The Reliability You Want and the Accuracy You Need:
How Can Fetal Fraction Impact the Reliability of Your Non-Invasive Prenatal Test?
Liza Kunz, MD
11 June 2019
In my clinical experience as a maternal-fetal medicine physician, I have seen various non-invasive prenatal tests (NIPT) in practice. As you try to choose a test you trust for your patients, it may be hard to compare one test against another.
Fetal fraction is one important quality metric that I always consider, but it isn’t a universal standard across all NIPTs. The term fetal fraction is used often, but rarely explained, so its critical importance may not be fully realized.
So what exactly is fetal fraction and how does it impact an NIPT’s reliability?
During pregnancy, fragments of circulating cell-free DNA (cfDNA) can be found in maternal blood. These cfDNA fragments come from the mother, placenta, and the fetus. NIPTs analyze the fetal cfDNA in maternal blood to look for possible chromosomal conditions affecting the pregnancy. Therefore, if a meaningful conclusion is desired, it is imperative for the test to differentiate cfDNA from the mother from that originating from the fetus and placenta. Fetal fraction is the relative amount of fetal cfDNA in the mother’s blood compared to the total cfDNA.1,2,3
Determining the proportion of the total cfDNA that is coming from the pregnancy, or the fetal fraction, is critical for evaluating whether the pregnancy has the expected number of chromosomes.
Samples with low fetal fraction may produce results based on maternal DNA alone, and this can lead to a false negative result.1
A minimum fetal fraction requirement is necessary to ensure that the test is performing at a highly reliable standard.
This is why professional societies such as the International Society of Prenatal Diagnosis (ISPD), American College of Obstetricians and Gynecologists (ACOG) and American College of Medical Genetics and Genomics (ACMG) have emphasized the importance of including fetal fraction measurements in determining chromosomal conditions.2-4
Before ordering any NIPT, it is important to see whether the assay takes fetal fraction into consideration as a quality metric. Just having a number on a report is not enough. It is also critical to note if the test has published clinical studies in peer-reviewed journals to demonstrate the reliability and reproducibility of their fetal fraction assessment.
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