NEW ORLEANS – Noninvasive prenatal testing using cell-free fetal DNA found in the maternal bloodstream detects more than 80% of the most common trisomies, including the one for Down syndrome, according to results presented at the annual Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine.
Expectant mothers and their treating physicians now may have a wider range of options for balancing the risks inherent in the more invasive kinds of diagnostic testing, such as chorionic villus sampling and amniocentesis, against the desire for such tests’ near-perfect diagnostic accuracy, according to Dr. Mary Norton.
"Some of the other screening tests that we use, some of the ultrasound screens and some blood tests, have a number of false positives," the study’s presenter, Dr. Norton, vice chair of clinical and translational genetics at the University of California, San Francisco, said in an interview.
For the majority of women, the screening tests show no fetal abnormalities, but the experience can unnerve some women, who find that the test just isn’t worth the risk, said Dr. Norton. Current recommendations from the American College of Obstetricians and Gynecologists (ACOG) are that noninvasive prenatal testing (NIPT) only be offered to high-risk pregnant women as an alternative to invasive testing if integrated ultrasound/blood test screens come back positive.
While diagnostic invasive testing offers "near 100% accuracy," there is a 1 in 500 chance the woman will miscarry after having such a procedure, Dr. Norton said. NIPT, which was introduced into clinical practice in 2011, relies on a simple blood test and is typically performed during the second trimester.
"For a woman who is losing sleep with worry that her fetus may have a chromosome problem, having a test like an amniocentesis that comes back normal may allow her to enjoy the rest of her pregnancy," said Dr. Norton. "For someone whose goal is to avoid diagnostic testing at all costs, to avoid the fear of having a false positive, [NIPT] may be better to detect fewer things but to avoid false positives."
Using the California Prenatal Screening Program database from March 2009 through December 2012, Dr. Norton and her colleagues reviewed all karyotype results from invasive diagnostic tests of singleton pregnancies performed after a prenatal screen indicated possible abnormalities. In all, 26,059 results were analyzed and divided according to either the abnormalities that NIPT is currently able to detect, including nonmosaic trisomies 13, 18, and 21 and sex-chromosomal aneuploidy; or abnormalities currently undetectable by NIPT, such as mosaicism.
During the study period, more than 1.3 million women were screened, with just over 5% (68,990) screening positive for trisomy 18 or 21. Of screen-positive women, nearly 38% (26,059) assented to an invasive prenatal test; of these, 12% (2,993) came back with abnormal results. Just more than 83% (2,488) of those abnormalities were ones detectable by NIPT, while just less than 17% (511) were not. The most common abnormal result, at 53% (1,592), was trisomy 21 (Down syndrome), which has been shown to comprise more than half of all abnormalities detected prenatally.
Women aged 35-39 years composed more than a third of all women studied. While in women under age 30, NIPT misses about 22% of aneuploidies, Dr. Norton said in her presentation that in women over age 45, that number drops dramatically to 8%, largely because of the correlative risk for trisomy 18 and 21 and advanced maternal age.
She noted that one of the limitations of the study was the fact that it included only screen-positive women, and thus the study group was "enriched" for trisomy 21; hence, the results cannot be generalized to the unscreened population, which has a different rate and spectrum of fetal abnormalities.
"Our calculations are for potential detection by NIPT for the target disorders. While the sensitivity is high, it is not 100%; therefore, the overall detection for all chromosomal abnormalities will be less than the 83% we report," Dr. Norton told the audience. "In addition, only 38% of screen-positive women chose to have invasive testing, and those declining such testing might have had different risks, and therefore different outcomes."