Some of the tests look for missing parts of the chromosomes. They find a problem every 15 times.
They are incorrect 85 times.
Sarah Kliff and Aatish Bhatia.
January 1, 2022.
Yael was thrilled when she found out she was pregnant in November 2020. She was confident enough to tell her 3-year-old son that his brother or sister was in her belly.
She was called by her doctor's office as she drove her son home from school. A pregnant woman had a blood test that showed her fetus might be missing a part of a chromosomes.
She cried as she explained to her husband that they might be facing a decision on whether or not to end the pregnancy. He sat quietly. How is this happening to me? Ms. Geller recalled thinking.
Doctors used a long, painful needle to get a small piece of her body. The initial result was wrong when it was tested. She has a baby who shows no signs of the condition he was screened positive for.
The image is.
The New York Times has a story about Yael and her son.
Silicon Valley promised expectant mothers that a small amount of their blood drawn in the first trimester could be used to detect serious developmental problems in 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.
The tests initially looked for Down syndrome. As manufacturers tried to outsell each other, they began offering additional screenings for rare conditions.
The New York Times found that grave predictions made by those newer tests are usually wrong.
The screening that came back positive for Ms. Geller looked for Prader-Willi syndrome, a condition that offers little chance of living independently as an adult. Positive results are incorrect more than 90 percent of the time.
The tests are described to pregnant women and their doctors as near certain on the product brochure and test result sheets. They claim their findings are reliable and accurate, and that they offer total confidence and peace of mind for patients who want to know as much as possible.
Some of the companies offer tests without publishing data on how well they perform, or point to numbers for their best screenings, while leaving out weaker ones. Some people base their claims on studies in which only one or two pregnancies actually have the condition.
Silicon Valley firms have tried to build businesses around blood tests. The 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.
The science behind these companies' ability to test blood for disorders is not in question. It has changed the way Down syndrome screening is done.
When it looks for less common conditions, the same technology performs much worse. Small missing pieces of chromosomes are the cause of most of the problems. Some stem from missing or extra copies of chromosomes. Intellectual disability, heart defects, and a high infant mortality rate are some of the symptoms they can have.
Microdeletion testing is an optional add-on to the Down screening, and it is not every patient that is screened for every condition. Most test makers don't say how often their tests are done.
The Upshot Newsletter Analysis explains politics, policy and everyday life with an emphasis on data and charts. It will be sent to your inbox.
Some of the tests are being used. Roughly 10 percent of pregnant women in America are tested for one microdeletion, according to one large test maker.
To evaluate the newer tests, The Times interviewed researchers and then combined data from multiple studies to produce the best estimates of how well the five most common microdeletion tests perform.
Positive results on those tests are incorrect about 85% of the time.
More of the positive results are incorrect as the tests have expanded to more rare conditions. Microdeletions are small missing snippets of chromosomes and are some of the worst-performing tests.
There is a chance that it is positive.
The results are not correct.
It affects 1 in 4,000 births.
Delayed language acquisition can cause heart defects. May appear on lab reports.
1 in 5,000 births.
Can cause intellectual disability.
1 in 15,000 births.
Difficult walking and delayed speech development can be caused by this.
1 in 20,000 births.
Growth delays and intellectual disability can be caused by this.
1 in 20,000 births.
It can cause seizures and make it hard to control food consumption.
Testing companies offer seven screenings. There isn't enough data to understand how well the tests work for two syndromes. There are a few other tests for conditions that are not caused by microdeletions. The screenings for Patau syndrome and Turner syndrome generate a large percentage of incorrect positives, while the screenings for Down syndrome and Edwards syndrome work well.
The figures are pooled from multiple studies. The estimate for Wolf-Hirschhorn syndrome is based on limited data.
There isn't a single threshold for how often a test needs to get positive results to be worth offering. When the tests accurately identify an abnormality, it can give expectant parents time to learn about and prepare for challenges to come. One common screening for a condition called DiGeorge syndrome has the most potential to do good, according to some.
The most expansive tests look for between five and seven syndromes, meaning that women shouldn't take a negative result if their baby doesn't have a genetic disorder. Obstetricians who study these screenings recommend other types of testing, which come with a small risk of miscarriage but are more reliable, for patients who are especially worried.
