Expected performance of second trimester maternal serum testing followed by a 'genetic sonogram' in screening of fetal Down syndrome.

OBJECTIVE: To assess the efficacy of screening for fetal Down syndrome through the sequential provision of second trimester maternal serum tests and fetal ultrasound (the 'genetic sonogram').

METHODS: Monte Carlo modeling was used to generate typical results for second trimester serum screening. Serum test likelihood ratios were then multiplied by likelihood ratios associated with the provision of a genetic sonogram. The impact of adding the genetic sonogram on the detection rate (DR) and false-positive rate (FPR) were assessed for typical protocols that are currently in use. The effect of expanding the number of women who receive the genetic sonogram, variation in the marker frequencies in the genetic sonogram, and a multivariate Gaussian model that incorporated both serum and ultrasound measurements as continuous variables were also considered.

RESULTS: When the genetic sonogram is offered only to those women who are screen-positive by serum testing, there can be a substantial reduction in the number of women with an indication for amniocentesis but also some loss in detection. The extent of these changes will partially depend on the serum tests and cutoff used. Providing the genetic sonogram to more women can reduce loss in detection without resulting in high amniocentesis rates. As a sequential screening tool, the genetic sonogram can be improved by incorporating markers that have a high frequency in affected pregnancies and by using ultrasound measurements as continuous variables.

CONCLUSION: It should be possible to provide highly effective multistep screening protocols that maximize the benefits of both maternal serum and ultrasound while minimizing the amount of testing offered.