What Noninvasive, Early Fetal Tests Mean for Pregnancy, Abortion, and More

What's to come?
April 27 2012 7:30 AM

Will Gattaca Come True?

Noninvasive, early fetal tests for sex, paternity, and chromosomal conditions will change pregnancy dramatically—and raise tricky ethical questions.

Early fetal diagnostic tests.
Natera is one of several companies vying to commercialize fetal DNA tests, or noninvasive prenatal diagnosis

Photograph by Comstock.

In 2003, back when such things remained unpredictable, a woman gave birth to a baby boy with Down syndrome. Her family was shocked. She had undergone the standard screening tests while pregnant—a blood test followed by an ultrasound—but the results had come back negative. Nor did she have the risk factors associated with Down, like advanced maternal age; she was 32. “She was not prepared for this,” recalls Matthew Rabinowitz, her brother. When the boy died six days later, his mother was devastated.

The event left a deep impression on Rabinowitz. A young Silicon Valley entrepreneur who had recently left Stanford with a Ph.D. in electrical engineering, he had just sold the second of two successful IT startups and was casting about for a new venture. Current methods of prenatal screening carry a significant margin of error, and his sister’s false negative suggested an opportunity. “I saw that we were applying our information technology and signal processing to various aspects of life, including cell phones and laptops, but not enough to the area of helping parents have healthy children,” says Rabinowitz.

A scientist in Hong Kong had recently shown that a pregnant woman’s blood contains a small amount of fetal DNA, and the prenatal screening world was buzzing about the potential of that discovery. Accurate blood tests, it was said, might soon reveal abundant information about the fetus as early as seven weeks of pregnancy. Rabinowitz drew on that excitement in 2004 when he founded Gene Security Network, later renamed Natera. Among the tests the company would develop was one to diagnose Down syndrome.

That test, called Parental Support, is currently in trials funded by the National Institutes of Health. Natera is one of several companies vying to commercialize fetal DNA tests, or noninvasive prenatal diagnosis (NIPD). A few years ago, a handful of these companies began offering NIPD to determine fetal sex and detect Rh-factor incompatibility—left undiagnosed, a woman with Rh-negative blood carrying an Rh-positive baby can produce antibodies that attack the baby’s blood cells. Recently, we’ve seen a new wave of NIPD applications: Beginning last fall, the San Diego-based company Sequenom rolled out tests for Down syndrome and Trisomies 13 and 18, and Silicon Valley-based Verinata entered the market with tests for the same conditions in March. Rabinowitz expects Parental Support to be available by the end of the year. (He claims Natera’s technology is more accurate than other tests.)

Now insurance companies are getting involved. Last week, Sequenom announced a partnership with the managed health care company MultiPlan, and others are marketing heavily to insurers. The tests currently available still carry a margin of error and thus can’t yet be sold as a replacement for the likes of amniocentesis. Even as a supplement to existing methods, though, NIPD could be commonly used with high-risk women, predicts an article in the April issue of the insurance industry magazine Managed Care. And as companies like Sequenom and Natera boost their accuracy rates, Managed Care says, NIPD  “has potential to become a standard screening procedure.” Because blood tests are less invasive than existing screening methods, and because they help insurers avoid the long-term costs of caring for people with expensive medical conditions and disabilities, they aren’t a hard business sell.  

The potential benefits of NIPD are many: elimination of the risks associated with amniocentesis, the replacement of aggravating probabilities with accurate information, and more time for expectant parents to make difficult decisions. But because insurance providers have an incentive to cover them, fetal DNA tests stand to be introduced before we have time to consider the slew of ethical and political challenges they will introduce.

Scientists have known for decades that the blood of a pregnant woman contains a few stray fetal cells. In the 1990s, labs began exploring blood-borne fetal cell testing as an alternative to amniocentesis, which carries a risk of miscarriage. But gleaning information from those cells entails the difficult process of distinguishing them from the mother’s cells—and from fetal cells from earlier pregnancies, which can linger in a woman’s blood long after a baby is born.

Then, in 1997, Dennis Lo, a medical researcher at Chinese University of Hong Kong, discovered that the mother’s blood also contains floating strands of fetal DNA unattached to cells. Today scientists commonly believe the fetus contributes about 10 to15 percent of the DNA in the mother’s plasma. Lo licensed a technique of analyzing cell-free fetal DNA, or cffDNA, to Sequenom in 2005, and the batch of tests the company recently introduced are based on his technology.

Lo says an accurate Down syndrome test was originally considered the Holy Grail of prenatal diagnosis. But in the process of reaching that target, scientists also developed methods of determining fetal sex, which is one of the easier qualities to test for—and which became the first commercialized by companies looking to capitalize on Lo’s discovery. While fetal sexing is helpful for couples with a genetic propensity toward sex-linked diseases like hemophilia, companies like Consumer Genetics, DNA Plus, and Prenatal Genetics Center now offer NIPD direct-to-consumer for parents simply intent on getting a girl or boy. In 2005, an early-generation mail-order blood test, Baby Gender Mentor, briefly inspired a media frenzy culminating in an appearance on the Today show—before it was found to be inaccurate. (Disappointed parents filed a class-action suit, and Acu-Gen Biolab, the company offering the test, filed for bankruptcy.)