Some people said the blood screenings that look for the rare conditions are not very useful.
MaryNorton, an otosclerosis and geneticist at the University of California, San Francisco, said that it was like running mammograms on kids. The chance of breast cancer is low so why are you doing it? I think it is a marketing thing.
There are no restrictions on what test makers can offer. The Food and Drug Administration requires evaluations of how frequently other consequential medical tests are right and whether shortfalls are clearly explained to patients and doctors. The F.D.A. doesn't regulate this type of test.
The former director of the F.D.A. office reviewed marketing materials from three testing companies and described them as problematic.
He said the information they give is misleading.
A sample ofamniotic fluid or a sample of placental tissue is required for follow-up testing for patients who receive a positive result. Those tests can cost thousands of dollars, come with a small risk of a baby being born with no heartbeat, and can't be performed until later in the pregnancy, in some states.
The companies have known for a long time that follow-up testing isn't always done. A study found that 6 percent of patients who screened positive got an abortion without a second test. The Boston Globe quoted a doctor who said he terminated three patients after positive results.
Three geneticists spoke to The Times. The case in which the fetus was found to be healthy was described by one. The patient ended her pregnancy before the results came.
Half a dozen of the largest prenatal testing companies declined interview requests after being presented with some of The Times reporting. They warned patients that the tests are not meant to diagnose a condition but to identify high-risk patients in need of additional testing.
Fourteen patients who got false positives said the experience was very difficult. They hid their bulging bellies and sleepless nights from their friends. Eight people said they didn't know about the possibility of a false positive, and five said their doctor treated the test results as conclusive.
The nurse told the couple that they would face tough decisions about their child's quality of life after the baby was born.
The call came as Ms. Bannon was driving with her son in the back of the car. I had to tell them that I was pregnant, but they didn't know that I got a horrible result.
The result was wrong. The baby is due in April.
Some women began planning abortions after receiving positive screenings.
The image is.
Allison Mihalich lives in St. Pete, Fla. She had a test that indicated a problem.
Allison Mihalich, 33, had to have her baby terminated because of a screening error that indicated her baby might have Turner syndrome, which can cause infertility and heart defects. Studies show that the test results are wrong 74 percent of the time. She was in Indiana at the time and had to arrange follow-up testing before the state banned abortion after 22 weeks.
Sequenom, a small Silicon Valley-based company, tripled in size over the course of two years. The key to its success was the new screening test, MaterniT21, which did well at detecting Down syndrome.
Multiple blood tests were required for older screening tests. There were fewer false positives with this new one.
The sex of a fetus could be determined by the test. It became a hit. Dr. Anjali Kaimal, a maternal-fetal medicine specialist at Massachusetts General Hospital, said that people were walking in requesting a sex test.
Competitors began to conduct their own tests. The number of women taking these tests is expected to double by the year 2025.
Many companies decided to start screening for more and rarer disorders as they began looking for ways to differentiate their products. All the screenings could be done on the same blood draw, and doctors already order many tests during short prenatal care visits, meaning some probably thought little of tacking on a few more.
Adding microdeletions can double what an insurer pays for the basic tests, according to the health data company Concert Genetics. Patients with insurance that didn't fully cover the tests are being billed wildly different figures.
There were few instances for the tests to find these conditions.
In 2020, 400,000 tests were run for DiGeorge syndrome, a disorder associated with heart defects and intellectual disability.
After The Times presented its reporting, Natera declined an interview request. It said that the early detection of DiGeorge syndrome can improve patient outcomes, and that it rarely identifies other conditions. Positive results from the screening that wrongly diagnosed Ms. Geller's pregnancy with Prader-Willi syndrome only returned 114 times since 2015. It pointed to a recent study that found the condition to occur in 1 in 1,600 births, twice as common as other estimates.
The company offers free genetic counseling to patients who screen positive. The data on how often positive results are right is published by the company.
Other companies don't give much information about how many tests they sell or how well their screenings work.
Even though the study on the test includes just two confirmed cases of microdeletions, the Prequel test still offers five microdeletion screenings.
In a statement, the company estimated that only one in 9000 of its patients had a microdeletion. The data showed that a small percentage of those are wrong.
