FDA warns against relying on genetic screening tests to make prenatal diagnoses

The current genetic testing development boom has undeniably advanced the medical field by leaps and bounds—but that doesn’t mean every test’s results should be automatically taken as gospel.

That’s the gist of a safety communication the FDA published this week. The agency warns that although many healthcare providers have gotten into the habit of performing genetic noninvasive prenatal screening (NIPS) tests, none of them have yet been cleared or approved by the FDA to provide firm diagnoses and “may be making claims about their performance and use that are not based on sound science,” according to Jeff Shuren, M.D., director of the FDA’s Center for Devices and Radiological Health.

NIPS tests work by analyzing tiny pieces of fetal DNA found in a pregnant person’s bloodstream. Most are offered as lab-developed tests—which don’t require FDA review—and screen for genetic conditions like Down syndrome and DiGeorge syndrome.

The NIPS tests’ “screening” specification means that they can only calculate the risk that a fetus has certain genetic abnormalities, rather than definitively confirming or ruling out those mutations, according to the FDA, which also warned that those risk calculations may be wrong, since it has yet to assess the accuracy and performance of any NIPS tests.

Studies of the tests’ performance shows that while they’re more than 99.9% accurate at ruling out genetic conditions, their accuracy severely drops off when it comes to confirming the presence of a mutation—especially when it comes to very rare conditions—with high rates of false positives.

The FDA noted that if a false-positive NIPS test result is used as a hard and fast diagnosis, it could lead to inappropriate and invasive medical procedures and even the unnecessary termination of a pregnancy.

“Without confirming the results with a diagnostic test, there is no way to know whether the fetus actually had the genetic abnormality reported by the screening test,” the agency wrote. “The FDA is aware of cases where a screening test reported a genetic abnormality, and a confirmatory diagnostic test later found that the fetus was healthy.”

Other inaccurate results may stem from technical issues, per the FDA, such as when a chromosomal abnormality is correctly detected in cell-free DNA, but that DNA comes from the placenta rather than the fetus itself.

To avoid such situations, the FDA recommends that healthcare providers ensure their patients understand that NIPS tests only offer a rough idea of the possibility that a genetic condition is present. Additionally, any findings from those screening tests should be confirmed with FDA-authorized diagnostics before any other medical actions are taken.

“Without proper understanding of how these tests should be used, people may make inappropriate healthcare decisions regarding their pregnancy,” Shuren said. “We strongly urge patients to discuss the benefits and risks of these tests with a genetic counselor or other healthcare provider prior to making decisions based on the results of these tests.”

As for the tests’ makers, the agency encouraged them to “provide accurate, clear and complete information about the performance of their tests, how they should be used and what the results may or may not mean” and to consider working with the FDA to secure official authorization of their tests.