When Ramona Burton became pregnant with her second child this year, the 37-year-old Upper Marlboro, Md., woman knew that her age put her baby at an elevated risk for Down syndrome, even though screening with ultrasound and standard blood tests raised no warning flags.
Ms. Burton and her husband didn't want to risk amniocentesis, the gold standard for prenatal diagnosis, because it carries a small chance of miscarriage. So when her doctor offered an alternative — a new test that requires only a sample of the mother's blood — they leapt at it. In less than two weeks, they got the news: no Down syndrome. The baby, a boy, is due next month.
Three versions of this test, which can be performed as early as 10 weeks into a pregnancy, have come onto the market since December.
Tens of thousands of women have used them, according to the companies that sell the tests. But they are not subject to regulation by the Food and Drug Administration, and questions have been raised about a technology whose accuracy and role are still being assessed. As a result, no major insurance company has yet agreed to cover the tests, whose list prices range up to $1,900.
New medical technologies often challenge a health-care industry grappling with pressures to control costs. It's not yet clear whether the new tests will cut costs and miscarriages by reducing invasive prenatal diagnostic procedures such as amniocentesis or inflate costs because they're used by women who probably would never have opted for amnio because of miscarriage fears.
(The established tests are performed about 200,000 times annually in the United States and cost roughly $2,500 in the Washington area.)
With the new tests, fragments of fetal DNA extracted from the mother's blood sample are checked for increased amounts of material from chromosomes 21, 18 and 13, a sign that the fetus carries three instead of the normal two copies of those chromosomes.
In this case, more is not better. Having an extra copy of 21, a condition called trisomy 21, is the main cause of Down syndrome, while having a third copy of 18, a condition called trisomy 18, causes a less common disorder named Edwards syndrome. Trisomy 13 is also known as Patau syndrome. All three conditions are linked to serious developmental and medical problems.
Standard first-trimester screening for these genetic conditions can be performed as early as 11 weeks' gestation. It consists of a blood test to check levels of pregnancy-associated proteins and hormones in the mother's blood and an ultrasound to look for extra fluid under the skin at the back of the fetus's neck. The results are usually available within a week.
Used together, the standard blood tests and ultrasound can detect about 90 percent of Down syndrome cases and an even greater proportion of trisomies 18 and 13. But there's a false-positive rate of about 5 percent, and only amniocentesis or the much less commonly used chorionic villus sampling, another invasive test that can cause miscarriage, can provide a definitive answer.
The new blood tests that assess fetal DNA rather than maternal blood perform better than standard screening, says Tufts scientist Diana Bianchi, whose research helped lay the groundwork for them. Bianchi sits on the scientific advisory board of Verinata Health, which launched its test, called Verifi, in March. "The problem is they're more expensive, so they can't be a primary screen," she says.
The tests generally are offered only to women whose age, family history or standard screening put their fetus at a higher risk of having a chromosome abnormality — not to all women, as the standard screening tests are.
So far, major insurance companies, citing limited studies about the tests' accuracy and impact on patient care, consider them to be experimental and do not cover them. (Sequenom, the marketer of the MaterniT21 Plus test, asserted this month that 15 percent of the U.S. population is covered by plans that will pay for the test, though it did not identify those plans.)
The American College of Obstetricians and Gynecologists published its first opinion on the tests Nov. 20 and concluded they "should not be part of routine prenatal laboratory assessment." However, ACOG said, the tests can be offered to patients at increased risk of having a baby with a trisomy, as long as they are counseled beforehand about the tests' limitations. Previously, the National Society of Genetic Counselors and the International Society for Prenatal Diagnosis reached similar conclusions.
Because research has not yet proved that the new tests are as accurate as the standard invasive tests, all three organizations recommend that women with a positive result undergo amniocentesis or chorionic villus sampling to be sure.
"We clearly take ACOG's opinion into consideration as we evaluate coverage policy," says Julie Kessel, senior medical director of Cigna's coverage policy unit. But, she adds, "it's not a clear endorsement."
Cigna typically reviews coverage of technologies annually, unless a "sentinel event," such as firm new guidelines about their use, suggests the company needs to take another look sooner, Kessel says. The ACOG opinion is not such an event, she says, so the company likely won't revisit the blood tests until July.
Aetna spokeswoman Tammy Arnold says her company is awaiting the results of more research into the tests' accuracy and how testing affects women's decisions about amniocentesis. Once studies of patients prove that the tests add value, Arnold says, "cost savings to the health-care system would be a welcomed bonus."
Women are asking for the tests right now, however. "I don't think anybody really anticipated that the consumers would drive this as much as they're doing," Bianchi says.
For now at least, the companies that market the new tests appear to be eating much of the cost. For example, the most that women with insurance have to pay out of pocket is $235 for the MaterniT21 Plus test (list price $1,900) and $200 for Verifi (list price $1,200), even if their plan declines to cover the test. Both companies offer self-pay options for women without insurance: The price is $450 to $500 for MaterniT21 Plus and an "introductory price" of $495 for Verifi.
Jeffrey Spencer, Ramona Burton's OB-GYN at the Anne Arundel Medical Center in Annapolis, Md., says that although questions remain about how best to use the tests, he needs to make his patients aware of them. "It's so new we're not sure the best way to do it. I feel I have an ethical obligation to make patients aware of the option." (Dr. Spencer says he is a member of the speakers' bureau of Sequenom, which markets the MaterniT21 Plus test, and is paid a fee when he speaks at the company's request.)
Ms. Burton is one of several hundred higher-risk patients in his practice who have opted for MaterniT21 Plus, Dr. Spencer says.
Mark Evans, a Manhattan OB-GYN, says his patients want to skip the standard screening tests and go right to the new tests. "My patients are the average New Yorkers," he says, "who want their answers yesterday."