Understanding statistics can be challenging. Unfortunately, familiarity with some statistics are necessary to help you understand your genetic test results.
One statistical term that is important in prenatal genetics, particularly with cfDNA, is positive predictive value (PPV). PPV answers the question:
If my test comes back ‘high-risk’ or ‘abnormal’, what are the chances that someone in my exact position (same age, background risk, etc.) will have a baby with the condition that I tested positive for?
In other words, what are the chances that my positive test result is a true or actual positive?
The equation that is used to calculate PPV is:
Sensitivity X Prevalence / [Sensitivity X Prevalence + (1 – Specificity)(1 – Prevalence)]
To put this all in practice, let’s calculate the PPVs for our 25-, 30-, and 35-year-old patients above for their cfDNA testing. Most cfDNA testing labs report that they have an approximate 99.9% sensitivity and specificity.
Sensitivity (0.999) X Prevalence (1/1041 = 0.00096061) / Sensitivity (0.999) X Prevalence (0.00096061) + [1 – Specificity (0.999)][1 – Prevalence (0.00096061)]
So, we’re left with:
0.999 X 0.00096061 / 0.999 X 0.00096061 + (1 – 0.999)(1 – 0.00096061)
0.999 X 0.00096061 / 0.999 X 0.00096061 + (0.001)(0.99903939)
0.999 X 0.00096061 / 0.999 X 0.00096061 + 0.00099904
0.999 X 0.00096061 / 0.00095965 + 0.0009904
0.00095965 / 0.00095965 + 0.0009904
0.00095965 / 0.00195005
0.492
So, if a 25-year-old woman has a ‘positive’ or ‘high-risk’ cfDNA result for Down syndrome, there’s only a 49.2% chance that her pregnancy actually has Down syndrome.
(0.999) X (1/701 = 0.00142653) / (0.999) X (0.00142653) + (1 – 0.999)(1 – 0.00142653)
0.999 X 0.00142653 / 0.999 X 0.00142653 + (0.001)(0.99857347)
0.999 X 0.00142653 / 0.999 X 0.00142653 + 0.00099857
0.999 X 0.00142653 / 0.0014251 + 0.00099857
0.0014251 / 0.0014251 + 0.00099857
0.0014251 / 0.00242367
0.588
So, if a 30-year-old woman has a ‘positive’ or ‘high-risk’ cfDNA result for Down syndrome, there’s only a 58.8% chance that her pregnancy actually has Down syndrome.
(0.999) X (1/297 = 0.003367) / (0.999) X (0.003367) + (1 – 0.999)(1 – 0.003367)
0.999 X 0.003367 / 0.999 X 0.003367 + (0.001)(0.996633)
0.999 X 0.003367 / 0.999 X 0.003367 + 0.000996633
0.999 X 0.003367 / 0.003363633 + 0.000996633
0.003363633 / 0.003363633 + 0.000996633
0.003363633 / 0.004360266
0.771
So, if a 35-year-old woman has a ‘positive’ or ‘high-risk’ cfDNA result for Down syndrome, there’s only a 77.1% chance that her pregnancy actually has Down syndrome.
***These are just examples using hypothetical sensitivities and specificities.
As these calculations show, as the chance (prevalence) of the condition increases along with mom’s age, the PPV also increases. The more rare the condition is, the lower the PPV likely is (despite very high sensitivity and sensitivity).
Many labs do not provide a PPV calculation, but your genetic counselor or other provider should be able to help you calculate the PPV.