First-trimester contingent screening for trisomies 21, 18 and 13 by fetal nuchal translucency and ductus venosus flow and maternal blood cell-free DNA testing

Objective: To examine performance of screening for major trisomies by a policy of first-line assessment of risk according to maternal age, fetal nuchal translucency thickness (NT) and ductus venosus pulsatility index for veins (DV-PIV) followed by cell-free DNA (cfDNA) testing in pregnancies with an intermediate risk.

Methods: We estimated the distribution of risks based on maternal age, fetal NT and DV-PIV in a dataset of 86 917 unaffected and 491 trisomic pregnancies undergoing prospective screening for trisomies. Performance of screening for trisomies by cfDNA testing was derived from a meta-analysis of clinical validation studies. We estimated performance and cost of screening for trisomies using different combinations of ultrasound screening and cfDNA testing.

Results: Screening for trisomies 21, 18 and 13 according to a combination of maternal age, fetal NT and DV-PIV in all pregnancies, followed by invasive testing in the high-risk group (≥1:10) and cfDNA testing in the intermediate-risk group (1:11 – 1:3000) can potentially detect about 96%, 95% and 91% of cases, respectively, with a false-positive rate (FPR) of 0.8%. On the assumption that the costs for ultrasound screening, cfDNA testing and invasive testing are € 150, € 500 and € 1000, respectively, the overall cost of such a policy would be about € 250 per patient. The alternative policy, of universal screening by cfDNA testing, can potentially detect about 99%, 97% and 92% of cases of trisomies 21, 18 and 13, but at an overall cost of more than € 500 per patient.

Conclusion: Incorporation of cfDNA testing into a contingent policy of early screening for the major trisomies, based on the risk derived from first-line screening by a combination of maternal age, fetal NT and DV-PIV, can detect a high proportion of affected cases with a low FPR.