Ultrasound Screening of Fetuses at Increased Risk for Down Syndrome: How Many Missed Diagnoses?

Abstract

Certain major structural anomalies found on sonography—notably cardiac anomalies and duodenal atresia—are associated with Down syndrome (DS), and numerous “soft markers” also have been identified. As a result, some physicians and patients consider a second-trimester sonogram to be a screening test for DS. Most commonly, women who have already been identified as being at increased risk, either because of advanced maternal age or a positive serum screening test, undergo a second-trimester ultrasound examination, and only those high-risk women who also have sonographic markers of fetal DS choose amniocentesis. Alternatively, low-risk women may request an ultrasound examination as their primary screening test and forgo other screening strategies such as first- or second-trimester maternal serum screening. Most sonographic markers, however, have low positive predictive value for DS. To determine whether different sensitivities, false-positive or -negative rates, or amniocentesis-related pregnancy loss rates would make ultrasound a more effective screening tool, the investigators designed a decision analysis model for women at increased risk of having a fetus with DS. A policy of offering amniocentesis to all women at increased risk by virtue of maternal age or maternal serum screening was compared with one specifying amniocentesis only when high-risk women also had sonographic markers of fetal DS. The sonographic detection rate and screen-positive rate were varied from 40% to 90% and 5% to 30%, respectively, and the amniocentesis-related pregnancy loss rate was assumed to be one in 200. Using targeted ultrasonography to determine which high-risk women should have an amniocentesis, 56% of 7025 fetuses with DS would be missed. Among women at highest risk (both advanced maternal age and positive serum screening results), the detection rate for serum screening would be 89%, but adding sonography reduced this rate to 54%. Even when the sonographic detection rate has increased to 80% and the screen-positive rate was reduced to 10%, 42% of all DS cases would be missed. Many women with normal sonographic findings remain at high risk of having a fetus with DS. Using ultrasound adjunctively in high-risk women will result in many cases being missed. At present, at least, ultrasonography is insufficiently sensitive to rule out a fetus with DS in women at risk. Women who are not certain about whether to have amniocentesis because of possible complications should have an opportunity to inquire about the benefits and risks of ultrasound for the detection of DS as well as the risk of procedure-related fetal loss.