What Does "Fetal Fraction" Mean on Unity Genetics Screening?
Fetal fraction is the percentage of cell-free DNA in your blood that comes from the placenta (representing the fetus), as opposed to your own maternal DNA—typically 10-15% of the total circulating DNA by 10 weeks gestation. 1, 2
Why Fetal Fraction Matters
The fetal fraction is critical because NIPT analyzes this placental DNA to screen for fetal chromosome abnormalities. 1 A minimum fetal fraction of approximately 4% is required to provide reliable NIPT results, though most laboratories prefer higher thresholds for optimal accuracy. 2
- When fetal fraction is too low (below the laboratory's threshold), you receive a "no-call" result, which occurs in approximately 1% of NIPT samples 1
- The most frequent explanation for no-call results is insufficient fetal fraction 1
- Repeat testing at a later gestational age provides a result approximately 75-80% of the time 1, 2
Factors That Lower Your Fetal Fraction
Maternal Factors (Most Common)
- High maternal BMI is the strongest predictor: NIPT may fail in 20% of women with high BMI and 50% of women with very high BMI 2
- Use of certain anticoagulants can interfere with cell-free DNA analysis 2
- Maternal autoimmune conditions are linked to higher no-call rates 2
Gestational Age
- Fetal fraction is typically lower at very early gestational ages (before 10 weeks) 2
- Fetal fraction generally increases with advancing gestational age, though not always linearly 3
Fetal and Placental Factors
- Low fetal fraction has been associated with higher rates of certain chromosome disorders, particularly trisomies 13 and 18, and triploidy 2
- Multiple gestations affect fetal fraction measurements 2
- Male fetuses may have slightly lower fetal fractions than female fetuses 3
What Happens If Your Fetal Fraction Is Low
If you receive a no-call result due to low fetal fraction, the American College of Obstetricians and Gynecologists recommends offering diagnostic testing (amniocentesis or CVS). 1, 2
Your clinical pathway:
- First option: Repeat NIPT at a later gestational age (succeeds 75-80% of the time) 1, 2
- Second option: Proceed directly to diagnostic testing with amniocentesis or CVS 1
- Alternative: Consider traditional screening methods if you have high BMI or other factors predisposing to low fetal fraction 2
Important Clinical Context
Some studies have demonstrated a higher than expected rate of fetal chromosome disorders in pregnancies with no-call results, though other studies have not confirmed this association. 1 This uncertainty is why diagnostic testing is offered rather than simply repeating NIPT indefinitely.
Additionally, low fetal fraction in the first and early second trimesters has been associated with adverse pregnancy outcomes, particularly hypertensive disease of pregnancy, suggesting it may serve as a predictive marker beyond just chromosome screening. 4
Technical Variability You Should Know About
There is substantial variability in how different laboratories measure and report fetal fraction—the same sample can yield different fetal fraction values depending on the testing platform and bioinformatics method used. 5 Fetal fraction should be regarded as a laboratory-specific range rather than a precise number, and applying strict universal minimum thresholds may result in unnecessary test failures. 5