published literature, four prenatal screening strategies were compared. Scenario 1 modelled integrated prenatal screening (first trimester nuchal translucency and biochemical markers from both the first and second trimesters) with no cffDNA. Scenarios 2 and 3 modelled first trimester combined screening (FTS) and "enhanced FTS" (adding serum placental growth factor and alpha fetoprotein to FTS), respectively, with contingent cffDNA following a positive result. Scenario 4 modelled cffDNA as the primary screening test.

Results: Scenario 1 provides a known detection rate (DR) of 88%, with a false positive rate (FPR) of 3.3%. Scenarios 2 and 3 result in a DR of 94% and overall FPR of 0.59% and 0.33%, respectively, comparable to the DR of 96% and FPR of 0.1% with primary cffDNA (assuming the published test failure rate of 3%). The total cost, cost per woman screened, and cost per case of trisomy 21 detected were lower with scenario 3 (enhanced FTS with contingent cffDNA) compared with primary cffDNA or scenario 2 (FTS with contingent cffDNA).

Conclusion: Enhanced FTS with contingent cffDNA following a positive result provides a similar performance to that of primary cffDNA at a substantially lower cost.

Keywords: Prenatal screening; cell-free fetal DNA test; enhanced first trimester screening; first trimester combined screening; trisomy 21.