PPV Calculator for NIPT

“This is a video tutorial for healthcare providers of how to use the NIPT/ cell-free DNA screening predictive value calculator. My name is Erin Heckaman. I am a Licensed and Certified Genetic Counselor with Project Heritage. Project Heritage is a non-profit collaboration with Special Angels Adoption and The Center for Genomic Interpretation and funded in part through the Antioch Foundation. Project Heritage provides free services for women who have received a positive prenatal genetic test result. The link to the Project Heritage website is in the video description box below. https://clarifygenetics.org/projectheritage

This NIPT/ Cell free DNA screening predictive value calculator was created by the National Society of Genetic Counselors and the Perinatal Quality Foundation. These groups saw a need to create a resource to aid healthcare professionals in counseling their patients about the patients’ screening results. I will walk you through several case examples to see how different variables can affect the chance of the positive result being a true positive. The link to find this online calculator is in the video description box below.
https://www.perinatalquality.org/Vendors/NSGC/NIPT/

When you first open up the website, please read through the terms of use before continuing.

There is a wealth of information on this website beyond the actual calculator. If the terms, sensitivity, specificity, etc. are not very familiar or you just need a refresher, look through this tab on the website that provides definitions .

If you read through this, it discusses accuracy and how even a highly accurate screening test like NIPT can have a variable positive predictive value. Positive predictive value (PPV) represents the proportion of positive tests that are truly positive. Although test sensitivity and specificity are expected to remain the same across a broad population, the PPV of a test varies based on the prevalence of the condition in a given population. The rarer the condition, the lower the PPV when sensitivity and specificity remain unchanged.

In 2016, the American College of Medical Genetics issued guidelines to labs offering NIPT. In 2018 a team of collaborators evaluated the laboratories offering this testing and their findings were published in 2018 in Genetics and Medicine. There is a table with their findings that is updated regularly and I’ve linked it in the description box below. https://prenatalinformation.org/table/ One of their findings is that out of 10 major laboratories performing cell-free DNA prenatal testing, only one was reporting the Positive Predictive Value.

Let’s go through a case example. Negative predictive value is the chance that a negative result is a true negative. Here we take a case of Trisomy 21 maternal age at an estimated due date is 35. Here you have the sensitivity and specificity; these are the default performance metrics. If the laboratory you used provides their own sensitivity and specificity, please enter those in. We calculate it and the negative predictive value is greater than 99%. So the chance that this truly is a negative result is over 99%. Now we look at the positive predictive value for a patient who is 35 at her estimated due date, and she screens positive for Trisomy 21. If you read here it says the estimated prevalence of Trisomy 21 at 16 weeks gestation for women who are 35 is 1 in 296. The probability that her positive result on this screening test is a false positive is 21%. Please note that the prevalence is 1 in 296, but if there are findings on ultrasound, if there is a personal or family history that would impact prevalence, or if there are other factors, you can update the prevalence directly and not use the pre-populated estimate information.

If your patient had the sample drawn at a different week than 16 weeks gestation the prevalence will also be different. This is due to spontaneous loss in pregnancy. So if the patient is further along her likelihood, or the prevalence of Trisomy 21 would be lower. That is because of the risk like I said, of spontaneous loss which can happen.

If we look through another case, Trisomy 21 in a woman who is 25 years old the prevalence has decreased, and so the PPV we will see has also decreased. For a woman who was 35, the false positive was a 21% chance, and in a woman who is 25, this is a 49% chance it is a false positive.

Let’s look for Trisomy 18 in this patient who is 25. You can see the prevalence is even lower. So again the PPV will decrease in this condition with lower prevalence. The sensitivity and specificity has also changed with the default performance metrics. This patient, if they screen positive, it is an 85% chance that this is a false positive result.

Please remember that NIPT/ cell free DNA prenatal screening is just that – it is a screening test, and not diagnostic. Results from prenatal screening alone should not be used for making irreversible pregnancy decisions. Diagnostic testing, like an amniocentesis or CVS (chorionic villus sampling) is strongly recommended to confirm a prenatal screening test result.

Your words matter and the way you deliver the information from these test results matter. And conveying the correct information REALLY matters.

If you have a patient who has received a positive screening result from NIPT and are searching for more information and support for your patient, Project Heritage is here to help. Services are provided through Project Heritage at no-cost to the patient. The expert scientists at CGI do an in-depth look at the patient’s test result to review the accuracy of their report. Special Angels Adoption assists the patient with social work services and counseling, and offers a peer match program as well where patients can be matched up with someone who has had a similar prenatal diagnosis. Patients receive support no matter the outcome of the pregnancy.

If you would like to refer your patient to a genetic counselor, I’ve included a link in the description box below to aid you in your search in finding one. Genetic counselors can be found local to you or through telehealth, or you can reach out to the laboratory who performed the testing and they may have in-house genetic counselors to help explain and assist.
Please look through the links in the video description box below for helpful resources and remember that Project Heritage is here to help. Thank you.”