Management recommendations for pregnancies complicated by low fetal fractions on cell free DNA analysis
Contributor: Dr Kacey Eichelberger
Last Update: 6/28/17
Cell-free DNA analysis and how to interpret results is an ever changing topic. The technology employed by each laboratory may be similar; however the algorithms and subsequent interpretation are extremely individualized and proprietary. This leaves us, as OB providers, without a clear set of guidelines for understanding and counseling our patients regarding the effect of situations such as a normal result in the presence of low fetal fraction.
It is clear from both published literature and clinical experience that an adequate fetal fraction is necessary for accurate results. What is not clear at this point is what range of fetal fraction is encompassed by a negative result, PPV and NPV on our patients’ reports. This leaves us with questions such as: Can a negative report be accurate when the fetal fraction is less than 1%? And if not, what is the minimal fetal fraction needed for an accurate result?
Historically, 4% was chosen as the lowest level of reported fetal fraction for accurate results. However, the technology has continued to improve significantly, and now most laboratories feel comfortable with calling a negative result with a fetal fraction of 3%. After reviewing the literature, speaking to the genetic counselors at the laboratories, and our own experience, we recommend providers consider the following guidelines when interpreting low risk (or ‘negative’) cell free DNA results with low fetal fractions:
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