Fetal fraction refers to the percentage of cell-free DNA (cfDNA) in a pregnant person’s bloodstream that originates from the placenta. This small but significant proportion of DNA is a key measurement in non-invasive prenatal screening (NIPS), also known as non-invasive prenatal testing (NIPT). Understanding the fetal fraction is important because it directly impacts the reliability of these screening tests, which analyze genetic material to assess the risk of certain chromosomal conditions in the fetus.
The Origin of Fetal Fraction
During pregnancy, cells from the placenta undergo a natural process of cell death and release tiny fragments of their DNA into the pregnant person’s blood circulation. These fragments are known as cell-free DNA (cfDNA) because they are not contained within cells but rather float freely in the bloodstream. The fetal fraction represents the proportion of this total cfDNA that comes from the placenta, which shares the same genetic makeup as the developing fetus.
The placental cells, primarily cytotrophoblasts, are the source of this circulating fetal DNA. These DNA fragments are relatively small, around 200 base pairs in length, which helps distinguish them from larger maternal DNA fragments. While the exact amount can vary, fetal DNA is generally present in maternal blood after about five to seven weeks of gestation, and its concentration tends to increase as the pregnancy progresses.
The Role of Fetal Fraction in Prenatal Screening
Non-Invasive Prenatal Testing (NIPT) analyzes the cell-free DNA in a pregnant person’s blood to screen for common chromosomal conditions, such as Down syndrome (Trisomy 21), Edwards syndrome (Trisomy 18), and Patau syndrome (Trisomy 13). For NIPT to provide accurate results, there must be a sufficient amount of fetal DNA present in the blood sample.
A higher fetal fraction generally leads to more accurate NIPT results, allowing for a better distinction between normal and abnormal chromosome patterns. If the fetal fraction is too low, the test may not reliably detect chromosomal abnormalities, potentially leading to an inconclusive result or, in some cases, a false negative. Most laboratories typically require a minimum fetal fraction, often around 2% to 4%, to generate reliable NIPT results.
What Influences Fetal Fraction Levels
Several factors can affect the amount of fetal fraction circulating in a pregnant person’s blood. Gestational age is a significant factor, with fetal fraction generally increasing as the pregnancy advances. For instance, around week 10 of pregnancy, the average fetal fraction might be 4% to 6%, increasing to over 10% by week 20. This increase is likely due to the growth of the placenta and the corresponding release of more fetal DNA fragments.
Maternal weight also shows an inverse relationship with fetal fraction; higher maternal body mass index (BMI) is typically associated with a lower fetal fraction. This could be because a higher maternal weight leads to a dilution effect, where the fetal DNA is a smaller proportion of the total circulating cell-free DNA. Additionally, multiple pregnancies, such as twins, can result in a higher overall amount of cell-free DNA, but the individual fetal fractions for each fetus might vary. Certain medical conditions or medications, like those for high blood pressure or blood thinners, may also influence fetal fraction levels.
Understanding Fetal Fraction Results
When NIPT is performed, the fetal fraction is measured to ensure the test can provide a reliable outcome. A low fetal fraction means there might not be enough fetal DNA in the sample for the test to accurately distinguish between normal and abnormal chromosomal patterns. This can lead to an inconclusive NIPT result, meaning the laboratory cannot provide a definitive answer. In such cases, a repeat blood draw is often recommended, usually after a few weeks, to allow the fetal fraction to increase.
While a low fetal fraction can be a source of concern, it does not necessarily mean there is an issue with the fetus. However, some studies have indicated that a low fetal fraction may be associated with a higher risk of aneuploidy, ranging from 2.7% to 23.3%. If a repeat NIPT also yields an inconclusive result, or if there is a heightened concern, healthcare providers might suggest alternative screening options or more invasive diagnostic tests, such as amniocentesis or chorionic villus sampling (CVS), which offer more definitive answers.