What is fetal fraction?

• Definition: Fetal fraction (FF) refers to the proportion of cell-free fetal DNA (cffDNA) circulating in maternal blood. It's expressed as a percentage of total cell-free DNA (cfDNA) in the maternal plasma.

• Origin: cffDNA originates primarily from the placenta, specifically from apoptotic trophoblast cells.

• Clinical Significance:

  • Non-invasive Prenatal Testing (NIPT): FF is crucial for the accuracy of NIPT, which screens for chromosomal abnormalities like Down syndrome (Trisomy 21), Edwards syndrome (Trisomy 18), and Patau syndrome (Trisomy 13). A sufficient fetal fraction is required for reliable results.
  • Fetal Sex Determination: Fetal fraction allows for the determination of fetal sex as early as 7 weeks gestation.
  • Rhesus D (RhD) blood type determination: Determining the fetal fraction enables the determination of fetal RhD blood type in RhD negative mothers.
  • Prediction of adverse pregnancy outcomes: Low fetal fraction has been associated with increased risk of adverse pregnancy outcomes such as preeclampsia, fetal growth restriction, preterm birth, and fetal demise.

• Factors Affecting Fetal Fraction:

  • Gestational Age: FF generally increases with advancing gestational age.
  • Maternal Weight: Higher maternal weight is associated with lower FF.
  • Multiple Gestations: Pregnancies with twins or higher-order multiples have higher FF.
  • Aneuploidy: Certain fetal aneuploidies (e.g., Trisomy 21) may affect FF.
  • Maternal Diseases: Conditions such as autoimmune diseases or certain medications can impact FF.

• Low Fetal Fraction:

  • A low fetal fraction can lead to a "no result" or an inaccurate NIPT result.
  • If FF is too low, repeat testing may be recommended.
  • In some cases, invasive diagnostic procedures (e.g., amniocentesis, chorionic villus sampling) may be considered if NIPT results are inconclusive.

• Measurement: Fetal fraction is estimated using sequencing data from NIPT. Algorithms analyze the proportion of fetal-specific DNA sequences present in the maternal plasma sample.