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cfDNA screening should not be performed in the general obstetric population, according to this Opinion.
Conventional prenatal screening methods remain the most appropriate first-line screening choice for most women in the general obstetric population, according to updated recommendations on cell-free DNA (cfDNA) screening for fetal aneuploidy issued by The American College of Obstetricians and Gynecologists Committee on Genetics jointly with the Society for Maternal-Fetal Medicine.
The Committee Opinion (Number 640) was released online in June 2015 and subsequently published in the September 2015 issue of Obstetrics and Gynecology.
The primary motivation for undertaking the update was to review the role of cfDNA screening for all pregnant women, recognizing the increase in data on this topic since the original Committee Opinion (Number 545) was published in December 2012.
The revised document also newly provides recommendations for follow-up of women who have a “no call” result from a cfDNA screening test, stating that they should receive further genetic counseling and be offered comprehensive ultrasound evaluation and diagnostic testing because of an increased risk of aneuploidy.
As another key recommendation, the Committee reaffirmed its original opinion that there is insufficient evidence to support use of cfDNA screening in women with multiple gestations.
Joseph R Biggio, Jr, MD, Chair of the Committee on Genetics and Professor and Director of the Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Alabama at Birmingham School of Medicine, told Contemporary OB/GYN, “The uptake of cfDNA screening into clinical practice has occurred much more quickly than anything else we have seen in obstetric medicine. The original Committee Opinion focused on use of this technology in high-risk women because they were the subjects included in the available studies that validated cfDNA testing. Since then, more studies came out providing data on the performance of this technology in lower-risk women who are seen in a general obstetric population.”
“While the latter studies showed cfDNA testing performs similarly in terms of its sensitivity and specificity in the low-risk and higher-risk groups, the test has a lower positive predictive value (PPV) among women in the general obstetric population, given their lower prevalence of fetal chromosomal abnormalities. Considering the lower PPV and our feeling that there was still enough unknown about how to most cost-effectively utilize cfDNA testing in the general obstetric population, we could not recommend its routine use in this group for screening at this time,” he said.
Dr Biggio also pointed out that the Committee Opinion highlights inter-laboratory differences in the reporting of cfDNA results and encourages laboratories to transition away from providing either a binary type result (positive or negative) or a percentage estimation of aneuploidy risk (eg, >99% chance) to reporting PPV (the chance that the test is truly positive) or residual risk (the chance that a negative test result is false).
“Clinicians should not misinterpret percentage chance of aneuploidy as a positive predictive value. The latter information is much more transparent and accurate and, therefore, enables patient counseling and informed decision making,” he said.
“Bringing the issue of PPV into focus also further emphasizes the recommendation that irrevocable decisions should not be made based only on the cfDNA result.”
The recommendations about follow-up for women with a “no call” result are based on studies showing aneuploidy rates of up to 25% among women with such a result. Further, the Committee Opinion states, “Although repeat screening can be performed, it may delay the diagnosis of aneuploidy, potentially limiting reproductive options, and only 50% to 60% of repeat screens will provide a result.”
Dr Biggio said, “This is important information for providers to be aware of. They need to understand that in the situation where the cfDNA result comes back as not reported, indeterminate, or uninterpretable, they should not just repeat the screen multiple times or ignore the result.”