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.