Positive cfDNA Screen: Step-by-Step Guide (while waiting to meet with your doctor)

You might have recently received a call from a nurse or genetic counselor, perhaps someone you've interacted with before, or perhaps not. Alternatively, you may have logged into your patient profile and come across a test result indicating something like "increased risk," "positive," or "high likelihood."

The outcome might have taken you entirely by surprise, and you might be pondering what steps to take next. It's crucial to note that this blog post serves as a bridge between receiving the initial result and having a conversation with your doctor, and not as a substitute for medical advice.

What’s the first step?

A good starting point is acknowledging your emotions and ensuring you give yourself the necessary space. Some individuals may require time away from information to process everything, while others might feel ready to move forward immediately. Arm yourself with your coping strategies. You might consider sharing the news with your partner or close friends/family to surround yourself with your support system.

In tandem with the above step, it's important to understand that the result indicates an increased chance for the pregnancy to have the condition, but it cannot definitively diagnose it. While it can still feel alarming to receive the result, it is not conclusive. More testing is needed to know for certain if the pregnancy has the condition listed.

Next, let’s discuss the details of the test and what it all means.

Cell-free DNA screening (cfDNA) can be called non-invasive prenatal testing (NIPT) or non-invasive prenatal screening (NIPS). There are many labs that offer this type of testing.


Cell-free DNA screening is performed after 10 weeks of pregnancy. It assesses the chance for Down syndrome, Trisomy 18, Trisomy 13, and sex chromosomal conditions like Turner syndrome or Klinefelter syndrome. It can also assess the chance for some microdeletions which are small pieces of the chromosome that could be missing. If a small piece of the chromosome is missing, then that means 5-10 genes are missing which can cause certain features or symptoms.  

Cell-free DNA screening is performed by a blood draw. The amount of DNA is the bloodstream is analyzed. In the bloodstream during pregnancy, there is DNA from the pregnant person and DNA coming from the placenta. It is normal to have DNA from the placenta in the bloodstream.

The lab performing cell-free DNA screening is able to determine which chromosome the DNA is coming from as well as if there is the correct amount of DNA for each chromosome. There should be a certain amount of DNA from each chromosome found in the bloodstream. If there appears to be more or less of the DNA from a certain chromosome, then there may be an extra or missing chromosome. If the lab suspects an extra or missing chromosome, then the result is positive. Chromosomal conditions are caused by having too much or too little DNA. A positive result means the chance the pregnancy has a chromosomal condition is increased.

If cell-free DNA screening comes back positive for a chromosomal condition, then a certain value needs to be considered. This value is called the positive predictive value or PPV. The PPV is the lab’s confidence that the positive result is truly a positive result. For example, if the test is positive for Down syndrome and has a PPV of 60%, then the chance this result is a true positive result is 60%.

Most reports have the PPV listed on the first page of the report. You can use this number to help better understand the chance the result is truly positive. Even if the PPV is 99%, it still does not absolutely mean that the pregnancy has the condition. Confirmation testing is still needed.

Why is confirmation testing still needed?

A screening test can be a false positive. The technology used to assess the DNA does not look at the chromosomes directly. Instead it uses algorithms to determine the amount of DNA. The technology is called next generation sequencing. The confirmation testing used is called “karyotype” or “microarray” analysis. These tests can more accurately count the number of chromosomes compared to the next generation sequencing technology.

Most importantly, the DNA that has been assessed is DNA coming from the placenta, not from the baby. While the DNA of the placenta and baby most often are the same, there are times they differ. This means that in some cases, the placenta may have an extra chromosome, but the baby has the typical number of chromosomes and does not have a chromosomal condition. When this happens, it is called placental mosaicism. Therefore, the test may be picking up only what is going on for the placenta but not for the baby.

What confirmation testing is available?

The confirmation testing available will depend on what gestational age you are and if you are comfortable pursuing a procedure. There is the option to test while you are pregnant or to wait until after the baby is born.

• Chorionic Villus Sampling (CVS)

  • CVS is a procedure performed after the 10th week of pregnancy until 13 weeks and 6 days. A biopsy of the placenta, specifically the chorionic villi, is sent to a lab to be tested for chromosomal conditions. The placental biopsy can be obtained either through the cervix or through the abdomen. Ultrasound guidance is used throughout the procedure. There is risk for miscarriage, bleeding, infection, etc. Some studies quote a 1 in 100 risk for a complication, yet it is important to ask the physician performing this procedure what he or she personally quotes.

• Amniocentesis

  • Amniocentesis is a procedure performed after the 16th week of pregnancy. Amniotic fluid is obtained with a long, thin needle entering through the abdomen into the amniotic sac. Ultrasound guidance is used throughout the procedure to get a pocket of fluid away from the baby. The fluid is sent to a lab to be tested for chromosomal conditions. There is risk for miscarriage, bleeding, infection, etc. Some studies quote a 1 in 500 to 1 in 1000 risk for a complication, yet again, ask the physician performing this procedure what he or she personally quotes.

Given these procedures have a risk for complication, not everyone decides to complete confirmation testing while still pregnant. Other people feel like that while there is a risk, receiving confirmatory results while still pregnant is important to them. They may use the results to gain reassurance that the baby doesn’t have the condition or if the condition is confirmed, then they use that information to prepare for their baby, consider adoption, or termination of pregnancy.

Where can I learn more about the condition?

Down Syndrome/Trisomy 21

Every state, and sometimes cities, will have a Down Syndrome Network or Association for support. DownSyndromePregnancy.org is a great resource as well as the American Academy of Pediatrics.

Sex Chromosomal Differences

Triple X syndrome, Klinefelter syndrome, XYY syndrome, and other variations of sex chromosome differences can now be screened for with cfDNA screening. The AXYS Association is a great network of support and resources. Living with XXY is another helpful organization for Klinefelter syndrome.

Turner Syndrome

Turner syndrome is when there is one X chromosome as opposed to two. It is considered a sex chromosomal difference. The Turner Syndrome Society provides excellent resources.

Trisomy 13 and Trisomy 18

Often Trisomy 13 and Trisomy 18 are discussed together; however, the conditions are substantially different in their features and life expectancy. Trisomy.org is an excellent resource and makes available factual pamphlets for individuals to learn more about each condition.

What do I do if the confirmation testing confirms the diagnosis?

How you use the confirmation test results is highly personal. Your healthcare provider can discuss your options with you in more detail. You’ll want to make sure you are given information about the condition. Your provider can help discuss what treatment and/or surgeries are possible. They can connect you with other healthcare providers, who would administer that treatment, as well as families who have also received a prenatal diagnosis. Some individuals may pursue parenthood, adoption, or termination of the pregnancy. Resources to check out at any time include: Ending a Wanted Pregnancy and Carrying to Term. These resources may not be applicable to everyone, and your provider can help point you to resources that may be more helpful to you depending on the diagnosis and your situation.

* This blog constitutes general information about genetic testing and medical screening. This blog does not offer or provide medical advice or diagnosis, and nothing in this blog should be construed as medical advice or diagnosis. Do not rely on the information in this blog/article to make medical management decisions. Please consult with a medical professional before making those decisions. Do not delay in seeking professional medical advice if you think you have a medical concern. Do not disregard professional medical advice based on any information received in this blog.