Date Issued: April 19, 2022
The U.S. Food and Drug Administration (FDA) is warning patients and health care providers about the risks of false results with genetic non-invasive prenatal screening (NIPS) tests, sometimes called noninvasive prenatal testing or tests (NIPT). Results from NIPS tests can provide information about the possibility of a fetus having certain genetic abnormalities that could result in a child being born with a serious health condition.
While health care providers widely use NIPS tests, none have yet been authorized, cleared, or approved by the FDA. The accuracy and performance of NIPS tests have not been evaluated by the FDA and these tests can give false results, such as reporting a genetic abnormality when the fetus does not actually have one. NIPS tests are screening tests, which means the NIPS test may only tell you the risk of the fetus having certain genetic abnormalities. They are not diagnostic tests, which are generally used to more definitively confirm or rule out a suspected genetic abnormality.
The FDA is aware of reports that patients and health care providers have made critical health care decisions based on results from these screening tests alone and without additional confirmatory testing. Specifically, pregnant people have ended pregnancies based only on the results of NIPS tests. 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 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.
Given the increased use of these tests and concerns raised in recent media reports, the FDA is providing this information to educate patients and health care providers and to help reduce the inappropriate use of NIPS tests. The FDA recommends that patients discuss the benefits and risks of NIPS tests with a genetic counselor or other health care provider before deciding to get these tests. Patients should also discuss the results of NIPS tests with a genetic counselor or other health care provider before making any decisions about their pregnancy. Health care providers should be aware of the risks and limitations of using these screening tests and should not use the results from these tests alone to diagnose chromosomal (genetic) abnormalities or disorders.
Recommendations for Patients
- Talk with a genetic counselor or other health care provider before deciding to have prenatal testing and to discuss which tests to use, including genetic screening tests such as NIPS tests. Genetic counselors and other health care providers can help you understand the benefits and risks of these tests.
- Do not use the results of screening tests such as NIPS tests alone to make decisions about your pregnancy because the results of these tests may not accurately reflect whether your fetus has a genetic abnormality. Additional testing may require invasive procedures to obtain a sample, such as amniocentesis or chorionic villous sampling (CVS), which carry a small risk of miscarriage. The diagnostic confirmatory tests performed on these samples may not have been reviewed by the FDA.
- Discuss the results of genetic prenatal screening tests and what the results may mean with a genetic counselor or other health care provider. They can help you decide whether to get additional testing to confirm results from a screening test.
- A positive screening test result means that the fetus has a higher risk of having a genetic abnormality compared with the average risk. It does not mean that the fetus definitively has a genetic abnormality, or a condition caused by a genetic abnormality.
- A negative screening test result means that the fetus has a lower risk of having a genetic abnormality compared with the average risk. It does not rule out the possibility that the fetus has a genetic abnormality, or a condition caused by a genetic abnormality.
- The ability of a NIPS test to correctly tell whether a fetus is at risk for a genetic abnormality depends on how common or rare the genetic abnormality is and on underlying risk factors. Disorders caused by a microdeletion (small missing piece of a chromosome) are rare. Because these conditions are so rare, a positive result may be more likely to be from a healthy fetus than one that actually has the reported genetic abnormality.
Recommendations for Health Care Providers
- Review the Recommendations for Patients with your pregnant patients.
- In addition to technical issues, multiple biological factors can influence NIPS results. For example, in some cases, a positive NIPS test result may accurately detect a chromosomal abnormality, but that abnormality is in the placenta and not in the fetus. In these cases, the fetus may be healthy. Additional confirmatory diagnostic tests should be performed to determine whether or not the fetus is affected.
- Discuss with your patients the benefits and risks of prenatal tests, including genetic screening tests such as NIPS tests.
- Do not use the results of screening tests such as NIPS tests alone to diagnose chromosomal abnormalities or disorders.
- Ensure your patients receive the appropriate follow-up testing and care, including genetic counseling, as needed.
Test Description and Background
Noninvasive prenatal screening (NIPS) tests analyze small fragments of fetal DNA, called cell-free DNA, that are circulating in a pregnant person’s blood with the goal of determining the risk that the fetus has certain genetic abnormalities. When used appropriately, these tests offer a non-invasive approach for prenatal screening and may provide useful information to assess the risk that a fetus has (or does not have) a genetic abnormality. It is important for patients and health care providers to be aware that these are screening tests, not diagnostic tests, and to understand the benefits, risks, and limitations of these tests.
