From the Guidelines
The minimum fetal fraction required for accurate non-invasive prenatal testing (NIPT) is generally 4%. This threshold is considered the standard cutoff by most commercial NIPT providers, below which results may be unreliable or the test might fail to produce a result 1. Fetal fraction refers to the proportion of cell-free DNA in the maternal blood that originates from the placenta, which serves as a proxy for fetal DNA. Several factors can affect fetal fraction, including:
- Maternal weight (higher BMI typically correlates with lower fetal fraction)
- Gestational age (fetal fraction increases with advancing pregnancy)
- Certain chromosomal abnormalities like trisomy 13,18, or triploidy which may be associated with lower fetal fractions 1. If a patient receives a "no call" or failed result due to low fetal fraction, options include:
- Repeating the test later in pregnancy when fetal fraction may be higher
- Considering alternative testing methods such as diagnostic procedures like amniocentesis or chorionic villus sampling 1. The 4% threshold exists because below this level, the statistical algorithms used to detect chromosomal abnormalities cannot reliably distinguish between normal and abnormal results, potentially leading to false negatives or false positives. It is also important to note that a no-call result may be associated with a higher risk of fetal chromosome disorders, and therefore, diagnostic testing should be offered to individuals with a no-call result 1.
From the Research
Fetal Fraction Testing and Meanings
- Fetal fraction (FF) is a critical component of non-invasive prenatal testing (NIPT) that measures the proportion of cell-free DNA (cfDNA) in maternal plasma that originates from the fetus 2, 3.
- The minimum fetal fraction required for accurate NIPT is not universally defined, but studies suggest that detection of common aneuploidies is possible with an FF as low as 2% 2.
- A fetal fraction of ≥ 4% is often suggested for a reportable result, but this threshold may not be applicable across all platforms, and emerging solutions are being developed to address the challenges of samples with low FF 2, 3.
Factors Influencing Fetal Fraction
- Biological factors, such as maternal weight and gestational age, can influence FF, and bioinformatics algorithms used to interpret DNA sequencing results can also impact FF measurements 3.
- The likelihood of a successful redraw is significantly dependent on the initial FF, maternal weight, and time between blood draws 4.
Clinical Implications
- Clinicians should understand the biological influences on FF to provide optimal post-test counseling and clinical management, and be aware of the variations between different sequencing technologies used by different laboratories 3.
- The use of a fetal fraction-based risk algorithm and probability of an informative redraw can help in the decision-making process for women with an initial uninformative NIPT result 4.
- Chorionic villus sampling (CVS) and amniocentesis are diagnostic procedures that can be used to confirm positive NIPT results, but the choice of procedure depends on various factors, including gestational age and ultrasound findings 5, 6.