Risk of Down syndrome and any clinically significant chromosome defect in pregnancies with abnormal triple-screen and normal targeted ultrasonographic results

OBJECTIVE: Our purpose was to study prospectively the use of ultrasonographic biometry to refine the risk estimates for both Down syndrome and any clinically significant chromosome defect in women with abnormal biochemical triple-screen results. STUDY DESIGN: Ultrasonographic biometry and anatomic survey were performed on study and control cases. Expected values for humerus, femur combined humerus plus femur lengths, and abdominal circumference were generated on the basis of biparietal diameter obtained from a normal group. Threshold observed/expected values of each measurement for screening for Down syndrome and clinically significant chromosome defects were determined with receiver-operator characteristic curves. By stepwise logistic regression analysis the optimal screening parameters, including nuchal thickness, for detection of Down syndrome and clinically significant chromosome defect were determined. Risk tables for chromosome anomalies were developed on the basis of ultrasonography and triple-screen values. RESULTS: Of 1034 cases at risk for Down syndrome (risk greater than or equal to 1/270) or trisomy 18 on the basis of triple-screen results, there were 11 cases of Down syndrome, 1 of trisomy 18, and 17 clinically significant chromosome defects, Abnormal nuchal thickness or observed/expected humerus length <0.92 was the most sensitive parameter for Down syndrome detection. Abnormal nuchal thickness or observed/expected combined femur and humerus length <0.90 was the most sensitive for significant chromosome defects, With abnormal biometry or anatomy the Down syndrome risk was 8 of 127 versus 1 of 753 in normals, odds ratio 50.4 (95% confidence interval 6.4 to 90.2), p < 0.00001, and the risk of significant defects was 11 of 90 versus 6 of 830 in normals, odds ratio 19.3 (95% confidence interval 6.4 to 60.5), p < 0.00001, In a pregnancy with a 1 in 270 triple-screen risk for Down syndrome, normal biometric and anatomic results reduce the risk to 1 in 2100. CONCLUSION: Normal ultrasonographic anatomy and biometry significantly reduces the risk of both Down syndrome and any significant chromosome defects in pregnancies with abnormal triple-screen results.