A large new study led by Boston researchers shows that a simple blood test is more accurate than the standard methods to screen for chromosomal abnormalities such as Down syndrome in a fetus, paving the way for a new generation of prenatal genetic tests to be offered to all pregnant women.
The research published Wednesday is the first US study to compare these new genetic tests with current screening tools in large numbers of low-risk pregnant women. It found the new tests produced far fewer false positive readings.
The findings could lead to more women being screened and more abnormal fetuses being identified at an early stage of pregnancy — when parents could choose to terminate the pregnancy.
It also means many pregnant women could be spared invasive tests, such as amniocentesis, that are performed to confirm positive screening results and carry a small risk of miscarriage.
Ethicists and the study authors say that the expanding capabilities and adoption of the technology call for a broader societal discussion about how prenatal tests should be used. The tests analyze fragments of fetal DNA that enter the mother’s blood from the placenta, a process that could one day be used to detect susceptibility to numerous diseases and conditions, as well as traits such as eye color.
“It’s different if you’re a child with a mysterious disease and have your genome sequenced. That’s very clear that you’re doing it at that point to help that person,” said Dr. Diana Bianchi, who led the study and is executive director of the Mother Infant Research Institute at Tufts Medical Center. “It’s unclear at this point whether someone will want to look into a crystal ball and find out absolutely everything about their future child’s life.”
The study, published in the New England Journal of Medicine, was funded by Illumina, a DNA sequencing company that offers a prenatal test that costs $1,500. That test is one of four prenatal blood tests that have become available since 2011 to screen for conditions in which a fetus has abnormal numbers of chromosomes. Bianchi is a member of Illumina’s clinical advisory board and receives an honorarium from the company, but holds no stock.
Other studies of the technology are underway and if they reach similar conclusions, it’s expected that they will eventually lead to wider use of the new tests, which several medical organizations now recommend be offered only to women with high-risk pregnancies.
In the Tufts study, nearly 2,000 pregnant women were tested with both typical screening, which includes ultrasound and a biochemical blood screen, and with the fetal DNA tests. With the typical screening, 3.6 percent of the women received a false positive result, meaning the test indicated they had a fetus with Down syndrome when the fetus was normal. With the new technology, just 0.3 percent of women incorrectly got a positive result. The false-positive rate was also better for a chromosomal disorder called Edwards syndrome — 0.6 percent for the standard test versus 0.2 percent for the new technology.
The tests were still far from conclusive for any individual woman. For a woman who got a positive Down syndrome result, there was a 45.5 percent chance the prediction was correct — about 10 times better than the standard test, but still far from a firm diagnosis. That is why researchers emphasized that the invasive procedures, such as amniocentesis, would still be necessary to confirm a positive result. Of the eight fetuses identified with chromosomal abnormalities during the study, only one pregnancy was terminated.
Dr. Nancy C. Rose, a chair of the committee on genetics for the American Congress of Obstetricians and Gynecologists, said in an e-mail that the study was encouraging but limited and that additional studies would be needed before broader adoption of the tests was recommended by her group.
The Down syndrome advocacy community, however, has already been preparing for wider use of the test. The Massachusetts Down Syndrome Congress, for example, has revised its Parents First Call program, which provides resources for parents of children with the condition, to place greater emphasis on prenatal diagnosis and expectant parents.
If the tests “become a routine offering during obstetric care for couples, we need to ask the question, will babies with Down syndrome slowly start to disappear?” said Dr. Brian Skotko, co-director of the Down Syndrome Program at Massachusetts General Hospital, who was not involved in the study and has a sister with Down syndrome. The tests “raise the ethical question of which conditions can and should be tested for prenatally . . . And as science evolves, we need to ask: should prenatal testing include autism, breast cancer risk genes, or even one’s sexual orientation?”
Amy Ackerson, 39, from Sudbury, received a standard screening test four years ago when she was pregnant with her first child. The test gave her a low risk for Down syndrome. But in follow-up appointments, a possible heart issue was detected and a more detailed ultrasound led to the identification of two other features of Down syndrome. She consented to an amniocentesis.
Ackerson and her husband found out their baby would have Down syndrome and decided they would move forward with the pregnancy. Although the process and conflicting results were agonizing, Ackerson appreciated the information — it helped her prepare for the birth of Chase, a happy, social 3-year-old who is called “the mayor” at his preschool.
Expecting her second baby this spring, Ackerson was offered one of the new genetic blood tests — one that she was happy to get because she was told it would be more accurate than the one that had led her through such a confusing maze of emotions the last time.
“Speaking as someone who is currently pregnant, I think the blood test is a good first line, absolutely,” Ackerson said. “I say that with the caveat, though, that it does need to come with information.”
Ackerson said she spoke with a genetic counselor and felt she was given good resources during her first pregnancy, but it still felt overwhelming.
“I think noninvasive prenatal testing is likely to be very, very widely adopted,” said Hank Greely, director of the center for law and the biosciences at Stanford University. “I think that is likely to lead to some increase in the number of Down syndrome fetuses that are aborted. How big an increase, I don’t think we know.”
Anne Fox, president of Massachusetts Citizens for Life, said it’s helpful for parents to get more accurate test results but the issue was a complex one.
“If the only purpose of the test is to find out if the child has something that cannot be helped prenatally, I think we have to think about why we’re doing it,” Fox said.
As science evolves, the questions will only get bigger.
“This technology is certainly only in its infancy as the range of testable conditions expands, physical conditions, cognitive conditions, even behavioral ones,” said Dov Fox, an assistant professor of law at the University of San Diego School of Law. “That will only further complicate how parents decide what counts as healthy or acceptable in the children that they have.”