Clinical implementation of first trimester combined test for aneuploidies in patients aged 35 years or older

Abstract

Introduction Down Syndrome (DS) is the most common chromosomal abnormality and the risk to have an affected baby relates directly to maternal age. Invasive prenatal diagnosis based on advanced maternal age (AMA) alone is still a large contributor to invasive testing (amniocentesis and villocentesis). However, there are many reasons to abandon screening on the basis of AMA, given its low detection rate (DR), the risk of fetal loss (0,5-1%) and high costs for the national health systems (NHS). The aim of our study was to evaluate the performance of the first trimester combined screening test (CT) plus markers in women aged 35 years or older.

Materials and methods From February 2016 and September 2018 we prospectively enrolled 493 women aged 35 or older, referred to the Fetal Medicine Clinic Policlinico G. Rodolico University Hospital, Catania Italy. After counseling 259 (52,5%) women chose to have an invasive test (group A) while 234 (47,5%) underwent the CT plus (group B), reserving the right to choose the invasive test after receiving the results.

Results The incidence of DS was similar in both group, 2.3% in group A and 1.7% in group B. The DR for the CT was 100% for a 12.5% of false positive rate (FPR); by the additional use of first trimester markers, the presence of the nasal bone (NB), the evaluation of the ductus venosus blood flow (DV) and tricuspid regurgitation (TR), we were able to reduce the FPR at a value of 2%. During the study period we observed a 19.6% reduction of invasive procedures and a 60% increase in the uptake of CT in women aged 35 or older.

Conclusions The additional use of first trimester markers, NB, DV and TR, is feasible and it reduces FPR without any additional costs for NHS. We provide evidence that adequate Down syndrome screening policy are the best way to reduce the rate of invasive procedures and to improve costeffectiveness. In conclusion this study demonstrates that maternal age is not an appropriate criterion for Down syndrome screening when CT plus is available.