This is a question that gets asked at least once a week in a comment to one of the hundreds of posts on this blog: my blood test just came back for Down syndrome–what does it mean? Fortunately, there’s an on-line tool to help understand these results.
Usually, the comment continues along these lines:
I’m [this many] years old. I took the [MaterniT21, Harmony, Panorama, etc.] test. Today, my OB called saying the results were positive. I asked what that meant, and she said I had a 99% chance of having a baby with Down syndrome. Is this correct? Please help.
After explaining that cell-free DNA screens like Sequenom’s MaterniT21 or Illumina’s verifi are never positive, and linking to this post on why saying those results are “99% accurate” amounts to malpractice, I then would link to the National Society for Genetic Counselors (NSGC) fact sheet on cfDNA screening.
That fact sheet explains why the critical number is not the claimed “99%” but what the screen result’s positive predictive value (PPV) is. This was a concerned raised in 2013 with the way cfDNA screen results were being reported and leading to much confusion on what a screen-positive meant for the actual probability that the pregnancy was positive for Down syndrome. This is what PPV relays.
Then, I’d link the commenter to this post for the simple chart in the middle that shows the PPV associated with the age of the expectant mother, with the PPV rising with the age, just as the chance for having a child with Down syndrome increases with the age of the mother.
But those figures were based on my own calculations, and, being a lawyer by training, the joke is that lawyers go to law school because there’s no math.
Fortunately, there is now an online tool that provides more precise calculations to determine a cfDNA screen results PPV.
The Perinatal Quality Foundation created a PPV calculator.
The default setting is if you are an expectant mom who had cfDNA screening as an initial screen, then you enter your age and the condition the screen reported detecting. After entering this information, then you can enter the sensitivity and specificity of the cfDNA laboratory (or simply use the default settings for a close approximation). Then, by pressing “Calculate” you will receive your PPV based on a screen-positive cfDNA screen.
The other method is to enter your prevalence, if you had a previous conventional screen, such as nuchal translucency combined or the Quad test. Then, you can enter the lab’s sensitivity and specificity information and press “Calculate” to receive your PPV.
The same calculator also provides the negative predictive value (NPV) for your screen results. The NPV can tell you the probability that you are not having a child with Down syndrome.
Since this tool became available, it is the one I most often use in answering expectant mother’s question of “what does my cfDNA screen result mean?” You can, too, simply by accessing the Perinatal Quality Foundation’s helpful PPV/NPV calculator at this link.
Lastly, professional guidelines recommend that patients receive written informational resources about the tested-for condition when receiving a screen-positive result. The professionally recommended resources for Down syndrome can be found at the Prenatal Resources Tab on this site.