Cell-Free DNA Screening

SMFM Statement on Cell-Free DNA Screening

Cell-free DNA (cfDNA) screening has seen rapid uptake into clinical practice since introduction in 2011.  This screening modality has been largely recommended in patients at higher risk for aneuploidy, given more limited evidence regarding effectiveness in lower risk populations. A recent publication in the New England Journal of Medicine examined the use of cfDNA in an unselected population, including a large number of lower risk pregnancies. This study has increased the discussion surrounding the potential for use of cfDNA as a primary screening test in routine populations.  

SMFM has provided guidelines and consultation on use of cfDNA, including a joint Committee Opinion with the American College of Obstetricians and Gynecologists (ACOG), a rapid response statement following a high profile article in the Boston Globe, and a recent SMFM Consult Series document published in AJOG. The society will continue to evaluate the evidence surrounding use of this and other screening and diagnostic tests, as appropriate.  We continue to recommend the following as important points to consider regarding the use of cfDNA and other tests for aneuploidy:

• cfDNA screening appears to be the most accurate screening test for trisomy 21, which comprises about 50% of all chromosome abnormalities, and 8-10% of all significant birth defects.  Down syndrome is a relatively uncommon cause of intellectual disability in children born to young women.
• cfDNA does not screen for all chromosomal conditions. Rather, cfDNA very precisely targets the common aneuploidies and will not identify risk for the range of disorders potentially identified with traditional screening. 
• cfDNA is a screening test, and both false positive and false negative results occur.  This is particularly true in lower risk women, in whom a positive test is more likely to be a false positive.• Women who desire definitive information about chromosomal conditions in their pregnancy should be offered the option of amniocentesis or CVS.
• Diagnostic confirmation with CVS or amniocentesis is recommended for women with abnormal cfDNA results, particularly if clinical decision-making will change depending on the presence of aneuploidy. Irreversible decisions such as pregnancy termination should NOT be undertaken based solely on cfDNA results.
• A negative cfDNA result indicates a decreased risk and does not definitively rule out trisomy 21 or other chromosome conditions.
• Women with failed cfDNA tests are at increased risk for aneuploidy, and therefore need careful counseling about further testing, including the offer of diagnostic testing.
• Genetic counseling services are an important part in providing information in the care for patients.  Certified genetic counselors often play a role in provision of these important services.  The SMFM recommends payers provide adequate reimbursement for these services to provide ideal care for patients.
• All genetic screening is elective.  Whether a woman chooses to have aneuploidy screening, prenatal diagnostic testing, or no testing is a personal decision and any of these is a reasonable option.

The complexity of prenatal genetic testing emphasizes the importance of careful counseling regarding test preferences in pregnancy. Patients making decisions surrounding such testing must be provided accurate and complete information regarding the advantages and limitations of all testing options, including the option to decline prenatal genetic testing altogether. SMFM will continue to update guidance surrounding such tests as evidence emerges in the field.

For further information, please go to: https://www.smfm.org/publications/189-prenatal-aneuploidy-screening-using-cell-free-dna