Prenatal cell-free DNA screening (NIPT): what it checks and what results mean
Cell-free DNA screening, also called NIPT or NIPS, is a blood test in pregnancy that estimates whether the fetus is at higher or lower risk of certain conditions caused by an abnormal number of chromosomes. It is a screening test, so it cannot say for sure whether the fetus has a condition. (MedlinePlus Genetics) (MedlinePlus, cfDNA test)
What it checks
During pregnancy, the blood contains small pieces of DNA that float free of cells. Some come from the pregnant person and some from the placenta, whose DNA is usually identical to the fetus's. (MedlinePlus Genetics) The test looks for an abnormal amount of DNA from chromosomes 21, 18 and 13. (ACOG/NSGC/SMFM)
- Main conditions: Down syndrome (trisomy 21), Edwards syndrome (trisomy 18) and Patau syndrome (trisomy 13), plus problems with the number of sex chromosomes. (ACOG FAQ165)
- Accuracy varies by condition. Some tests also look for missing or extra pieces of chromosomes. (MedlinePlus Genetics)
- Not screened for: problems found by ultrasound, such as neural tube defects, heart defects and abdominal wall defects, and many other chromosomal and genetic disorders. (ACOG/NSGC/SMFM)
- Findings about the pregnant person: because the test reads DNA from both the pregnant person and the placenta, it may detect a genetic condition in the mother. (MedlinePlus Genetics)
Who is offered it, and when
ACOG and SMFM say each patient should be counseled in each pregnancy about options for testing for fetal chromosomal abnormalities, that all patients should be offered both screening and diagnostic tests, and that all patients have the right to accept or decline testing after counseling. Their 2020 Practice Bulletin covers the use of cell-free DNA in all patients regardless of maternal age or baseline risk. (ACOG/SMFM PB 226, 2020)
The test can be done from 10 weeks of pregnancy until delivery. (ACOG/NSGC/SMFM) Results take about 1 week. (ACOG FAQ165) It is a blood draw from a vein in the arm, with no risk to the baby. MedlinePlus suggests you may want to speak to a genetic counselor before testing. (MedlinePlus, cfDNA test)
How it compares with other screening tests
| Test | When | What it screens for |
|---|---|---|
| First-trimester screening | Usually 10 to 13 weeks | A blood test that measures two substances, plus an ultrasound (nuchal translucency) that measures a space at the back of the fetus's neck. Screens for Down syndrome (trisomy 21) and other aneuploidy. (ACOG FAQ165) |
| Quad (quadruple) blood test | 15 to 22 weeks | Measures four substances in the pregnant person's blood. Screens for Down syndrome, Edwards syndrome (trisomy 18) and neural tube defects. (ACOG FAQ165) |
| Combined first- and second-trimester screening | Final results often not until the second trimester | Combines results from the first- and second-trimester tests; combined results are more accurate than a single test result. (ACOG FAQ165) |
| Cell-free DNA screening (NIPT) | From 10 weeks until delivery; results in about 1 week | DNA from the placenta in the pregnant person's blood. Screens for Down syndrome, Edwards syndrome, Patau syndrome (trisomy 13) and problems with the number of sex chromosomes. (ACOG FAQ165) (ACOG/NSGC/SMFM) |
The ACMG 2022 guideline found that cell-free DNA screening was more accurate than traditional screening methods for trisomies 21, 18 and 13 in single and twin pregnancies. (ACMG, 2022) ACOG and SMFM say no one screening test is superior in all circumstances. (ACOG/SMFM PB 226, 2020)
What the results mean
| Result | What it means |
|---|---|
| Negative (low risk) | The fetus is at lower risk of the disorder than the general population. It does not rule out the disorder, or other conditions the test does not check for. (ACOG FAQ165) (ACOG/NSGC/SMFM) |
| Positive (high risk) | The fetus is at higher risk of the disorder than the general population. It does not mean the fetus definitely has it; a diagnostic test (CVS or amniocentesis) is needed to find out if the fetus is truly affected. (ACOG FAQ165) (ACOG/NSGC/SMFM) |
| No result or indeterminate | Sometimes the test does not give a result. Further genetic counseling is advised, and an ultrasound exam and diagnostic testing should be offered, because of an increased risk of a chromosomal disorder. (ACOG/NSGC/SMFM) |
Why a high-risk result is not a diagnosis
The positive predictive value (PPV) is how likely it is that the fetus has the condition after a positive result. For cell-free DNA screening, it depends on how often the condition occurs in a group of people similar to you. ACOG, NSGC and SMFM give this example for Down syndrome: (ACOG/NSGC/SMFM)
- Higher-risk group: PPV 83%. Out of 100 women with a positive result, 83 will have babies with Down syndrome and 17 will not.
