Clinical and Economic Evaluation after Adopting Contingent Cell-Free DNA Screening for Fetal Trisomies in South Spain.

INTRODUCTION: Contingent cell-free (cf) DNA screening on the basis of the first-trimester combined test (FCT) results has emerged as a cost-effective strategy for screening of trisomy 21 (T21). OBJECTIVES: To assess performance, patients' uptake, and cost of contingent cfDNA screening and to compare them with those of the established FCT. METHODS: This is a prospective cohort study including all singleton pregnancies attending to their FCT for screening of T21 at 2 university hospitals in South Spain. When the FCT risk was ≥1:50, there were major fetal malformations, or the nuchal translucency was ≥3.5 mm, women were recommended invasive testing (IT); if the risk was between 1:50 and 1:270, women were recommended cfDNA testing; and for risks bellow 1:270, no further testing was recommended. Detection rate (DR), false-positive rate (FPR), patients' uptake, and associated costs were evaluated. RESULTS: We analyzed 10,541 women, including 46 T21 cases. DR of our contingent strategy was 89.1% (41/46) at 1.4% (146/10,541) FPR. Uptake of cfDNA testing was 91.2% (340/373), and overall IT rate was 2.0%. The total cost of our strategy was €1,462,895.7, similar to €1,446,525.7 had cfDNA testing not been available. CONCLUSIONS: Contingent cfDNA screening shows high DR, low IT rate, and high uptake at a similar cost than traditional screening.

Does a High-Risk (>1/50) Result for First-Trimester Combined Screening Always Entail Invasive Testing? Which Patients from This Group Might Benefit from cfDNA Testing?

Currently, cell-free DNA (cfDNA) is offered as part of a contingent screening for patients with a first-trimester combined test (FCT) risk between 1/50 and 1/250. However, most aneuploidies are within the group of patients with a risk above 1/10. An observational, retrospective, and multi-centric study was carried out, to evaluate the theorical performance of lowering the cut-off point for the high-risk group from 1/50 to 1/10. Out of the 25,920 patients included, 25,374 (97.9%) consented to the cfDNA contingent screening for aneuploidies. With the proposed strategy, knowing that the detection rate (DR) of cfDNA testing for trisomy 21 is 99.7%, the DR for trisomy 21 would have stayed in a 93.2%, just as it was with the current strategy. In this instance, 267 (1.1%) invasive tests would have been performed, while the current strategy had a total of 307 (1.2%). The false positive rate (FPR) rate would have stayed at 5.2% in both scenarios. In conclusion, the contingent screening of aneuploidies based in the result of the FCT, offering the analysis of cfDNA to patients with an intermediate risk after lowering the cut-off point from 1/50 to 1/10, is a valid alternative that might maintain the current detection rates and avoid the complications associated with invasive testing.