Conventional prenatal screening methods are still the gold standard for most pregnant women despite the availability of cell-free DNA screening for aneuploidy, according to a consensus statement from the American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine.
The two organizations cited the limits of cell-free DNA screening performance and the limited data on cost effectiveness in the low-risk obstetric population for encouraging ob.gyns. to stick with conventional screening methods in the general obstetric population.
After cell-free DNA analysis became clinically available in 2011, ACOG and SMFM recommended it for women at increased risk of fetal aneuploidy, including women 35 years or older, fetuses with ultrasonographic findings indicative of an increased risk of aneuploidy, women with a history of trisomy-affected offspring, a parent carrying a balanced robertsonian translocation with an increased risk of trisomy 13 or trisomy 21, and women with positive first-trimester or second-trimester screening test results.
And in a 2012 joint committee opinion, ACOG and SMFM said that cell-free DNA testing should not be offered to low-risk women or women with multiple gestations because it hadn’t been sufficiently studied.
The updated committee opinion, outlines the pros and cons of using cell-free DNA screening in the general obstetric population.
“Patients should be counseled that cell-free DNA screening does not replace the precision obtained with diagnostic tests, such as chorionic villus sampling or amniocentesis, and therefore, is limited in its ability to identify all chromosome abnormalities,” the groups wrote in the updated opinion. “Not only can there be false-positive test results, but a positive cell-free DNA test result for aneuploidy does not determine if the trisomy is due to a translocation, which affects the risk of recurrence. If a fetal structural anomaly is identified on ultrasound examination, diagnostic testing should be offered rather than cell-free DNA screening.”
The sensitivity and specificity of the cell-free DNA screen in the general obstetric population are similar to those in high-risk patients. But the positive predictive value is lower in the general population because of the lower prevalence of aneuploidy. “That is, fewer women with a positive test result will actually have an affected fetus, and there will be more false-positive test results,” ACOG and SMFM wrote.
As a result, the revised opinion includes a recommendation specifying that management decisions, including the decision to terminate a pregnancy, should not be based on the results of cell-free DNA screening alone. Further diagnostic testing is now recommended for any patient who receives a positive result on cell-free DNA screening.
Similarly, women whose results are indeterminate, uninterpretable (“no call” result), or not reported at all should receive further genetic counseling and be offered comprehensive ultrasound evaluation and diagnostic testing. And women whose results are negative should be counseled that a negative cell-free DNA test does not ensure a normal pregnancy.
Additionally, most cell-free DNA testing identifies only trisomies 13, 18, and 21, which comprise a smaller proportion of the chromosomal anomalies found in the general obstetric population than among high-risk women. In one study cited in the opinion, up to 17% of clinically significant chromosomal abnormalities would not be detectable by most current cell-free DNA techniques.
The joint opinion now includes a recommendation against routinely using cell-free DNA screening for microdeletion syndromes. And it reminds physicians that cell-free DNA testing also doesn’t assess fetal anomalies such as neural tube defects or ventral wall defects, so patients who undergo cell-free DNA screening should still be offered maternal serum alpha-fetoprotein screening or ultrasound assessment. The latest opinion continues to recommend against the use of cell-free DNA testing for women with multiple gestations.