Computing the Risk for Down Syndrome When an Abnormal Finding is Present

 A 35 year-old patient declines genetic amniocentesis. However, she desires a Genetic Ultrasound. The ultrasound is performed and an abnormal nuchal skin fold is identified. What is her new risk for trisomy 21.Facts

1. Prior Probability Risk: For trisomy 21 her second trimester risk based upon her age of 35 years is 1:296.

2. Likelihood Ratio for an abnormal nuchal skin fold is 85.2 Computation of the "new risk " or Posterior Probability for Trisomy 21

1. Convert the risk of 1:296 to a decimal by dividing 1/(296 -1)= 0.0034

2. Multiply the second trimester risk converted to a decimal (0.0034) (prior probability) by the likelihood ratio for an abnormal nuchal skin fold (85.2). This will be the "new" or Posterior Probability Risk for trisomy 21.

3. 0.0034 x 85.2 = 0.29

4. Divide 1 by the Posterior Probability Risk to compute the "new" risk for trisomy 21.

5. 1/0.29 = 3.4

6. The risk for trisomy 21 has changed from 1 in 296 to 1 in 3.

 

Computing the Risk for Down Syndrome Following a Normal Genetic Ultrasound

 A 35 year-old patient declines genetic amniocentesis. However, she undergoes maternal serum screening. The results return and have changed her risk from 1 in 296 to 1 in 100. Because she does not desire an amniocentesis and wants additional information regarding her risk for trisomy 21, she requests a Genetic Ultrasound. The ultrasound is normal. What is her new risk for trisomy 21.Facts

1. Prior Probability Risk: 1 in 100 for trisomy 21 following triple marker screening.

2. Sensitivity: Normal ultrasound = 0.90

3. Specificity: Normal ultrasound = 0.94Computation of the "new risk " or Posterior Probability for Trisomy 21

1. Convert the risk of 1:100 to a decimal by dividing 1/(100-1) = 0.01

2. Compute the likelihood ratio for a normal test using the sensitivity and specificity for a normal study. (Note that the equation is different from the one used in cases 1-3 in which an abnormal ultrasound finding was present.) The computation is as follows: (1-Sensitivity) / specificity = (1 - 0.90)/0.94 = 0.10638

3. Compute the "new" posterior risk by multiplying the risk from triple marker screening (0.01) by the likelihood ratio (0.10638). Calculation: 0.01 x 0.10638 = .001638

4.. Divide 1 by the posterior probability to compute the "new" risk for trisomy 21.

Calculation: 1/0.001638 = 940

5. The new risk for trisomy 21 has changed from 1 in 100 to 1 in 940.