What is noninvasive prenatal testing (NIPT) and what disorders can it screen for?
Noninvasive prenatal testing (NIPT) analyzes cell-free DNA in a pregnant woman's blood to estimate the risk of fetal chromosomal abnormalities without posing a risk to the fetus.
How NIPT Works
Noninvasive prenatal testing (NIPT), also known as noninvasive prenatal screening (NIPS), analyzes small fragments of DNA circulating in a pregnant woman’s blood. Unlike DNA found in a cell's nucleus, these fragments are free-floating and are called cell-free DNA (cfDNA). These fragments typically arise when cells die and break down, releasing their contents into the bloodstream.
During pregnancy, the mother’s blood contains a mix of cfDNA from her own cells and from the placenta. Because placental cells are shed into the maternal bloodstream and their DNA is usually identical to that of the fetus, analyzing this cfDNA allows for early detection of certain genetic abnormalities without harming the fetus.
What NIPT Screens For
NIPT is primarily used to identify chromosomal disorders caused by an extra or missing copy of a chromosome (aneuploidy). These include:
- Down syndrome (trisomy 21)
- Trisomy 18
- Trisomy 13
- Extra or missing copies of the X and Y chromosomes (sex chromosomes)
The test may also screen for chromosomal disorders caused by missing (deleted) or copied (duplicated) sections of a chromosome, and it is increasingly being used to test for single-gene disorders.
Understanding Results and Limitations
NIPT is a screening test, not a diagnostic test. It provides an estimate of risk rather than a definitive answer. Results can sometimes indicate an increased risk when the fetus is unaffected (false positive) or a decreased risk when the fetus is actually affected (false negative). Because the test analyzes both maternal and fetal cfDNA, it may also detect genetic conditions in the mother.
The Importance of Fetal Fraction
For the test to be effective, there must be a sufficient amount of fetal cfDNA in the mother’s blood, known as the fetal fraction. This must generally be above 4 percent, which typically occurs around the tenth week of pregnancy. Factors such as testing too early, maternal obesity, sampling errors, or fetal abnormality can lead to low fetal fractions, which may result in an inability to perform the test or a false negative result.
Interpreting the Data
The most common method for determining chromosomal aneuploidy involves counting all cfDNA fragments. If the percentage of fragments from a specific chromosome is higher than expected, it indicates an increased likelihood of a trisomy condition (a positive result). A positive screening result indicates that further diagnostic testing should be performed to confirm the findings.