In order to help you understand what the results of prenatal cfDNA screening actually mean for you and your baby, we want to provide you more detailed information and some practical examples. Before doing so, we will first explain some basic (but often confusing) terms that are used in measuring how “good” a screening test is. This may be particularly helpful for those of you that may have received an abnormal prenatal cfDNA screening result.

Sensitivity (related to the false-negative rate)

Sensitivity measures the proportion of babies with a condition who are correctly identified as such.  For example, if 100 babies have the condition and the test detects 60 of the babies who have it, the sensitivity would be 60%.  40% of the babies who have the condition would not be picked up by the test and would therefore receive a false-negative result.

So, sensitivity essentially answers the question: “If my baby HAS Down syndrome what is the chance that prenatal cfDNA screening will be abnormal/high-risk?”.

For Down syndrome, most labs are quoting >99% sensitivity. This means that in higher-risk populations for which this test is recommended, if your baby has Down syndrome, there is over a 99% chance the results will come back “high-risk” or “abnormal”. When a lab says they have a 99% sensitivity, this does NOT necessarily mean that if you receive an abnormal result there is a 99% chance that your baby has the condition.

Specificity (related to the false-positive rate)

Specificity measures the proportion of babies WITHOUT a condition who are correctly identified as such.  For example, if you had 100 babies without the condition and 80 received a normal result, the specificity would be 80% and 20% of the babies would have a false positive result.

So, specificity essentially answers the question: “If my baby does NOT have Down syndrome, what is the chance that the prenatal cfDNA screening results will be normal/low-risk?”.

For Down syndrome, most labs are also quoting >99% specificity, meaning that if your baby indeed does NOT have Down syndrome, there is >99% chance that the prenatal cfDNA screening results will be normal/low-risk.

Positive Predictive Value (PPV)

PPV is calculated based on knowing the sensitivity, specificity and background risk of the condition. In this case, the background risk would be your specific age-related risk for Down syndrome, which increases as mom’s age increases or it may be your adjusted risk based on a previous traditional prenatal screening test)\.

Since the PPV is not intrinsic to the test, even with a very high sensitivity and specificity (>99%), the PPV can still be relatively low if the prevalence or background incidence of the condition is low.  The lower the background prevalence, the lower the PPV will be. Conversely, the higher the background prevalence of a condition, the higher the PPV will be. The PPV of a test may vary dramatically for age-related conditions such as Down syndrome depending on mom’s age. 

Some labs are quoting extremely high PPVs for Down syndrome and other conditions that may not be substantiated. Please see this blog for more information and talk to your provider about what a realistic PPV is given your age and background risk. 

PPV essentially answers the question: “If prenatal cfDNA screening is abnormal/high-risk, what is the chance that the baby actually has Down syndrome (given I have the same characteristics as the population, eg. same age, etc.)?”.

Negative Predictive Value (NPV)

NPV essentially answers the question: “If the prenatal cfDNA screening is normal/low-risk, what is the chance that the baby really does not have Down syndrome (given I have the same characteristics as the population, eg. same age, etc.)?”.

So, what is the most important thing to look at…Sensitivity? Specificity? PPV or NPV?

Well, they are all important and they are all somewhat related. However, whether or not your baby actually has the condition when you have received an abnormal result demands knowing the Positive Predictive Value (PPV) of the test for you (also can be referred to as the post-test probability when thinking of this on an individual level).

Again, PPV will answer the question: If the test is abnormal, what are the chances (in individuals with similar population characteristics such as age) that your baby actually HAS the condition?

Even though the sensitivity and specificity of the test may be >99%, the actual chance your baby is affected may only be 50%.

Prenatal cfDNA screening statistics and reporting are confusing, so be sure to ask your doctor or genetic counselor for clarification on any questions that you may have. And as a reminder, prenatal cfDNA screening results are not definitive. Amniocentesis or CVS is recommended to provide more detailed information if desired.