From the Guidelines
A fetal fraction of 25% for non-invasive prenatal testing (NIPT) is considered high and indicates an excellent sample for testing. Typically, a fetal fraction of at least 4% is required for reliable NIPT results, with most tests requiring between 2-4% as the minimum threshold 1. At 25%, the amount of fetal DNA in the maternal blood sample is well above this minimum requirement, which means the test should provide highly accurate results with a reduced chance of test failure or inconclusive findings. This high fetal fraction occurs because there is a substantial amount of placental DNA (which represents the fetal genetic material) circulating in the maternal bloodstream.
- Factors that can influence fetal fraction include:
- Gestational age
- Maternal weight
- Certain pregnancy complications With a 25% fetal fraction, patients can feel confident in the reliability of their NIPT results, whether those results are positive or negative for the chromosomal conditions being screened. No additional testing would be needed based solely on the fetal fraction percentage, though follow-up diagnostic testing might still be recommended if the NIPT results indicate an increased risk for a chromosomal abnormality, as low fetal fractions and failed results have been associated with fetal aneuploidy 1.
From the Research
Fetal Fraction and Non-Invasive Prenatal Testing (NIPT)
- Fetal fraction (FF) is a crucial component of NIPT results, representing the proportion of fetal DNA in the maternal bloodstream 2.
- A low fetal fraction of 25% may indicate a higher risk of false negative results or failed NIPT tests 3.
- The fetal fraction can be influenced by various biological factors and bioinformatics algorithms used to interpret DNA sequencing results 2.
Implications of Low Fetal Fraction
- A low fetal fraction may require additional testing or confirmation using invasive techniques, such as amniocentesis or chorionic villus sampling 4, 5.
- Emerging solutions, such as size selection of shorter cell-free DNA fragments, may help decrease the false negative rate of NIPT and improve test accuracy 3.
- Clinicians should be aware of the potential limitations of NIPT and the importance of fetal fraction in interpreting test results 2, 6.
NIPT and Fetal Fraction Measurement
- Different sequencing technologies and bioinformatics algorithms may affect the measurement of fetal fraction, and there is no universal threshold applicable across all platforms 2.
- The development of new technologies and methods, such as targeted sequencing and assessment of single nucleotide polymorphism differences, may improve the accuracy and reliability of NIPT results 4, 6.
- Fetal fraction enrichment and improved sequencing techniques may enable the detection of additional chromosomal abnormalities and increase the sensitivity of NIPT 6, 3.