During pregnancy, a small amount of genetic material passes from the placenta into the mother’s bloodstream. This material is known as cell-free DNA (cfDNA), and the proportion that comes specifically from the placenta is called the fetal fraction. This measurement is a central component of non-invasive prenatal testing (NIPT), a screening method used to assess the likelihood of certain genetic conditions.
Expressed as a percentage, fetal fraction represents the amount of placental DNA compared to the total cfDNA in the maternal blood sample. This placental DNA is genetically identical to that of the fetus, providing a way to screen for specific chromosomal differences without invasive procedures.
The Role of Fetal Fraction in Test Accuracy
The measurement of fetal fraction serves as a quality check for the NIPT sample. For a laboratory to provide a reliable analysis, there must be a sufficient amount of fetal DNA to detect. Think of it as a radio signal: the fetal cfDNA is the “signal,” and the much larger amount of maternal cfDNA is the “static.” A weak signal makes the broadcast unclear.
A higher fetal fraction percentage means there is a stronger, more distinct signal from the placenta’s DNA. With a robust sample, the laboratory can more easily distinguish between the fetal and maternal DNA fragments, leading to a more confident and accurate analysis.
Conversely, if the fetal fraction is too low, the signal is too faint to be accurately analyzed. Most laboratories have a minimum threshold, often between 2% and 4%, required to run the test. If the sample falls below this cutoff, the lab cannot provide a conclusive result.
Factors Influencing Fetal Fraction Levels
Several biological factors can influence the percentage of fetal fraction. One of the most significant is gestational age, as the fetal fraction increases as the pregnancy progresses. A blood sample taken earlier in the pregnancy, particularly before the tenth week, is more likely to have a lower percentage.
A person’s body mass index (BMI) also plays a part. Individuals with a higher BMI tend to have a larger overall blood volume and a higher concentration of their own cell-free DNA. This effectively dilutes the proportion of fetal cfDNA present in the sample, leading to a lower fetal fraction percentage.
The specifics of the pregnancy can have an effect as well. Pregnancies with multiples, such as twins, or those conceived through in vitro fertilization (IVF) can sometimes be associated with lower fetal fraction levels. The use of certain medications, like low-molecular-weight heparin, may also impact the results.
Understanding a Low Fetal Fraction Result
Receiving a report with a “low fetal fraction” often leads to an inconclusive or “no-call” test result. This means the laboratory was unable to obtain enough information from the sample to provide a screening assessment. A low fetal fraction is a test limitation, not a direct indicator of a health problem with the fetus.
For many who receive this result, the cause is related to factors like a high BMI or having the blood drawn too early in the pregnancy. The most common reason for a test failure is an insufficient amount of fetal DNA in the sample. In these situations, the issue is with the sample quality, not the pregnancy itself.
While a low fetal fraction result is not a diagnosis, some studies have shown a statistical association between very low fetal fraction and an increased chance for certain chromosomal or placental conditions. This is one reason why a “no-call” result should be discussed with a healthcare provider. However, in the majority of cases, a repeat test at a later date resolves the issue.
Options After a Low Fetal Fraction Result
When an NIPT fails due to low fetal fraction, the most common first step is to repeat the blood draw. This is typically done one to two weeks later, allowing more time for the fetal fraction to increase naturally as the pregnancy progresses. Approximately half of those who have a second blood draw will receive a conclusive result.
A healthcare provider may also recommend a detailed ultrasound examination. This can be used to check on the baby’s growth, anatomy, and the health of the placenta. The ultrasound provides a different type of information than the NIPT and can be a useful next step in monitoring the pregnancy.
If a conclusive result cannot be obtained from NIPT, or if there are other concerns, alternative testing may be discussed. This could involve other screening tests or diagnostic tests, which provide a definitive “yes” or “no” answer regarding specific chromosomal conditions. Diagnostic tests include procedures like chorionic villus sampling (CVS) or amniocentesis.