This summer, I sat on the beach with two new mothers and their infants
and listened to them swap pregnancy and birth stories, as new mothers are wont to do. I chimed in with a few highlights from my two pregnancies, including one story about my amniocentesis and when, at all of 18 weeks in utero, the fetus that would become my daughter Juliette reached into the black void on the screen in front of me and grabbed the needle. Then I asked if either of them had had an amnio and was shocked when they both said no, despite the fact that at the ages of 36 and 43 they are considered to be of “advanced maternal age.” I then asked if either of them had been given a nuchal translucency to determine whether or not the fetus might have a chromosomal anomaly like Down syndrome. “Oh no,” they explained. “They don’t do that anymore. There’s a new test.”
Seven years ago, when I had my first baby, the nuchal translucency was the new test—so new that while I had it in New York City, it was not offered to my friends in other parts of the country. By the time I was pregnant again, the nuchal had followed me out to the ‘burbs. But, apparently, in the three years since then it has been usurped by something that is newer, better, and done earlier in a pregnancy. I’d already planned to find out more when my cousin called to announce she was nine weeks pregnant with a boy. “If you’re only nine weeks along,” I asked, “how do you know it’s a boy?” “Oh,” she explained, “there’s this new test.”
The new test—which is marketed under the brand names MaterniT21, Harmony, verifi, and Panorama—is referred to as cfDNA testing because
it is an analysis of cell-free fetal DNA found in the pregnant person’s blood. The test requires a simple blood draw from the mother. Fragments of fetal DNA—which makes up between 3 and 13 percent of the pregnant person’s blood during pregnancy but disappears entirely right after delivery—are isolated and analyzed for chromosomal abnormalities, including Down syndrome (also known as trisomy 21), Edward syndrome (trisomy 18), and Patau syndrome (trisomy 13), all of which can cause serious developmental and medical issues. (All of these anomalies fall under the category of fetal aneuploidy, which refers to any condition in which there are too many or too few chromosomes.) As an added bonus, the test, which can be given as early as nine weeks into a pregnancy, can reveal the fetus’ gender.
Interestingly, some cfDNA tests can also detect anomalies of the sex chromosomes, such as Turner syndrome (in which a fetus develops with only one X chromosome instead of the normal XX female or XY male), Klinefelter syndrome (XXY), Triple X syndrome (XXX), or XXY. (For more on these chromosomal anomalies that affect gender, see RH Reality Check’s article “The Biology of Gender.”)
Research on the tests show that they have 98 percent ability to screen for Down syndrome and a very low rate (0.5 percent) of false positives. In one study of over 1,000 pregnancies in the United Kingdom, the rate of false positives came in at 0.1 percent.
This new testing method is preferable to the existing methods for a number of other reasons as well. Obviously, a blood test is less invasive than an amniocentesis, in which a physician sticks a large needle through a woman’s stomach into her uterus in order to retrieve amniotic fluid for testing. Another test, called Chorionic Villus Sampling (CVS), is also invasive as it involves going through the cervix to get a small sample of the placenta. Though the results of these tests are definitive (they provide a firm diagnosis) both carry a small risk of miscarriage (estimated at less than 1 percent). These are also conducted later in the pregnancy; CVS can be done between 10 and 12 weeks, amniocentesis between 15 and 20 weeks.
The “combined test,” which includes the nuchal translucency and one or two blood tests, was considered a major step forward for prenatal testing. It can be done at 11 weeks and is not at all invasive. In the ultrasound, the technician measures the space at the back of the fetus’ neck. This “translucent” space tends to be larger in fetuses with genetic anomalies, because fluid often accumulates behind their necks. Technicians also look for the presence of a nasal bone, which is another sign of normal development.
One major issue with the combined tests is that the results can be confusing, because they are presented as a probability. For example, based on age alone, a 30-year-old woman has a 1 in 1,000 chance of having a baby with Down syndrome. Using her age, the measurements taken during the ultrasound, and results from the blood test, the combined test comes back with a more personal probability. It may lower her risk to 1 in 4,000, or raise it to 1 in 250 or 1 in 30. As the March of Dimes explains, the test cannot “diagnose” Down syndrome or other birth defects but instead “helps identify pregnancies that are at higher-than-average risk of Down syndrome.”
