Non-Invasive Prenatal Testing (NIPT) is a screening method that assesses the likelihood of certain fetal chromosomal conditions early in pregnancy. This technology analyzes small fragments of genetic material, known as cell-free DNA (cffDNA), circulating in the mother’s bloodstream. Receiving a result stating there is “not enough fetal DNA” can cause concern, but this outcome is often a technical limitation of the test itself. This inconclusive result, sometimes called a “no-call” or test failure, occurs when the proportion of the baby’s DNA is too low for the laboratory to provide a reliable assessment.
What is Fetal Fraction and Why Does it Matter
The concept of “fetal fraction” (FF) is central to understanding NIPT results, representing the percentage of the total cell-free DNA (cffDNA) in the maternal blood that originates from the placenta. During pregnancy, the placenta constantly sheds its genetic material into the mother’s circulation, and this material serves as a proxy for the fetus’s DNA. The total pool of cffDNA in the mother’s plasma is a mixture of the mother’s own DNA fragments and fragments from the placenta.
The fetal fraction directly impacts the accuracy and reliability of the screening test. To accurately detect subtle changes in chromosome counts, the test requires a sufficient “signal” from the fetus. Most commercial NIPT platforms establish a minimum required threshold, commonly estimated at four percent.
If the fetal fraction falls below this minimum four percent level, the algorithms used to analyze the DNA cannot reliably distinguish between a normal and an abnormal result. An insufficient fetal signal increases the risk of a false negative result, potentially missing an abnormality, leading laboratories to issue an unreportable or inconclusive result.
Factors That Reduce Fetal DNA Concentration
The most frequent reason for low fetal fraction relates to the mother’s body mass index (BMI). As maternal weight increases, the concentration of the mother’s own cell-free DNA rises, effectively diluting the fixed amount of placental DNA. A higher BMI means the body’s larger plasma volume contributes to this dilution effect. Studies demonstrate a clear inverse relationship: higher maternal BMI correlates with a lower measurable fetal fraction. This is a physiological phenomenon and does not imply a problem with the pregnancy.
Gestational age at the time of collection is another factor influencing the percentage. The amount of placental DNA shed into the mother’s blood naturally increases as the pregnancy progresses. Testing performed too early, particularly before the recommended minimum of ten weeks, often results in a low fetal fraction because the placenta has not grown large enough to release sufficient DNA.
Certain maternal health conditions can also contribute to a lower fetal fraction. The use of low molecular weight heparin (LMWH) or other blood thinners has been linked to NIPT test failures. Similarly, some autoimmune disorders may affect the overall balance of cell-free DNA in the maternal circulation.
Less commonly, placental function itself can impact the amount of DNA available for testing. If the placenta is not functioning optimally or has a low turnover rate of cells, less genetic material is released into the bloodstream. This can sometimes be the case in pregnancies where the fetus or placenta has certain underlying chromosomal abnormalities.
What A Low Fetal Fraction Result Indicates
For the majority of patients, a low fetal fraction result indicates a technical failure, meaning the sample did not meet quality control standards. This result most often reflects factors like early timing of the test or higher maternal BMI. In these instances, the result provides no information about the baby’s health status.
Clinicians cannot entirely dismiss the result, as studies demonstrate a statistical association between persistent low fetal fraction and a higher risk of certain rare fetal chromosomal disorders. Extremely low fetal fractions have been linked to conditions such as trisomy 13, trisomy 18, and triploidy. The biological mechanism is thought to involve placental dysfunction or a smaller placenta in these affected pregnancies.
This is a correlation observed in large data sets, not a diagnosis. The rate of chromosomal abnormalities in cases of “no-call” results is statistically higher than in the general population, ranging from approximately three to twenty-three percent depending on the study. This heightened risk requires further clinical attention and a thorough discussion with a genetic counselor.
Follow-Up Diagnostic Options
When a low fetal fraction result is returned, the initial management strategy involves steps to obtain a definitive answer. The most common first step is a repeat NIPT blood draw, often called a redraw. This approach is successful if the initial test was conducted early, allowing the fetal fraction to naturally increase over two to three weeks.
The success rate for obtaining a conclusive result on a repeat test is high, ranging from approximately 75 to 80 percent. If the low fetal fraction persists after a second attempt, or if the initial result was accompanied by other clinical concerns, the healthcare provider will recommend a detailed ultrasound examination. This advanced imaging checks for physical signs or “soft markers” that might suggest an underlying chromosomal condition.
The most definitive option for diagnosis remains invasive testing, such as Chorionic Villus Sampling (CVS) or Amniocentesis. These procedures collect cells directly from the placenta or amniotic fluid, providing the genetic material needed for a conclusive diagnosis, regardless of the fetal fraction. A genetic counselor will discuss the risks and benefits of these diagnostic tools to help families make an informed decision.