Cell-free DNA (cfDNA) screening, or noninvasive prenatal screening (NIPS or NIPT), takes advantage of fragments of placental DNA that circulate in the bloodstream.

cfDNA screening has a higher detection rate for trisomy 21 (Down syndrome), trisomy 18 (Edwards syndrome) and trisomy 13 (Patau syndrome) than other prenatal screening tests. Even if a patient is not interested in invasive diagnostic testing and its risks, cfDNA screening can provide information about the likelihood of several specific genetic conditions that might affect the baby. This can help patients prepare for a child with special needs or potentially change prenatal care.

However, cfDNA screening currently screens for only a few specific conditions. It is not a diagnostic test and is not a comprehensive test for all genetic disorders. For these reasons, cfDNA screening will be more appropriate for some patients than others. The interpretation of cfDNA results will also depend on the unique circumstances of each patient.

In these cases, you will practice:

• Weighing the benefits and limitations of testing for patients with different goals and concerns,
• Interpreting different cfDNA results, and
• Thinking ahead about the best next steps for patients with different indications and concerns.

Benefits and limitations

cfDNA screening is the most powerful screening tool available for Down syndrome (Trisomy 21), Trisomy 18 and Trisomy 13. It has advantages for some patients because it is noninvasive and does not involve a risk of miscarriage.

However, cfDNA screening is not diagnostic, and all patients should be informed of this limitation and the alternative of diagnostic testing. In the previous cases, you practiced considering testing strategy based on the indication, as well as the patient's motivations, expectations and attitudes toward uncertainty. 

cfDNA screening is not  the best choice for a patient when:

• The patient desires certainty about the presence of chromosome abnormalities
• The patient is concerned about less common chromosome abnormalities or single gene conditions
• Fetal structural anomalies are present

Because it is not a comprehensive genomic test, cfDNA screening should be used in conjunction with other screening tests, such as ultrasound and maternal serum AFP. 

Interpreting results

In the previous cases, you also practiced interpreting three possible results of cfDNA screening:

• Positive = Significantly increased risk for aneuploidy
• Negative = Significantly decreased risk for aneuploidy
• Test failure (no-call) = Insufficient or inconclusive

Interpretation of cfDNA screening results, along with counseling and follow-up decisions, will vary depending on several patient characteristics, including:

• Prior risk for aneuploidy (e.g., patient age, history, ultrasound findings, or serum screen results)
• Patient anxiety and tolerance for uncertainty
• Gestational dating
• Unique pregnancy characteristics (i.e., multiple gestation)
• The likelihood of other genetic and structural abnormalities

Tools are available to clarify risk and guide decision-making, including residual risk estimates provided by the lab and positive predictive value calculators. When in doubt about the best next steps, genetic professionals can facilitate interpretation, patient understanding and decision-making.

Visit Dig Deeper

For a more detailed discussion of:

• Testing methods
• Benefits and limitations
• Indications for screening 
• Confirmatory testing after a positive result
• Counseling about cfDNA screening