- Lower-risk group: PPV 33%. Out of 100 women with a positive result, 33 will have babies with Down syndrome and 67 will not.
- Negative result: negative predictive value above 99% in both groups; women with a negative result will only rarely have a baby with Down syndrome.
In that example, the higher-risk group includes people who are 35 or older, have had an ultrasound showing a possible problem with the fetus, have had a previous child with one of these disorders, have a chromosomal problem that raises the risk of trisomy 21 or 13, or have had a positive first- or second-trimester screening result. (ACOG/NSGC/SMFM)
Results can be falsely high-risk when the fetus is unaffected, or falsely low-risk when it is affected. A low share of placental DNA (the fetal fraction) can lead to no result or to a false negative. (MedlinePlus Genetics) More on how this happens with any screening test: false positives and overdiagnosis.
Diagnostic tests that confirm a result
- Chorionic villus sampling (CVS): collects tissue from the placenta, whose cells usually have the same chromosomes as the baby. It may be done between weeks 10 and 13. (MedlinePlus, cfDNA test)
- Amniocentesis: takes a sample of the fluid around the baby, which contains cells from the baby. It is usually done between weeks 15 and 20. (MedlinePlus, cfDNA test)
- MedlinePlus says these are usually very safe procedures but have a slight risk of causing a miscarriage. (MedlinePlus, cfDNA test) ACOG says diagnostic testing is an option for all pregnant women, and an obstetrician or genetic counselor will discuss what screening results mean. (ACOG FAQ165)
Where they differ:
- ACOG and SMFM (US, 2020): offer screening and diagnostic testing to all patients; the bulletin covers cell-free DNA for all patients regardless of age or baseline risk, and says no one screening test is best in all circumstances. (ACOG/SMFM PB 226, 2020)
- ACMG (US, 2022): strongly recommends cell-free DNA screening over traditional screening for all patients with single or twin pregnancies for trisomies 21, 18 and 13, and that it be offered to screen for sex chromosome conditions. (ACMG, 2022)
- NHS England and NICE (England): NICE says to offer the NHS fetal anomaly screening programme, with a scan between 11+2 and 14+1 weeks that, if chosen, screens for Down's, Edwards' and Patau's syndromes. (NICE NG201) The programme names the first-trimester combined test as the test of choice and offers NIPT only after a higher chance result (between 1 in 2 and 1 in 150) from the combined or quadruple test. (NHS FASP)
- Twins: MedlinePlus says cell-free DNA screening is less accurate with more than one baby (MedlinePlus, cfDNA test), while ACMG recommends it for twin pregnancies too. (ACMG, 2022)
Your doctor decides what your result means for you.
This page does not give treatment advice or advice about decisions in your pregnancy. If you have an abnormal result, see after an abnormal screening result for questions to ask.
Questions people ask
Who is offered cell-free DNA screening?
ACOG and SMFM say every pregnant patient should be counseled in each pregnancy about options for testing for fetal chromosomal abnormalities, and that all patients should be offered both screening and diagnostic tests. Their 2020 Practice Bulletin expanded information on the use of cell-free DNA in all patients regardless of maternal age or baseline risk. Testing is the patient's choice. (ACOG/SMFM PB 226, 2020)
How early can NIPT be done?
ACOG says a cell-free DNA test can be done as early as 10 weeks of pregnancy and up until delivery, and it takes about 1 week to get the results. MedlinePlus Genetics explains that there must be enough DNA from the placenta in the blood, which typically happens around the tenth week. (ACOG/NSGC/SMFM) (ACOG FAQ165) (MedlinePlus Genetics)
Is a positive NIPT result a diagnosis?
No. It means a higher risk, not a certain answer. ACOG says a positive cell-free DNA result should be followed by a diagnostic test with amniocentesis or CVS. (ACOG FAQ165)
Why did my NIPT not give a result?
MedlinePlus Genetics says a low share of placental DNA in the blood (the fetal fraction) can make the test impossible to perform. Reasons include testing too early, sampling errors, maternal obesity and fetal abnormality. ACOG, NSGC and SMFM say that after no result, genetic counseling, an ultrasound and diagnostic testing should be offered. (MedlinePlus Genetics) (ACOG/NSGC/SMFM)
Does NIPT check for everything?
No. ACOG says it does not screen for problems found by ultrasound, such as neural tube defects, heart defects and abdominal wall defects, or for many other chromosomal and genetic disorders. If you have cell-free DNA screening, a blood test or ultrasound should be offered to screen for neural tube defects and other conditions. (ACOG/NSGC/SMFM)
Does NIPT work with twins?
MedlinePlus says cell-free DNA screening is not as accurate with more than one baby. The ACMG 2022 guideline recommends it for both singleton and twin pregnancies for trisomies 21, 18 and 13. (MedlinePlus, cfDNA test) (ACMG, 2022)