New, noninvasive blood tests are being developed for expectant mothers to find out if their babies have genetic conditions such as Down syndrome, without the risks of tests available now.
Pregnant women often opt for a prenatal test called amniocentesis that requires a needle to be inserted through the walls of the abdomen and uterus to draw a sample of the fluid surrounding the fetus. The test is uncomfortable and carries a small risk of miscarriage, as does another invasive test for genetic disorders called chorionic villus sampling, or CVS, that samples tissue from the placenta.
Now, scientists say new tests of fetal DNA sampled from a mother's blood can be used to screen for Down syndrome, which occurs in one in 691 live births and causes cognitive disabilities. The new blood tests could be performed as early as nine weeks into a pregnancy—earlier than amniocentesis—and may be available as soon as the end of this year.
And with the price of gene sequencing and other advanced technology continuing to drop, researchers anticipate noninvasive tests can also be used to detect other inherited diseases such as cystic fibrosis or sickle-cell anemia. Researchers at the Chinese University of Hong Kong led by Dennis Lo have published studies showing they can detect beta-thalassemia, a genetic blood condition, and hemophilia by analyzing fetal DNA.
"This is a paradigm change for screening and testing,'' said Michael T. Mennuti, a professor of obstetrics and gynecology at the University of Pennsylvania Medical School who was chairman of a panel that reviewed the results of a clinical trial of one of the fetal-DNA blood tests.
Down Syndrome Developments
• Over 400,000 people in the U.S. live with Down syndrome.
• One in every 691 babies is born with the condition.
• A 35-year-old woman has a 1 in 350 chance of having a child with Down syndrome. The risk rises to 1 in 100 at age 40, and 1 in 30 at age 45.
• People with Down syndrome have an increased risk for heart defects, respiratory problems and other ailments, though many of these conditions are now treatable.
• The life expectancy for people with Down syndrome has risen to age 60 today, up from just 25 in 1983.
Source: The National Down Syndrome Society
Amniocentesis is used to detect several genetic and chromosomal conditions, while the blood tests, at least initially, will screen only for Down syndrome. The new tests could be incorporated into or even replace current, first-trimester screenings, some of which can prove inconclusive and result in women being sent for unnecessary invasive tests.
No one expects such tests to immediately replace amniocentesis, which is considered the gold standard for acquiring definitive genetic information and is performed around 200,000 times a year in the U.S. alone. If the new tests are adopted, eventually only women who find a fetus has a condition would need to confirm the results with an invasive procedure.
Expectant parents choose to undergo prenatal testing for many reasons, including to decide whether to terminate a pregnancy.
Some women decline amniocentesis because of the estimated 1% risk of miscarriage, while others reject it because they wouldn't terminate a pregnancy, regardless of the test's results. Some members of the Down syndrome community have said they fear the new tests might prompt women to terminate their pregnancies based on faulty or incomplete information.
Researchers are also developing noninvasive screening tests for adult ailments. Sequenom Inc., which said it will bring out a noninvasive Down syndrome test early next year, recently started offering a blood or cheek-swab test for the risk of developing age-related macular degeneration, which leads to vision loss.
Stephen Quake, the co-founder of two companies launching noninvasive Down-syndrome tests, is also part of a team of Stanford University researchers which in April published a paper on a way to monitor organ-transplant rejection by tracking the DNA of a donated organ in the recipient's blood.
Cancer researchers are also testing ways to avert the need for biopsies, by detecting tumor DNA in blood.
Sequenom, Verinata Health Inc. and LifeCoddexx AG—a unit of Germany's GATC Biotech—all said they plan to offer prenatal tests by end of 2011 or beginning of 2012. Fluidigm Corp. and Novartis AG, which are partners in the development of a noninvasive Down syndrome test, said they don't have a launch date yet.
Philippos C. Patsalis of the Cyprus Institute of Neurology and Genetics said his team is developing a noninvasive method to test for Down syndrome by comparing fetal DNA to the mother's using standard lab equipment, instead of pricey gene-sequencing gear.
The current crop of noninvasive tests grew out of a discovery made in the late 1990s by Dr. Lo at the Chinese University of Hong Kong. He found a fetus releases its DNA into the plasma of the mother during pregnancy, though within two hours of giving birth, the baby's DNA vanishes.
Fetuses with Down syndrome have three, rather than two, copies of chromosome 21. Scientists figured that screens could detect an affected fetus by measuring the presence of elevated amounts of chromosome 21 sequences relative to other chromosomes.
Fetal DNA represents only 5% to 15% of the total DNA circulating in the mother's blood, researchers said. But recent technological advances and the development of sophisticated algorithms now make it possible to parse millions of DNA fragments in a matter of days.
In a paper published earlier this year in the British Medical Journal, Dr. Lo and his co-researchers showed they could find all 86 cases of Down syndrome in testing done on 752 pregnant women. These were high-risk women who underwent either amniocentesis or CVS, which confirmed the findings of the blood test.
Dr. Mennuti, who treats pregnant women, said many questions about the new tests remain, adding it would be important to confirm any positive result with amniocentesis.
Sequenom said it hasn't set the price of its test, but that it would fall within the $1,500-$3,000 range that amniocentesis and CVS cost.
Stanford's Dr. Quake said he started thinking about the need for noninvasive tests when his wife was pregnant with their first child. His wife was over 35 years old and her doctors recommended amniocentesis.
"It was a nerve-wracking experience, watching the needle go in and having to think about the risks to the baby that went along with it," he said.
Write to Amy Dockser Marcus at email@example.com