Without a yes or no answer, the woman and her partner then have to decide if the results are within their own comfort zone or if they want to have further testing done, such as an amnio or CVS. Though everyone has their own benchmark (the test is often marked “normal” if it comes back as better than 1 in 250), my obstetrician essentially told me that if my odds were better than average for my age, I didn’t need any further tests, but if they were worse I should consider it. (I took this advice in my first pregnancy, when I was 34, but the second time around, at 38, I got nervous and asked for the amnio despite good results on the combined test.)
In a blog post on the Huffington Post, perinatologist Adam Wolfberg, argues that this presentation of results is just too confusing for patients.
Hundreds of my patients over the years have looked at me with a blank face when I said: “Your screening result says you have a 1 in 700 risk of having a baby affected by Down syndrome.” They had no idea what I meant. I would try to explain it lots of different ways, but frequently, I knew I had failed to communicate the meaning of that risk.
The results of cfDNA tests are more definitive and easier to understand, though each brand presents them differently. The verifi test, for example, simply notes whether any aneuploidy was detected and which one, while Panorama categorizes pregnancies into low-risk or high-risk based again on a woman’s personal probability for any of these conditions. According to BBC News, however, these results are markedly different than for the older tests. Low risk for Down syndrome, for example, means that the chance that the fetus has Down syndrome is less than 1 in 10,000. Kypros Nicolaides, a researcher who helped develop both the nuchal translucency and this new test, told BBC News over the summer, “This test is nearly diagnostic. It tells you almost certainly your baby has Down’s or almost certainly it does not. From a woman’s perspective, that is a much more clear message about what to do next.”
Others caution that it’s still not that easy. Dr. Michael Mennuti, chief of reproductive genetics at the Hospital of the University of Pennsylvania in Philadelphia, told the American Journal of Medical Genetics that each lab is going to have to make its own determination of where to draw the low-risk/high-risk line. “A patient with a normal pregnancy could have numbers just above the cutoff, but the lab would report her as high risk,” said Mennuti. “Likewise, a patient with numbers just below the cutoff could have an affected pregnancy but be considered low risk.”
For this and other reasons, medical groups are approaching this new test with caution. The American Congress of Obstetrics and Gynecologists (formerly the American College of Obstetricians and Gynecologists) along with the Society for Maternal-Fetal Medicine released an opinion in December 2012 that said the test was promising but should not yet be part of the routine lab work for normal pregnancies. Instead, it should be reserved for women who are 35 or older, those with a history of trisomy, and women carrying a fetus that shows abnormalities on an ultrasound consistent with trisomy. The groups explained that there is not sufficient research on the test in low-risk women or women carrying multiples to recommend it for these groups. Finally, the groups concluded, “Cell free fetal DNA does not replace the accuracy and diagnostic precision of prenatal diagnosis with CVS or amniocentesis, which remain an option for women.”
Consistent with these opinions, some experts have expressed concerns that women will not understand the limited scope of the test or appreciate that good results do not guarantee a healthy baby. Others worry that the high levels of accuracy and low numbers of false positives—which are based on laboratory studies—will deteriorate once the test is widely used by doctors and laboratories. There is also a concern that the test will be performed and results will be provided without sufficient counseling to help expectant parents understand the outcomes and make decisions based on those outcomes.
In her recent article for the Huffington Post, Katherine Bindley tells the story of one woman who was told her baby would be born with Down syndrome on the phone while sitting alone in her car. Others talk of being given the run-around when trying to ask questions, with genetic counselors referring them back to their obstetricians and obstetricians suggesting they speak to genetic counselors or pediatricians. Getting the results of these prenatal tests early may make decisions about whether to continue a pregnancy easier for some women, but it is still important that all patients have access to counselors who can help them process the news and make the best choice for themselves and their families.
Even with these cautions, many predict that this new test will soon become the norm. Dr. Wolfberg explained that at his institution, South Shore Hospital in Massachusetts, they started by offering patients a choice: the combined test, including the nuchal translucency, or the new cfDNA test. Patients, however, got confused and couldn’t understand why they were offering the older test if a newer, better one was available. So they stopped offering it. He believes others will follow suit. ”My hunch is that obstetricians on the front lines—the ones who counsel pregnant women every day about their testing options—will realize that the new tests are just plain better,” Wolfberg said. “Patients of all ages—who can inform themselves more easily than ever before—will demand them too.”