Combined Sonographic and Biochemical Markers for Down Syndrome Screening

Objective . To evaluate the efficacy of fetal nuchal fold thickness and proximal long bone biometric measurements in modifying Down syndrome serum screening risk in a population of women referred for second‐trimester sonography. Methods . Sonographic biometric measurements and biochemical markers were combined retrospectively for 2533 women with known pregnancy outcomes. Four different screening methods were compared: (1) advanced maternal age; (2) biochemical serum screening markers; (3) modification of serum screening risks on the basis of categorical cutoffs for nuchal fold and femur and humerus length; and (4) a combined approach in which the sonographic measurements were treated as multiples of the medians and entered, together with the serum screening results, into a multivariable algorithm. The efficacy was compared at second‐trimester risk cutoffs of 1:270 and 1:100. Results . Down syndrome was present in 30 of the 2533 pregnancies (1 in 84). With the use of the 1:270 cutoff, biochemical screening had 93% sensitivity and a 40% false‐positive rate. With application of the categorical method of fixed cutoffs to incorporate fetal biometry, the false‐positive rate was reduced to 33% with no loss of sensitivity. The combined model had 83% sensitivity and a 19% false‐positive rate. The combined method had the highest positive predictive value (1 in 20). Similar gains in efficacy could be shown with the 1:100 cutoff. Conclusions . For this high‐risk group, the multivariate model that combines serum screening and sonography can result in a substantial reduction in the number of amniocenteses. Although the addition of the sonographic biometric measurements resulted in some Down syndrome cases being missed, the net effect was a large improvement in the overall positive predictive value of the screening.