Comparison of first‐trimester contingent screening strategies for Down syndrome

Abstract

To assess the relative performance of a multi-stage first-trimester screening protocol for fetal Down syndrome. Data from 10,767 women who underwent combined ultrasound and biochemistry (BC) screening in the first trimester were reanalyzed using a contingent model approach. Amongst the 10,854 fetuses with known outcome, 32 had Down syndrome, 232 had other abnormalities and 10,590 were unaffected. Nuchal translucency (NT), BC and combined (NT-BC) gestational age-specific risks were calculated for each individual using The Fetal Medicine Foundation risk calculation algorithms (Mixture Model and Biochemistry). Individual patients were categorized as at low, high or intermediate risk according to one of the following three strategies. In 'Strategy-NT-BC' initial screening was performed using both NT and BC. In 'Strategy-BC' initial screening was undertaken using maternal serum markers followed by NT assessment in those with an intermediate risk (1 : 51 < risk <or= 1:1000) while in 'Strategy-NT' initial screening was undertaken using NT followed by serum marker assessment in those with an intermediate risk (1 : 51 < risk <or= 1:1000). The nasal bone was assessed in those with an intermediate risk as the final stage in each of the three strategies. Those with an adjusted risk of 1 in 100 or higher after nasal bone assessment were reclassified as high risk. Detection and false-positive rates were compared between differing strategies in our local population, and this analysis was also performed with the maternal age for our population standardized to the distribution found in England and Wales. In our local population the detection rate for a 5% false-positive rate using a combined screening policy (NT-BC) was 88% (95% CI, 75.3-98.9%), and 2.3% had an absent nasal bone. The respective detection rate and false-positive rate of the three multi-stage screening strategies were: Strategy-NT-BC: 87.5 and 2.5%; Strategy-BC: 87.5 and 5%; Strategy-NT: 84.4 and 2.9%. In the contingent Strategy-BC only 29% of those initially screened using serum markers required an NT scan. If the model were applied to a hypothetical obstetric population standardized to the maternal age distribution in England and Wales, the detection and false-positive rates of the same three screening strategies would be: Strategy-NT-BC: 86.2 and 1.9%; Strategy-BC: 82.8 and 4%; Strategy-NT: 75.8 and 2.3%, respectively. First-trimester contingent screening provides detection and false-positive rates comparable to those achieved using combined screening, but could be used to significantly reduce the number of scans performed.