Expert Commentary
When is cell-free DNA best used as a primary screen?
At age 38 years, cell-free DNA screening as the first-line test becomes the optimal strategy; at age 40 years, cell-free DNA as a primary screen...
What are the advantages of cfDNA screening for low-risk patients?
There are several benefits of cfDNA screening versus traditional screening or diagnostic testing, which are the other options available ( TABLE 2 ). For Down syndrome, the detection rate is higher and the false-positive rate is lower than that seen with traditional aneuploidy screening using serum analytes and nuchal translucency ultrasonography. 1,2
TABLE 2 Pros and cons of cfDNA screening in low-risk patients
Pros
- High detection rate and very low false-positive rate
- Can be performed any time after 10 weeks’ gestation
- Requires a single blood test at any gestational age
- Results presented in simple “Yes” or “No” format
- As with other screening tests, cfDNA provides a noninvasive determination of risk
Cons
- Tests for a limited range of conditions, which are rare in low-risk patients
- Is not as comprehensive or definitive as diagnostic testing with amniocentesis or chorionic villus sampling
- Results do not adjust for patient’s prior risk
- Positive results require calculation and interpretation of positive predictive value by provider
- Low fetal DNA and other factors can lead to test failure in some cases
- Cannot be used with vanishing twin
- Can reveal unsuspected maternal conditions of uncertain significance
The test can be done any time after 10 weeks’ gestation without the narrow gestational-age windows required or the need for accurate gestational age determination using traditional screening to accurately interpret results. cfDNA screening involves a single blood test that does not require integration with multiple serum markers or ultrasound findings. Finally, results are generally presented in a simple “Yes” or “No” format that is easy for providers and patients to understand.
CASE Continued
Your patient’s results are positive for trisomy 13. Her understanding is that the test is more than 99% accurate, and she interprets this to mean that the chance of trisomy 13 in her fetus is more than 99%. She is distraught and asks about pregnancy termination.
What are the limitations of cfDNA screening?
Similar to other noninvasive screening tests, cfDNA screening does not carry direct risk to the pregnancy. However, there are limitations to this testing. As a result, the American College of Obstetricians and Gynecologists (ACOG) and the Society for Maternal-Fetal Medicine (SMFM) recently have stated that traditional screening is the most appropriate option for most women. 11,12
One reason that cfDNA screening may not be the best choice for low-risk women is that Down syndrome is quite uncommon in this group, so cfDNA screening is a very precise test for a rare condition. Traditional multiple marker screening, on the other hand, is more effective at signaling risk for the broad range of adverse perinatal outcomes that can affect a pregnancy, including other structural birth defects, as well as such obstetric complications as preterm birth, preeclampsia, and fetal growth restriction. 13,14
Many women who undergo cfDNA screening are under the impression that they have had a definitive test for all birth defects when, in fact, the coverage of cfDNA for all possible birth defects in a low-risk woman is very limited; her residual risk for a birth defect is little changed by a normal cfDNA result.
