Combined ultrasound biometry, serum markers and age for Down syndrome riskestimation

Objective To compare Down syndrome screening efficiency of the standard ser um triple analyte screen to that of a four-component screen consisting of u ltrasound biometry and serum markers in the second trimester. Methods The Down syndrome screening efficiency of the triple screen, i.e. a lpha-fetoprotein (AFP), unconjugated estriol (E3), hCG and maternal age, wa s compared with the four-marker algorithm, i.e. humerus length, nuchal thic kness, AFP and hCG plus maternal age. A quadrivariate Gaussian algorithm wa s used to calculate individual Down syndrome odds. Receiver operating chara cteristic (ROC) curves plotting sensitivity against false-positive rate wer e constructed for each algorithm and the areas under the curves were compar ed to determine which was superior Sensitivity and false-positive rates at different Down syndrome risk thresholds were also compared. Results There were 46 cases of Down syndrome (1.9%) with 2391 normal single ton pregnancies in a referral population in which triple screen, fetal biom etry and karyotype had been done. The gestational age range for the study w as 14-24 completed weeks. The median maternal age for the study group was 3 5.0 years (14.0-46.0 years). The areas (SE) under the ROC curves were 0.75( 0.04) and 0.93(0.02) for the standard triple and the four-marker screen, re spectively (P < 0.001). At a 10% false-positive rate, detection was 45.7% f or the triple and 80.4% for the four-marker screen. Conclusions A new algorithm combining humerus length and nuchal thickness m easurement with serum AFP, hCG and maternal age substantially improved Down syndrome screening efficiency compared with the traditional triple screen. The model appears promising and should be evaluated in an independent data set.