Cell-free DNA (cfDNA) refers to tiny fragments of DNA that are found in a pregnant person’s bloodstream. Some of these DNA fragments come from the pregnant person, and some come from the placenta, which can reflect the fetus’s genetic makeup. 

In cfDNA screening, these DNA fragments are analyzed to find out whether the fetus has a low risk or high risk of having certain chromosome disorders.  

cfDNA helps identify the risk of several common chromosome disorders where there are extra or missing chromosomes. This type of chromosome disorder is called aneuploidy.   

Normally, there are 2 copies of each chromosome (one is inherited from each parent). In Down syndrome, also called trisomy 21, there is an extra copy of chromosome 21. cfDNA checks for trisomy 21 as well as trisomy 13 and trisomy 18. Most of the time, these disorders are not inherited from the parents but rather occur by chance. The chances of having a child with trisomy 13, 18, and 21 increase with maternal age. 

cfDNA screening can also look for missing or extra copies of the sex chromosomes. Sex chromosomes determine the genetic sex of a fetus (typically XX for female and XY for male). This part of cfDNA screening is optional.  

cfDNA screening can be performed beginning at 9 to 10 weeks of pregnancy. Some people choose to have cfDNA screening as early in the pregnancy as possible. cfDNA screening can also be done later in pregnancy if an ultrasound exam shows a concern or other issues arise.   

cfDNA is a screening test. It cannot tell for certain whether the fetus has a chromosome disorder. It only reports the chances that a fetus is affected: 

• A positive cfDNA screening test result means there is a high chance that the fetus has a chromosome disorder.   

• A negative cfDNA screening test result means there is a low chance that the fetus has a chromosome disorder.   

The most accurate way to test for aneuploidy and other genetic conditions is with a diagnostic test, such as chorionic villus sampling (CVS) or amniocentesis. A diagnostic test can tell with certainty whether the fetus has a chromosome disorder. It can also diagnose other genetic disorders like cystic fibrosis and sickle cell disease if specific genetic testing for these conditions is requested.  

CVS is an option starting at 11 weeks of pregnancy, and amniocentesis is an option starting at 15 to 16 weeks of pregnancy. Both have a very low risk of pregnancy loss of less than 0.5%.   

Diagnostic testing is an option for all pregnant people, regardless of their age or risk factors.   

cfDNA screening is an option for any pregnant person who wants more information on their risks of having a child with the most common chromosomal conditions. It’s often chosen by people who:  

• Want to know more about their pregnancy  

• Are over age 35 

• Have had abnormal ultrasound findings  

• Have a personal or family history of genetic conditions 

Yes. Maternal serum screening is a blood test that measures certain substances in the mother’s blood. Test results can be combined with ultrasound results. cfDNA is the most accurate screening test currently available for trisomy 13, 18, and 21. However, no screening test is as accurate as a diagnostic test.  

In some cases, cfDNA screening may not provide a result. This is called a “no-call” or test failure. It may happen if: 

• The test was done too early (before 10 weeks) 

• There wasn’t enough pregnancy DNA in the blood sample 

• There are large fibroids or a higher body weight 

• The fetus has a chromosome condition 

If this happens, your healthcare professional may suggest: 

• Repeating the cfDNA test 

• Using a different cfDNA test 

• Going directly to diagnostic testing 

Any pregnant person can request diagnostic testing, which will provide the most definitive information about your pregnancy.  

cfDNA is highly accurate in screening for Down syndrome and is slightly less accurate for trisomy 13 and 18.  

Screening for sex chromosome conditions is less accurate than screening for trisomies 13, 18, and 21. Results can be harder to interpret and may lead to additional testing. Before deciding to have sex chromosome screening, talk with your healthcare professional about what the results could mean and whether this part of the test makes sense for you. 

Screening test results can sometimes be wrong. With any screening test, there is a chance of:  

• A false-positive result ( the test shows a higher risk, but the fetus does not have the disorder)  

• A false-negative result (the test shows a lower risk, but the fetus does have the disorder)  

Yes. A person’s age affects cfDNA screening’s positive predictive value (PPV). A test’s PPV is the likelihood that a pregnant person with a positive test result actually has a fetus with the condition being tested for.  Thus, the pregnant person’s age itself does not impact the way the blood test is run, but, rather, the likelihood of disease in a high-risk result.  

PPV varies based on how common the condition is in a certain group of people at a given time. The rarer the condition, the lower the PPV.   

Because the risk of having a child with trisomy 13, 18, or 21 increases with the age of the pregnant person, the cfDNA screening PPV for these conditions differs by age. For example:  

• A 40-year-old pregnant person has a higher risk of having a baby with Down syndrome (1 in 50). The PPV is higher in this group of people.   

• A 20-year-old pregnant person has a lower risk (about 1 in 800). The PPV is lower in this group of people.  

Let’s say that both pregnant persons have cfDNA screening at 10 weeks of pregnancy and receive a positive result for Down syndrome.   

• For the 40-year-old pregnant person, the PPV is 95%. This means there is a 95% chance that the positive result is a true positive (in other words, the fetus has Down syndrome). There is a 5% chance that the result is a false positive (the result is wrong).   

• For the 20-year-old pregnant person, the PPV is 55%, meaning there is a 55% chance that the positive result is a true positive and a 45% chance the result is a false positive.     

PPV may be reported with some cfDNA screening results. If it is not, a healthcare professional or genetic counselor will be able to calculate the PPV.