There are few known examples of companies testing for rare conditions.
One of the disorders that Labcorp and Myriad Genetics offer screenings for is so rare it is unknown, and another is called Jacobsen syndrome, which affects 1 in 100,000 births.
Dr. Diana Bianchi runs a laboratory that screens pregnant women. She said that she had never seen a case of Jacobsen syndrome in her 20 years of practicing genetics.
Estimates are based on a test.
When companies explain the tests to doctors, they rarely mention the shortfalls.
Even though most studies show that the test is usually wrong, a Labcorp report tells patients that the test detected a problem. On its website, Myriad Genetics said it had total confidence in every result, but it didn't say how often false positives occur.
The language was taken down after The Times inquired.
The Times reviewed 17 patient and doctor brochures from the testing companies. A false positive can happen, but not in all of the brochures. One mentioned how often the tests get positive results wrong.
There are examples of positive things.
The results of the test.
There are tests for these conditions.
Positives are usually wrong.
The high probability is defined in a footnote.
as 1% or greater.
There are examples of positive things.
The results of the test.
There are tests for these conditions.
Positives are usually wrong.
The high probability is defined in a footnote.
as 1% or greater.
Some doctors may not understand how bad the tests are. Patients may still be inclined to believe the results sheets even if caregivers do not interpret them correctly.
When Cloey Canida got a positive result from the Harmony test, the result sheet said her daughter had a high chance of being born with Patau syndrome, a condition that babies often do not survive beyond a week.
Independent data shows that 93 percent of positives for a woman her age turn out to be wrong.
Ms. Canida was thinking about the result sheet. She remembers crying during the abortion and thinking she would see her child move.
She found out that her daughter would not be born with Patau syndrome after spending $1,200 on follow-up tests. She is in her third trimester.
The image is.
Cloey Canida is near her home in Tuolumne, Calif.
She said that she would have liked to have been aware of the false positive rate before agreeing to the test. I was not given any information about that.
All women should discuss their results with their health care provider before making any decisions based on screening results, according to a statement from the company.
Three experts reviewed marketing materials and results sheets for The Times and identified obvious reasons a patient would be confused.
The former F.D.A. official said that the numbers were meaningless.
The test is supposed to get positive results 75 percent of the time. The figure comes from a single study that included nine confirmed cases of microdeletions. The company didn't specify how the tests perform individually, and didn't give that data. In a statement, the company said its test had excellent performance.
The F.D.A. contemplated regulating these tests a decade ago. If the agency had oversight, it would be required to publish a brochure, but it would not look like this.
Microdeletions are viewed as a major business opportunity by companies if they can persuade more doctors to order them and more insurers to cover them.
The Prequel test is owned by Myriad Genetics and it has told investors that it will lobby the professional society for obstetricians to recommend the test to their members.
More than two million screenings for Down syndrome have been performed by the company. The value of its stock has grown to almost $9 billion after it went public.
The company sees more growth with its expanded panel of screenings. Steve Chapman, the company's chief executive, said at an investor conference last January that this is a significant moment for the microdeletions business.
The company had revenues of $391 million in 2020 and projected revenues of $615 million in 2021. It could bring in up to another $300 million a year if more insurers start paying for the tests.
Kitty Bennett was involved in research.
About the analysis.
To estimate the performance of screening tests, The Times interviewed genetic counselors and experts on medical testing and prenatal care, then searched for peer-reviewed studies of screenings by U.S.-based labs that included follow-up diagnostic testing. Three of the studies were funded by one of the test makers. Results from a recent clinical trial of its microdeletion test were included in an additional report by Natera. Experts identified multiple problems with the study's methodology, so it was excluded. Reporters combined the data from the studies and came up with a positive predictive value of 15 percent. Two researchers looked at the analysis.
Projections of performance numbers are included in three of the four Natera studies and are based on re-analyzing the blood samples they collected with a modified version of the original test. Some experts warned that this technique can inflate a test's performance, while others said it was a common practice that helped improve results over time. The company could not duplicate those projections in subsequent studies. The Times used higher projected numbers in its estimates and used clinical data instead to decrease the test's positive predictive value.
