A safer and earlier way to determine if a fetus has Down syndrome is being studied

Women may soon be able to find out very early in their pregnancies whether they are carrying a fetus with Down syndrome by offering a simple blood sample.

The safe, noninvasive test would pose fewer risks to the mother and fetus than amniocentesis or chorionic villus sampling (CVS), the two tests currently used for prenatal diagnosis. It would also give women more time to decide what to do if a diagnosis of Down syndrome is made.

Researchers from the Chinese University of Hong Kong have been working on the DNA-based test for a decade. In their largest study yet, the researchers analyzed blood samples from 753 pregnant women; the test identified every case of Down syndrome and produced only a handful of false positives.

“We’re aiming to provide safe and accurate information to couples,” says study leader Rossa Chiu, who published the results online this month in the British Medical Journal.

A test could be available as early as next year.

However, the study raises important ethical questions about whether couples should be able to access genetic testing for a variety of traits — such as health or eye color — and whether the results will lead to an increase in abortions, thus thinning the ranks of certain kinds of people from the population.


The researchers used blood samples — most taken around the 13th week of pregnancy — from women who later underwent amniocentesis or CVS. Had it been a real-life scenario, Chiu said, “we could have told 98% of the women [who had negative results from invasive testing] that their babies were not Down syndrome.”

Down syndrome is a physical and mental disorder caused by extra DNA. In most people, DNA is packaged into 23 chromosomes that come in neat pairs. But occasionally chromosomes come in triplets or singletons. Down syndrome occurs when there are three copies of chromosome 21 instead of the usual two. The excess DNA causes changes including low muscle tone, short stature and delayed cognitive development. People with Down syndrome can live to age 60 or older.

To test for the extra chromosome, doctors usually extract a sample of fetal DNA. In amniocentesis — available after 15 weeks of pregnancy — the sample is removed from amniotic fluid with a long needle that pierces the uterus. In CVS — done between nine and 14 weeks — doctors remove a piece of tissue from the placenta via a needle or a vaginal tube. Both tests are more than 99% accurate, but both cause a miscarriage in about 1 in every 200 cases. Other risks include infection and amniotic fluid leaking from the uterus.

The new test measures fetal DNA flowing through the mother’s bloodstream. As a fetus develops, some of its cells naturally die. For example, fetuses start out with webbing between the fingers and toes; the webbing is later shed. Pieces of DNA from those dead cells reach the mother’s bloodstream through the placenta, where they join with mom’s fragmented DNA.

Chiu and her colleague Dennis Lo have long aimed to count fetal chromosomes based on these fragments in a pregnant woman’s plasma, but they had to wait for DNA sequencing technology to catch up with their goal. Now scientists can sequence millions of DNA molecules quickly and relatively cheaply.

The researchers use the sophisticated technology to read and identify DNA fragments from a 5- to 10-milliliter sample of blood (about 1 to 2 teaspoons). Metaphorically, they plop each identified piece — whether maternal or fetal — into a “bin” according to the chromosome it came from. If the chromosome 21 bin has more than its fair share of fragments, then the scientists reason that the fetus has Down syndrome.

In their latest study, the Hong Kong researchers collaborated with hospitals worldwide to acquire blood samples from women already considered high risk. Women who are 35 or older, have had a previous pregnancy with a chromosomal abnormality or had suspicious hormone level or ultrasound results are usually considered to have increased risk of carrying a fetus with Down syndrome.

Chiu and Lo’s test correctly identified all of the 86 Down syndrome cases. It also mistakenly flagged three cases as possibly Down syndrome, though amniocentesis or CVS revealed that the fetuses were healthy. Chiu envisions the blood test as a way to identify women who can skip the more invasive (and riskier) procedures.

“It adds more support to the notion that this is going to become a test someday,” says Stephen Quake, a biophysicist at Stanford University in Palo Alto who has also worked on a blood test for Down syndrome but was not involved in the new study. “I think eventually this will replace the amnio,” he said.

Sequenom Inc. has licensed the technology from the Hong Kong university and expects to make the test available to high-risk women by early 2012. The San Diego company started its own study at the beginning of January and expects to test about 2,000 samples by the middle of the year, says spokesman Ian Clements.

Sequenom is not ready to discuss pricing, Clements said, but Quake speculated that, with DNA sequencing getting cheaper by the day, the blood test will likely cost less than the approximately $1,500 price tag of amniocentesis or CVS.

Chiu says her only goal is to make prenatal diagnosis safer, but the work raises many ethical issues.

Given the safety and convenience of a blood test, it’s likely many more women would get tested for Down syndrome, says Dr. Brian Skotko, a physician in the Down Syndrome Program at Children’s Hospital Boston. Thus, many more women may face a choice about pregnancy termination, says Skotko, who has a sister with Down syndrome. [In the interest of full disclosure, I should note that I also have a sibling with Down syndrome.]

Skotko worries that many women do not get all the information they need to make such a decision. In a 2006 study in the journal Obstetrics & Gynecology, researchers found that 20% of obstetricians say they are unqualified to provide genetic counseling to patients, and nearly half say their residency training in prenatal diagnosis was inadequate.

Although Down syndrome may be among the earliest genetic blood tests, more are sure to follow, and that will force doctors, patients and regulators to grapple with difficult questions, Henry Greely, director of the Center for Law and the Biosciences at Stanford Law School, wrote this month in the journal Nature.

Should couples be able to use such tests to find out about a fetus’ eye color, talents or temperament? Will detailed testing lead to widespread abortion of imperfect fetuses, and would society devalue disabled people as a result? The time to answer these questions is now, Greely says.