Down Syndrome and Other Trisomies Reliably Detected With Noninvasive Blood Test

Down Syndrome and Other Trisomies Reliably Detected With Noninvasive Blood Test

A noninvasive test that analyzes fetal cell-free (cf) DNA in a pregnant woman’s blood can accurately detect trisomy 21 and other genetic fetal abnormalities in the first trimester, according to the results of a new study.1
Chorionic villus sampling (CVS) and amniocentesis are the only tests that can definitively diagnose genetic abnormalities in a fetus, but these invasive tests are associated with a risk of miscarriage. A combined screening test, usually conducted between 11 and 13 weeks’ gestation, that involves maternal serum biochemistry and an ultrasound scan is the current standard of screening for fetal aneuploidies. However, it has recently been demonstrated that the cfDNA test performs well not only in high-risk populations but also in general populations when used as a high-performance screening test in the first trimester.2
This newest study, which included 1005 women with a singleton pregnancy, was the first to demonstrate the feasibility of routine screening for trisomies 21, 18, and 13 by cfDNA testing at 10 weeks’ gestation.1 Because of various problems with the blood samples or delays in transporting them to the testing facility, results of cfDNA testing were available for 984 women. For this study, risk scores of less than 0.01% were considered “very low,” and risk scores of greater than 99% were considered “very high.”
Most women (n=967) were at very low risk for trisomies 21, 18, and 13. For 11 women, the risk was very high for trisomy 21 but very low for trisomies 18 and 13. Five women had a very high risk for trisomy 18 but a very low risk for trisomies 21 and 13. Only 1 woman had a risk score of 34% for trisomy 13, with very low risk for trisomies 21 and 18.
Of the 17 women designated high risk for a fetal aneuploidy, 16 underwent CVS testing. One woman had a miscarriage before undergoing CVS. The results of CVS testing confirmed a fetal aneuploidy in 15 of the 16 cases. In 1 case, molecular and cytogenetic analyses revealed a normal karyotype that had been deemed high risk for trisomy 18.
The main advantage of cfDNA testing compared with the combined test is the substantial reduction in false-positive test results (0.1% for cfDNA testing vs 3.4% for the combined test). Another advantage of cfDNA testing is that the results are reported in a way that makes it easier for parents to decide whether to seek confirmation through more invasive testing.

Pertinent Points:
- Routine screening for trisomies through detection of fetal cell-free (cf) DNA in maternal blood at 10 weeks is feasible.
- The advantages of cfDNA testing, compared with combined testing, are a significant reduction in the rates of false-positive test results and the ability to report risk as very high (> 99%) or very low (< 0.01%).
- Disadvantages to cfDNA testing are the inability to provide results in all test samples and the need to confirm abnormal results through invasive tests.


1. Gil MM, Quezada MS, Bregant B, et al. Implementation of maternal blood cell-free DNA testing in early screening for aneuploidies. Ultrasound Obstet Gynecol. 2013. DOI: 10.1002/uog.12504.
2. Nicolaides KH, Syngelaki A, Ashoor G, et al. Noninvasive prenatal testing for fetal trisomies in a routinely screened first-trimester population. Am J Obstet Gynecol. 2012;207:374.e1-6.
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