Many laboratories that offer these tests claim the tests are “reliable” and “highly accurate,” offering “peace of mind” for patients. The FDA is concerned that these claims may not be supported with sound scientific evidence. False claims may cause patients as well as health care providers to believe the test results are reliable and can be used alone to make decisions about the pregnancy. In addition, because some of the genetic abnormalities and disorders are so rare, in cases such as detection of a microdeletion, there may be a high chance that a positive result is actually from a fetus that does not have the genetic abnormality reported by the test.
The NIPS tests currently being offered are marketed as laboratory developed tests (LDTs). Most LDTs, including NIPS tests, are offered without FDA review. While LDTs are medical devices under the Federal Food, Drug, and Cosmetic Act, the FDA has had a general policy of enforcement discretion for most LDTs since the Medical Device Amendments were enacted in 1976. That means that FDA does not generally enforce applicable regulatory requirements for most LDTs. The FDA is continuing to work with Congress on legislation to establish a modern regulatory framework for all tests, including LDTs.
Additional Information for Health Care Providers
The FDA recommends that health care providers also be aware of the positions of relevant professional societies, including the American College of Obstetricians and Gynecologists (ACOG), the Society for Maternal-Fetal Medicine (SMFM), and the American College of Medical Genetics and Genomics (ACMG):
- These medical professional societies recommend that prenatal genetic screening should be discussed and offered to all patients regardless of their age or risk for a chromosomal abnormality.
- Patient education is emphasized in order to support informed decision making about whether to accept or decline screening. Emphasis is placed on education surrounding the positive predictive value of NIPS tests and the appropriate use of cell-free DNA tests as screening and not diagnostic tests.
- ACMG specifically recommends against testing for aneuploidies (missing or extra chromosomes) other than those involving chromosomes related to Down syndrome (21), Edwards syndrome (18) and Patau syndrome (13).
- ACOG does not recommend the use of NIPS tests to detect microdeletions.
Published studies also strongly support the importance of performing confirmatory diagnostic testing to determine whether or not the fetus truly has a chromosomal abnormality following a positive screening test result. The scientific literature related to the use of NIPS tests from laboratories, including 25 peer-reviewed publications covering 13 studies evaluating more than 10,000 individuals undergoing NIPS, indicates that the NIPS tests evaluated generally perform well for ruling out disorders caused by chromosomal abnormalities. The scientific literature generally report high negative predictive values, greater than 99.9% when calculated, for the NIPS tests studied. This means that the fetus is very likely not to have a chromosomal abnormality if the test returns a negative result. However, the literature confirms that the reliability of positive screening results is limited, particularly for microdeletions. Reliability of positive screening results in these studies was best for Down syndrome, with a positive predictive value of about 90%, meaning that one in 10 positive results are not confirmed as Down syndrome. However, reliability of positive screening results was far lower for microdeletions, with the positive predictive value ranging from about 2% to 30%, depending on the condition. For example, Di George syndrome, which is caused by a microdeletion on chromosome 22, showed a positive predictive value of about 30%. This means that, out of 10 patients receiving a positive result for Di George syndrome on a screening test, it is not confirmed in 7 of those patients when diagnostic testing is performed with CVS or amniocentesis.
The FDA is informing the public of the risks related to the use of genetic prenatal screening and the potential harm if NIPS test results are not used and interpreted appropriately.
The FDA encourages test developers 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. The FDA also encourages test developers to work with the FDA toward authorization, clearance, or approval of their tests.
The FDA will continue to closely monitor safety issues around the use of NIPS tests and is committed to protecting public health. The FDA will keep the public informed if significant new information becomes available.
Reporting Problems with Your Device
If you think you had a problem with a non-invasive prenatal screening (NIPS) test, the FDA encourages you to report the problem through the MedWatch Voluntary Reporting Form.
Health care personnel employed by facilities that are subject to the FDA’s user facility reporting requirements should follow the reporting procedures established by their facilities.
If you have questions, email the Division of Industry and Consumer Education (DICE) at [email protected] or call 800-638-2041 or 301-796-7100.