The latest sex tests will almost certainly wreak havoc on countries with already significant sex ratio imbalances as they spread overseas. When news of Baby Gender Mentor reached India, for example, it sparked an outcry. Sex determination, whether through blood tests or ultrasound, is illegal in India, but many doctors flout the law. And if women can one day obtain results without the help of a physician or technician—by pricking a finger and sending in a spot of blood, as Baby Gender Mentor promised—gynecologist Puneet Bedi says India’s sex ratio at birth would reach a “level unthinkable by any means so far.”  India’s campaigners are prepared to fight the introduction of NIPD. But activist Sabu George says the fledgling anti-sex selection campaign is a poor match for the Goliath of the Western medical technology industry.

When Lo licensed his technology to Sequenom, he stipulated that it could not be used for sex selection. Rabinowitz says Natera won’t test for sex at this point, either. But how long such provisions will hold is unclear. Meanwhile, NIPD’s reach is expanding as the technology used to analyze cffDNA improves. In December 2010, Lo published a paper in Science Translational Medicine showing that in principle, at least, scientists can piece together the entire fetal genome from cffDNA. Lo says that exceeded even his own expectations: “If you asked me prior to 2008, I would have probably said that was science fiction.”

At the time his paper was published, the process cost $200,000. Now, with the cost of DNA sequencing dropping faster than that of computing power, he estimates the bill may come to one-tenth of that—still expensive, but no doubt tempting for some parents. Lo wagers complete fetal genome testing might be widely available in a clinical setting within a decade. What fetal genes might one day suggest about a baby’s eye color, appearance, and intellectual ability will be useful to parents, not insurers. But with costs coming down and insurers interested in other aspects of the fetal genome, a Gattaca-like two-tiered society, in which parents with good access to health care produce flawless, carefully selected offspring and the rest of us spawn naturals, seems increasingly plausible.

There are considerable hurdles to clear still before full fetal genome testing is available in a clinical setting. For the present, Lo envisions tailored packages targeting the 10 to 15 diseases most relevant to a couple’s genetic history. But the ethical and logistical issues raised by accessing even portions of the fetal genome are tricky enough.

How to explain the test to patients is a particularly thorny question. Currently, genetic counselors are brought in only with parents who undergo amniocentesis or other diagnostic tests after finding out the fetus has an elevated risk of, say, Down syndrome. Widespread introduction of NIPD means all parents will need counseling, and without enough counselors to go around, the burden of explaining the test will most likely fall on the OB-GYN(though Verinata provides an in-house genetic counseling hotline). “You’ll have a lot of women with OB-GYNs who are not really trained in genetics who are going to try to explain to them the implications of NIPD,” says Jaime King, a law professor at University of California Hastings College of the Law. “And it’s not just what happens when you get a high-risk result. It’s: Do you even want this testing? And what do you want it for? And do know what you’ll do with the results around a whole range of conditions? That’s not something that women are currently prepared to decide—or that doctors are currently prepared to help them decide.” That may be why in February, the National Society of Genetic Counselors adopted a statement opposing the routine use of NIPD for low-risk women. But since fetal DNA tests are risk-free, some doctors might offer them simply to ward off lawsuits.

More fantastically, the government might require testing. University of Texas-Austin bioethicist John A. Robertson recently outlined, for the sake of argument, a scenario in which states mandate that pregnant women undergo fetal DNA tests to avoid the costs of caring for the disabled people who might otherwise be born. There is constitutional precedent, he pointed out, in requiring suspected drunk drivers to submit to blood tests. (A state would have more trouble forcing women to hear or act on the results, he wrote.)

Marcy Darnovsky, executive director of the Center for Genetics and Society in Berkeley, Calif., notes that NIPD will provide women with “enormous amounts of information about the fetus that they’re carrying at a very early stage. And it’s available at a time when you can terminate a pregnancy with a pill.” In one calculation by the Stanford Law School bioethicist Henry T. Greely, if just two-thirds of pregnant American women undergo NIPD, the number of fetal genetic tests done in the United States will jump from fewer than 100,000 a year to about 3 million. Just what that will do to the abortion rate is impossible to predict—but it probably will rise. (Some experts argue that an increase will be offset by our expanded ability to treat some conditions in utero.)

Even if the overall abortion rate increases, though, it may become more difficult for some women to get abortions. Anti-abortion activists are prepared for the new technology. Think Rick Santorum’s recent tirade about amniocentesis allowing us to “cull the ranks of the disabled” was overblown? It was just the beginning. A recent LifeNews.com article calls NIPD a “seek-and-destroy mission against any life in the womb.”

For instance, pro-life activists might seek to ban Medicaid coverage of NIPD along the lines of the Hyde Amendment prohibition on the use of Medicaid funds for abortion—a change that would disproportionately affect poor women.

Just how soon the bulk of insurers will cover NIPD—and transform the discussion surrounding pregnancy and abortion in the process—is still unclear. A lot will depend on the accuracy rates to come out of trials like Natera’s. If those cement NIPD as a replacement for amniocentesis, the new tests will undoubtedly mean less suffering for women like Rabinowitz’s sister. But for the rest of us, things will get a lot more complicated.

This article arises from Future Tense, a collaboration among Arizona State University, the New America Foundation, and Slate. Future Tense explores the ways emerging technologies affect society, policy, and culture. To read more, visit the Future Tense blog and the Future Tense home page. You can also follow us on Twitter.

Mara Hvistendahl is a correspondent with Science and the author of Unnatural Selection: Choosing Boys Over Girls, and the Consequence of a World Full of Men. Follow her on Twitter here.