cfDNA are fragments of DNA that circulate in a pregnant person’s blood. Some of these fragments come from the pregnancy, and some from the pregnant person. In cfDNA screening, the fragments from the pregnancy are analyzed to find out whether the fetus has a low risk or high risk of having certain chromosome disorders.

cfDNA assesses the risk for several common chromosome disorders in which there are extra or missing chromosomes. This type of chromosome disorder is called aneuploidy.

Normally, there are 2 copies of each chromosome. 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. It also can screen for missing or extra copies of the X and Y sex chromosomes, if requested. 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 be performed beginning at 10 weeks of pregnancy.  

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

• A positive cfDNA screening test result means there is a higher chance that the fetus has a chromosome disorder compared with the general population.   

• A negative cfDNA screening test result means there is a lower chance that the fetus has a chromosome disorder compared with the general population.   

 The most accurate way to prenatally test for chromosome 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 the condition is requested. CVS is an option starting at 11 weeks of pregnancy, and amniocentesis is an option at 15 to 16 weeks of pregnancy. 

Sometimes, cfDNA screening will not be able to provide a test result. This can happen because there isn’t enough pregnancy-derived DNA available in the blood sample or because there is a problem interpreting the test result in the laboratory. The most common reasons are that the test was done before 10 weeks of pregnancy, increasing maternal weight, large fibroids, or because the fetus has a chromosome abnormality.  

Your healthcare professional may suggest additional testing based on your results and other risk factors.  

cfDNA is highly accurate in screening for Down syndrome and is slightly less accurate for trisomy 13 and 18. However, false-positive and false-negative results can occur. A false negative cfDNA screening result is a negative result when the fetus has the disorder being screened for. A false positive cfDNA screening result is a positive result when the fetus does not have the disorder being screened for.

Yes. A person’s age affects cfDNA screening’s positive predictive value (PPV). A test’s PPV is the likelihood that a person with a positive test result actually has the condition being tested for.   

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 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, ie, that the fetus has Down syndrome. There is a 5% chance that the result is a false positive.   

• 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.   

If you have a positive cfDNA screening result, it’s recommended that you meet with a maternal-fetal medicine subspecialist, geneticist, or genetic counselor to review your results and discuss follow-up testing options. Patients with positive results are usually offered an ultrasound evaluation and diagnostic testing.

cfDNA screening does not screen for genetic disorders caused by changes in a single gene. Although some companies offer testing for additional chromosome disorders, such as trisomy 16 and trisomy 22, there is not much information about the accuracy of these tests. For this reason, cfDNA screening for genetic conditions other than the common trisomies is not recommended.   

It is important to know that cfDNA screening doesn’t screen for structural birth defects. All pregnant people are offered a second-trimester ultrasound exam to check for these types of disorders.    

cfDNA screening is less accurate in people pregnant with twins if one twin stops developing early in the pregnancy. No information is available on the test’s accuracy in people carrying three or more fetuses. cfDNA screening can also be less accurate in patients with a history of a transplanted organ.