New Down syndrome screening algorithm. Ultrasonographic biometry and multiple serum markers combined with maternal age

OBJECTIVE: We compared the Down syndrome screening efficiency of a new algo rithm that combines humerus length measurement and serum analytes Versus th at of the traditional triple-analyte serum screen. STUDY DESIGN: Humerus length measurements were obtained prospectively in 17 43 midtrimester(14 to 24 weeks) singleton fetuses before genetic amniocente sis. All patients had triple-marker serum screening before amniocentesis. D ata on humerus length were expressed as multiples of the median, and the di stributions were normalized by log transformation. Backward multiple stepwi se logistic regression analysis was performed to determine which combinatio n of biometry and serum markers best predicted fetal Down syndrome. The scr eening efficiency of the traditional triple-analyte algorithm was compared with that of a new multivariate gaussian algorithm that combined biometry a nd serum markers. RESULTS: There were 31 (1.8%) fetuses with Down syndrome in the study popul ation. In the regression analysis humerus length, human chorionic gonadotro pin, alpha-fetoprotein, and maternal age were significant predictors of Dow n syndrome, but unconjugated estriol was not. The combined algorithm (humer us length, human chorionic gonadotropin, and alpha-fetoprotein and age) was superior to the traditional triple screen for Down syndrome detection. The sensitivities at fixed false-positive rates were consistently higher in th e combination than in the triple-screen protocol. For example, at a 10% fal se-positive rate the sensitivities were 65.0% and 52.3%, respectively. Simi larly, at a 15% false-positive rate the sensitivities were 73.5% and 55.0%, respectively. CONCLUSION: A new screening algorithm combining humerus length and serum an alytes was superior to the traditional triple screen. Although we used a hi gh-risk population in this study, it is expected that the observed superior ity of the combination screen would persist in a population of younger wome n. The development of a combined biometric and serum analyte screening algo rithm for estimating individual odds could represent an advance in prenatal Down syndrome screening.