Fetal fraction is a measurement that has become a part of modern prenatal screening. It refers to the percentage of cell-free DNA (cfDNA) from the developing baby that is found in the mother’s bloodstream during pregnancy. This measurement plays a role in non-invasive prenatal testing (NIPT), a screening method used to assess the genetic health of the fetus. Understanding fetal fraction is important for interpreting NIPT results, as it influences the accuracy of the test.
Understanding Fetal Fraction
Fetal fraction represents the proportion of the baby’s DNA circulating in the mother’s blood compared to the mother’s own cfDNA. During pregnancy, small fragments of DNA from the placenta, which is genetically similar to the fetus, are released into the mother’s bloodstream. These fragments are collected through a simple blood draw from the mother, performed after 10 weeks of gestation.
A sufficient fetal fraction is necessary for NIPT to accurately analyze the baby’s genetic material. The test relies on distinguishing between the mother’s and the baby’s DNA to screen for certain chromosomal conditions, such as Down syndrome (Trisomy 21), Edwards syndrome (Trisomy 18), and Patau syndrome (Trisomy 13). A higher fetal fraction leads to more accurate NIPT results, improving the test’s sensitivity and specificity.
What Constitutes a Normal Fetal Fraction?
What is considered a “normal” or “adequate” fetal fraction can vary slightly among laboratories and specific NIPT assays. A minimum threshold of 4% is commonly cited for reliable NIPT results. Some studies suggest that detection of common aneuploidies is possible with a fetal fraction as low as 2%. Most pregnancies have a fetal fraction ranging from 4% to 15%.
Fetal fraction naturally increases as the pregnancy progresses. For example, at 10 weeks of gestation, the average fetal fraction is around 4% to 6%, increasing to over 10% by 20 weeks. Between 10 and 20 weeks of gestation, the average fetal fraction is often reported to be between 10% and 15%. This increase is why NIPT is recommended after the tenth week of pregnancy.
Implications of Abnormal Fetal Fraction Levels
When fetal fraction levels fall outside the expected range, it can impact NIPT results. A low fetal fraction is a common reason for an inconclusive or “no result” NIPT outcome. This happens when there isn’t enough fetal DNA in the sample for the test to reliably distinguish between normal and abnormal chromosomal patterns. Low fetal fraction can also increase the risk of false negative or false positive results, though most laboratories will not report results if the fetal DNA is insufficient for accuracy.
In cases of a low fetal fraction, healthcare providers may recommend a repeat blood draw, often a few weeks later, to allow the fetal fraction to increase. If repeat testing is also inconclusive, or if there are other concerns, alternative diagnostic tests like chorionic villus sampling (CVS) or amniocentesis may be suggested. A persistently low fetal fraction can sometimes be associated with a higher risk of certain fetal chromosome disorders. While less common, an unusually high fetal fraction, particularly in the first trimester, has been linked to certain pregnancy complications, such as an abnormally invasive placenta or a higher risk of low birth weight.
Factors Influencing Fetal Fraction
Several biological and physiological factors can influence the level of fetal DNA in the mother’s blood. Gestational age is a primary factor, with fetal fraction increasing as the pregnancy advances. The fetal fraction rises, especially after 9 or 10 weeks, which is why NIPT is performed around this time.
Maternal weight also plays a role, with higher maternal weight often correlating with a lower fetal fraction. This is thought to be due to a dilutional effect, where a greater volume of maternal blood dilutes the fetal cfDNA. In multiple pregnancies, such as twins, the combined fetal fraction can be higher than in singleton pregnancies. However, the “per fetus” fetal fraction in twins can be lower than in singletons, which may lead to higher test failure rates. Other factors that can affect fetal fraction include certain maternal medical conditions, some medications, and even the method of sample collection and processing.