When They Warn of Rare Disorders, These Prenatal Tests Are Usually Wrong

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fter a year of fertility treatments, Yael Geller was thrilled when she found out she was pregnant in November 2020. Following a normal ultrasound, she was confident enough to tell her 3-year-old son his “brother or sister” was in her belly.

But a few weeks later, as she was driving her son home from school, her doctor’s office called. A prenatal blood test indicated her fetus might be missing part of a chromosome, which could lead to serious ailments and mental illness.

Sitting on the couch that evening with her husband, she cried as she explained they might be facing a decision on terminating the pregnancy. He sat quietly with the news. “How is this happening to me?” Ms. Geller, 32, recalled thinking.

The next day, doctors used a long, painful needle to retrieve a small piece of her placenta. It was tested and showed the initial result was wrong. She now has a 6-month-old, Emmanuel, who shows no signs of the condition he screened positive for.

Ms. Geller had been misled by a wondrous promise that Silicon Valley technology has made to expectant mothers: that a few vials of their blood, drawn in the first trimester, can allow companies to detect serious developmental problems in the DNA of the fetus with remarkable accuracy.

In just over a decade, the tests have gone from laboratory experiments to an industry that serves more than a third of the pregnant women in America, luring major companies like Labcorp and Quest Diagnostics into the business, alongside many start-ups.

The tests initially looked for Down syndrome and worked very well. But as manufacturers tried to outsell each other, they began offering additional screenings for increasingly rare conditions.

The grave predictions made by those newer tests are usually wrong, an examination by The New York Times has found.

That includes the screening that came back positive for Ms. Geller, which looks for Prader-Willi syndrome, a condition that offers little chance of living independently as an adult. Studies have found its positive results are incorrect more than 90 percent of the time.

Nonetheless, on product brochures and test result sheets, companies describe the tests to pregnant women and their doctors as near certain. They advertise their findings as “reliable” and “highly accurate,” offering “total confidence” and “peace of mind” for patients who want to know as much as possible.

Some of the companies offer tests without publishing any data on how well they perform, or point to numbers for their best screenings while leaving out weaker ones. Others base their claims on studies in which only one or two pregnancies actually had the condition in question.

This isn’t the first time Silicon Valley technology has been used to build a business around blood tests. Years before the first prenatal testing company opened, another start-up, Theranos, made claims that it could run more than a thousand tests on a tiny blood sample, before it collapsed amid allegations of fraud.

In contrast with Theranos, the science behind these companies’ ability to test blood for common disorders is not in question. Experts say it has revolutionized Down syndrome screening, significantly reducing the need for riskier tests.

However, the same technology — known as noninvasive prenatal testing, or NIPT — performs much worse when it looks for less common conditions. Most are caused by small missing pieces of chromosomes called microdeletions. Others stem from missing or extra copies of entire chromosomes. They can have a wide range of symptoms, including intellectual disability, heart defects, a shortened life span or a high infant mortality rate.

Not every patient is screened for every condition; doctors decide what to order, and most companies sell microdeletion testing as an optional add-on to the Down screening. Most test makers don’t say how often their microdeletion tests are being performed.

But it is clear some of the tests are in widespread use. One large test maker, Natera, said that in 2020 it performed more than 400,000 screenings for one microdeletion — the equivalent of testing roughly 10 percent of pregnant women in America.

To evaluate the newer tests, The Times interviewed researchers and then combined data from multiple studies to produce the best estimates available of how well the five most common microdeletion tests perform.

The analysis showed that positive results on those tests are incorrect about 85 percent of the time.

Experts say there is no single threshold for how often a test needs to get positive results right to be worth offering. They note that when the tests do accurately identify an abnormality, it can give expectant parents time to learn about and prepare for challenges to come. Some said one common microdeletion screening, for a condition called DiGeorge syndrome, has the most potential to do good.

But there are hundreds of microdeletion syndromes, and the most expansive tests look for between five and seven, meaning women shouldn’t take a negative result as proof their baby doesn’t have a genetic disorder. For patients who are especially worried, obstetricians who study these screenings currently recommend other types of testing, which come with a small risk of miscarriage but are more reliable.

Some said the blood screenings that look for the rarest conditions are good for little more than bolstering testing companies’ bottom lines.

“It’s a little like running mammograms on kids,” said Mary Norton, an obstetrician and geneticist at the University of California, San Francisco. “The chance of breast cancer is so low, so why are you doing it? I think it’s purely a marketing thing.”

There are few restrictions on what test makers can offer. The Food and Drug Administration often requires evaluations of how frequently other consequential medical tests are right and whether shortfalls are clearly explained to patients and doctors. But the F.D.A. does not regulate this type of test.

Alberto Gutierrez, the former director of the F.D.A. office that oversees many medical tests, reviewed marketing materials from three testing companies and described them as “problematic.”

“I think the information they provide is misleading,” he said.

Patients who receive a positive result are supposed to pursue follow-up testing, which often requires a drawing of amniotic fluid or a sample of placental tissue. Those tests can cost thousands of dollars, come with a small risk of miscarriage and can’t be performed until later in pregnancy — in some states, past the point where abortions are legal.

The companies have known for years that the follow-up testing doesn’t always happen. A 2014 study found that 6 percent of patients who screened positive obtained an abortion without getting another test to confirm the result. That same year The Boston Globe quoted a doctor describing three terminations following unconfirmed positive results.

Three geneticists recounted more recent examples in interviews with The Times. One described a case in which the follow-up testing revealed the fetus was healthy. But by the time the results came, the patient had already ended her pregnancy.

After being presented with some of The Times’s reporting, half a dozen of the largest prenatal testing companies declined interview requests. They issued written statements that said patients should always review results with a doctor, and cautioned that the tests are meant not to diagnose a condition but rather to identify high-risk patients in need of additional testing.

In interviews, 14 patients who got false positives said the experience was agonizing. They recalled frantically researching conditions they’d never heard of, followed by sleepless nights and days hiding their bulging bellies from friends. Eight said they never received any information about the possibility of a false positive, and five recalled that their doctor treated the test results as definitive.

When Meredith Bannon’s pregnancy tested positive for DiGeorge syndrome, a nurse called and told her she and her husband would soon face “tough decisions” related to their child’s “quality of life,” which Ms. Bannon took to mean a choice about whether to end the pregnancy.

The call came as Ms. Bannon was driving to her parents’ house, with her son in the back seat wearing a “big brother” T-shirt. “I was coming home to tell them that I was pregnant, but instead I had to tell them the news I got this horrible result back,” Ms. Bannon recalled.

Further testing revealed that the result was wrong. Her baby is due in April.

Some women began tentatively planning abortions after receiving positive screenings.