Combined use of genetic sonography and maternal serum triple-marker screening: an effective method for increasing the detection of trisomy 21 in women younger than 35 years

Abstract

Objective: The current standard of practice is to screen women younger than 35 years for trisomy 21 with maternal triple-marker screening, followed by amniocentesis in high-risk (1:10-1:190) patients. Non-high-risk patients are not offered further diagnostic testing. This study was conducted to determine whether genetic sonography of fetuses considered to be at moderate risk (1:190-1:1000) after maternal triple-marker screening increases the detection for trisomy 21, is cost-effective, and reduces the number of amniocenteses required to detect a single fetus with trisomy 21.

Methods: After triple-marker screening, mathematical modeling was used to classify 500,000 theoretical fetuses as high, moderate, or low risk (>1:1001-1:10,000) for trisomy 21. The sensitivity for genetic sonography varied between 60% and 90%, and false-positive rates varied between 5% and 25%. Two programs (I and II) were compared with the control program. The control program included patients with high-risk fetuses (1:10-1:190) who had amniocentesis. Program I consisted of patients in the moderate-risk group (1:191-1:1000) who had genetic sonography followed by amniocentesis only when an abnormal sonographic finding was present. Program II used an approach in which genetic sonography was done for both high- and moderate-risk fetuses, and amniocentesis was performed only when an abnormal sonographic finding was present.

Results: When added to the control program, genetic sonography significantly increased the detection rate of Down syndrome (range, 68.1%-77.8% versus 49%), reduced the cost of detection, and resulted in a ratio of fetuses with Down syndrome detected to normal fetuses lost because of amniocentesis of greater than 1 (range, 2.1-4.2). Compared with the control program, program II significantly increased the detection of fetuses with trisomy 21 (range, 56%-72%) when the sensitivity of genetic sonography was >70%, reduced the cost of detection, and had ratios of trisomy 21 detection to normal fetuses lost because of amniocentesis of between 2.38 and 17.88.

Conclusion: Women younger than 35 years and classified as having moderate risk after triple-marker screening could undergo genetic sonography under 1 of 2 approaches, either of which would result in an increased detection rate of trisomy 21 and be cost-effective without increasing the loss rate of normal fetuses after genetic amniocentesis.