The concept of a 3D firsttrimester screening cut-off

Objective: In classical firsttrimester screening according to Nicolaides a common age-depending backgroundrisk for trisomy 21 is modified by likelihood ratios to result in a so called 'adjusted risk'. At a cut-off of 1: 300 the resulting risk is considered as suspicious and an invasive testing should follow.

Materials and methods: The measurement values can be visualized in a 3 dimensional scatter plot. The concept of a 3D risk assessment is based on the fact that chromosomal aberrations offer a typical constellation of elevated NT, lowered Papp-A and increased (trisomy 21) or decreased (trisomy 18, 13) fß-hCG. In fact, other findings are rare and most of these fetuses are healthy. In this concept paper we suggest to use 3D spaces of the scatter plot to obtain a risk assessment. Thereby a sharp non-linear boundary can be determined. In a first analysis 10,116 pregnancies were analyzed and the testperformance parameters were compared with those by classical firsttrimester screening.

Results: Eighty-fife cases of aneuploidy were found in this cohort. Thereof 73 were detected by both, the classical firsttrimester screening and this new concept. The false positive rate could be lowered from 644 to 220 (-65.8% (!), p<0.001). Therewith the specificity rises from 93.5 to 97.8% at an equal sensitivity of 84.7%.

Discussion: To get a valid risk assessment a large number of screenings with known fetal outcome is recquired. Especially in regions with rare constellations this is quite challanging, so an international multicenter study is beeing initiated. Interested centers please contact [e-mail].