A newer, non-invasive test that analyzes fetal DNA circulating in a pregnant woman’s blood is proving more accurate in screening for trisomy 21 (Down syndrome) and other chromosomal abnormalities than the standard two-part sequential screen or maternal serum quad screen.
With a simple blood draw from an expectant mother, the cell-free fetal DNA test (cf DNA) provides higher sensitivity and specificity as well as a significantly lower false-positive rate than traditional testing. In fact, according to a joint committee opinion issued by the American Congress of Obstetricians and Gynecologists (ACOG) and the Society for Maternal-Fetal Medicine, several large-scale validation studies have demonstrated detection rates for fetal trisomy 13 (Pa-tau syndrome), trisomy 18 (Edwards syndrome), and trisomy 21 of greater than 98 percent with very low false-positive rates (less than 0.5 percent compared to 3.5 percent for the sequential screen and 5 percent for the quad screen).
These findings led the committee to conclude that cell-free fetal DNA appears to be the most effective screening test for aneuploidy in high-risk women, leading a growing number of insurers to cover the test in these cases. It is not currently recommended for routine screening in low-risk women due to a lack of long-term outcome and cost-effectiveness data in this population.
“The high-risk population is defined as women who meet one or more of these criteria,” explains Cooper OB/GYN faculty member Tuan A. Dinh, MD. “They are 35 and older at delivery, have had a prior pregnancy with a chromosomal abnormality, their fetal ultrasound findings indicate an increased risk of trisomy, or they have had a sequential or quad screen that is positive for trisomy.”
Dr. Dinh and colleague Meena Khandelwa l, MD, agree that the cf DNA test offers numerous other advantages over existing technology. “It’s a single, simple, non- invasive test that can be per- formed as early as 10 weeks into a pregnancy,” says Dr. Khandelwal, noting that the sequential screen requires two patient visits and final results may not be available for 16 or 17 weeks into the pregnancy. The cf DNA test also can re- veal the fetus’ gender.
Further, she notes, some of the cf DNA tests now avail- able can, through deletion assays, also detect anomalies of the sex chromosomes such as Turner’s syndrome (XOsyndrome), Klinefelter’s syndrome (XXY syndrome), Triple X syndrome (XXX syndrome).
Drs. Khandelwal and Dinh stress, however, that cf DNA remains a screening test, and that additional, more invasive diagnostic testing – such as amniocentesis or chorionic villus sampling (CVS)–must be done before taking action to terminate a pregnancy.
“Because cf DNA testing is done only for high-risk women, here at Cooper we always recommend they undergo genetic counseling to understand their options as well as what this test can and cannot screen for,” Dr. Khandelwal says. “Patients must understand the whole picture before choosing this test, and they must be counseled well – something that general obstetrician-gynecologists may not have the time or training to do. “This test holds a lot of promise,” she adds. “Companies are competing to improve and refine the technology, and that’s a good thing. We’ll be able to test even more chromosomal abnormalities using tiny pieces of DNA. And the price of testing will come down. I believe it will eventually become the screening test for most women in the future.”