Prenatal Assay Might Be Alternative to Risky, Invasive Prenatal Tests

The prenatal genetic tests amniocentesis and chorionic villus sampling (CVS) are now used to reliably diagnose Down syndrome and other conditions resulting from aneuploidy, an abnormal number of chromosomes. But these tests involve inserting a needle into the uterus, with a miscarriage risk of roughly half a percent. The new approach, described in the October 6 issue of the Proceedings of the National Academy of Sciences, determines whether the fetus has aneuploidy by testing a sample of the mother’s blood for pieces of fetal DNA.

The new technique may be especially important following changes in recommendations in aneuploidy testing from a respected organization of obstetricians. For years, obstetricians offered the invasive tests primarily to women 35 and older, then considered especially at risk for carrying a fetus with an abnormal number of chromosomes. But in 2007, the American College of Obstetricians and Gynecologists suggested that obstetricians offer a first trimester screen to all pregnant women, regardless of age, and perform invasive follow-up testing if necessary. (See the March 2007 article, ACOG Releases New Guidelines for Screening Tests Recommended During Pregnancy.) The researchers write that their test could “presumably carry the best of both worlds: minimal risk to the fetus while providing true genetic information.”

Their technique counts the baby’s chromosomes using bits of fetal DNA in a pregnant woman’s blood. While other researchers have also developed tests that can diagnose aneuploidy from the blood, these assays have been shown to be effective only in particular populations with specific genetic variations and require distinguishing fetal DNA from maternal DNA, the PNAS article notes. The newly developed method requires no such distinction.

Using samples from 12 women with aneuploid pregnancies and six with normal pregnancies, the research team separated maternal blood into cells and plasma. After discarding the blood cells, the team examined DNA fragments from both the mother and fetus in the liquid plasma. After counting the number of DNA fragments and analyzing them for each woman, the researchers found that women with Down syndrome pregnancies had more chromosome-21 fragments in their blood than women with normal pregnancies. The test identified Down syndrome as early as 14 weeks of pregnancy and revealed other chromosomal abnormalities that also cause serious problems.

"This technique is on the leading edge of a flood of different ways that rapid DNA sequencing will be used in medicine," said senior author Stephen Quake, PhD, professor of bioengineering at Stanford. "Non-invasive testing will be much safer than current approaches."

However, the test will not be available any time soon. The researchers note that they must validate their technique in a much larger number of women, a process that could take years. But if the current findings are confirmed and the test receives approval from the FDA, using the test would be simple and inexpensive, relative to current tests for diagnosing aneuploidy, they write.

Sources

Fan, H. Christina et al. Noninvasive diagnosis of fetal aneuploidy by shotgun sequencing DNA from maternal blood. Proceedings of the National Academy of Sciences 2008; 105: 16266 –16271. Available online at http://www.pnas.org/content/105/42/16266.full.pdf+html. Accessed October 28, 2008.

Stanford University News Release. "New Prenatal Test for Down Syndrome Less Risky than Amniocentesis, Stanford/Packard Scientists Say." Available online at http://med.stanford.edu/mcr/2008/down-test-1008.html. Issued October 6, 2008. Accessed October 28, 2008.