Detecting Down Syndrome
During pregnancy, maternal blood flows against the placenta, allowing the exchange of nutrients, blood gases, and cellular and genetic material. Simultaneously, placental cells are being shed into the maternal circulation, resulting in small fragments of fetal DNA circulating in the maternal blood and accounting for approximately 10 percent of the total DNA in the mother’s plasma. Newer genetic techniques now allow for the genetic evaluation of the origin of this DNA to detect alterations in the number of fetal chromosomes without requiring a diagnostic procedure, such as amniocentesis or chorionic villus sampling.
By analyzing those fragments, obstetricians can detect evidence of such conditions as Down syndrome; other chromosomal anomalies, including trisomy 18, also known as Edward syndrome, or trisomy 13 (Patau syndrome); sex-linked conditions; and Rh incompatibility between woman and fetus.
In a study of 18,500 pregnancies, researchers at Columbia and the University of California, San Francisco, found that one such test is more accurate than conventional screening at identifying Down syndrome.
“This study supports the use of noninvasive prenatal testing as a firstline screening option for any pregnant woman, regardless of the patient’s age or whether the patient is low, average, or high risk,” says Ronald Wapner, MD, director of reproductive genetics at Columbia and one of the principal investigators of the study. Dr. Wapner led the study with Mary E. Norton, MD, at UCSF.
Tests that detect fetal DNA in maternal blood were first introduced in 2011 but have been investigated mostly in high-risk women—those who are over age 35 or who have genetic risk factors. This study supports the use of noninvasive prenatal testing as a first-line screening option for any pregnant woman.
The new study is the first in the general pregnant population that is large enough to compare the performance of the new DNA test with conventional screening. The researchers tested a DNA test offered by Ariosa Diagnostics, but other companies market similar tests.
The researchers found that the new test correctly identified more Down cases—with far fewer false positives—than standard screening that combines blood tests with an ultrasound exam.
The DNA test identified all 38 cases of Down syndrome and produced only nine false positives (0.06 percent). Standard screening identified 30 of the 38 cases of Down syndrome and produced 854 false positives (5.4 percent).
About 3 percent of the DNA tests did not produce a result, often because the fraction of fetal DNA in the blood sample was too low. These participants had a higher frequency of Down syndrome cases as well as other chromosomal abnormalities, and further study is needed to determine the best approach for these patients.
Before the DNA test can be widely used in patient care, people’s expectations of the test should be carefully considered, the authors say. The test is highly accurate at detecting Down syndrome and other conditions with extra chromosomes, but standard screening and diagnostic testing can identify a broader array of abnormalities not detectable with the cell-free DNA test.
Mary E. D’Alton, MD, the Willard C. Rappleye Professor of Obstetrics & Gynecology and chair of the Department of Obstetrics & Gynecology, is an expert in maternal fetal medicine and has long promoted monitoring and technology that will improve pregnancy outcomes. “This research is further evidence of Columbia’s unique ability to identify ways to give parents an accurate picture of their baby’s medical condition and create the best management plan,” says Dr. D’Alton.
This is a summary of research published in the New England Journal of Medicine, April 23, 2015.