Non-Invasive Prenatal Testing (NIPT) is a common screening method during pregnancy, offering valuable insights into fetal health. This advanced blood test analyzes genetic material from the developing baby circulating in the mother’s bloodstream. A central component of NIPT is the fetal fraction, which is the proportion of cell-free fetal DNA (cffDNA) in the sample. Understanding fetal fraction is important for reliable NIPT results.
Understanding Fetal Fraction
Cell-free fetal DNA (cffDNA) fragments from the placenta enter the mother’s bloodstream, circulating alongside her own DNA. Fetal fraction quantifies the percentage of this fetal DNA relative to the total cell-free DNA (maternal and fetal) in the blood sample. The fetal DNA primarily originates from placental trophoblasts. These cffDNA fragments are typically smaller than maternal DNA fragments, which helps distinguish them during laboratory analysis. The amount of cffDNA in maternal blood becomes detectable after five to seven weeks of gestation and generally increases as the pregnancy progresses.
Significance in Prenatal Screening
Fetal fraction is important for NIPT accuracy and reliability. Sufficient fetal DNA is necessary to detect chromosomal abnormalities like Down syndrome (Trisomy 21), Edwards syndrome (Trisomy 18), and Patau syndrome (Trisomy 13). Without adequate fetal DNA, the test may not yield a reliable result. Measuring fetal fraction is part of NIPT quality control, ensuring enough cffDNA is present for confident results. A higher fetal fraction generally leads to greater confidence in the test’s accuracy, helping differentiate between normal and abnormal pregnancies.
Defining Optimal Fetal Fraction
A reliable NIPT result generally requires a fetal fraction of 4% or more, though the minimum can vary between 2% and 4% by assay. This range indicates sufficient fetal DNA for accurate analysis. A higher fetal fraction, typically 10% to 15% between 10 and 20 weeks of gestation, allows for better separation between normal and abnormal results. There is no universally agreed-upon maximum fetal fraction for valid NIPT results.
Implications of Low Fetal Fraction
A fetal fraction below the optimal threshold can lead to an “inconclusive” or “no-call” NIPT result, meaning insufficient fetal DNA for a definitive outcome. This occurs in 2% to 5% of cases. A low fetal fraction does not indicate a pregnancy problem, but rather a testing limitation. Next steps often include a redraw and retest after a few weeks to allow fetal DNA levels to increase. If a second NIPT is also inconclusive, diagnostic tests like chorionic villus sampling (CVS) or amniocentesis may be recommended.
Factors Affecting Fetal Fraction Levels
Several factors influence fetal fraction levels. Gestational age is a primary factor; fetal fraction increases as pregnancy advances, typically rising after 10 weeks. Early in pregnancy (before 9 or 10 weeks), fetal DNA levels are naturally lower. Maternal weight (BMI) also impacts fetal fraction; higher maternal weight can lead to a lower fetal fraction, possibly due to a dilutional effect where increased maternal blood volume or maternal DNA from adipose tissue dilutes the fetal DNA. Multiple pregnancies, maternal conditions, and technical aspects of blood collection can also influence fetal fraction.