From the Guidelines
Fetal fraction testing is a crucial component of non-invasive prenatal testing (NIPT) that measures the proportion of circulating DNA in the mother's bloodstream that is of placental origin, with a threshold of at least 4% typically required for accurate results. This test is used to determine the accuracy of NIPT results in detecting chromosomal abnormalities such as Down syndrome, Edwards syndrome, and Patau syndrome 1. The fetal fraction is calculated as the proportion of circulating DNA that is from the placenta, and not maternal, with optimal management of pregnancies with low fetal fraction or "no-call" results remaining unclear 1.
Some key points to consider when interpreting fetal fraction testing results include:
- 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% to 80% of the time 1
- Certain maternal conditions, such as the use of certain anticoagulants, autoimmune disorders, and obesity, have been associated with higher "no-call" rates 1
- Technological interventions may mitigate the impact of low fetal fraction, but the optimal approach for individuals with these concurrent conditions is unclear 1
In terms of clinical implications, healthcare providers should consider offering diagnostic testing to individuals with a "no-call" result, as recommended by the American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine 1. Additionally, understanding fetal fraction is important because it directly impacts the reliability of NIPT results and helps healthcare providers determine next steps in prenatal care. Factors that can affect fetal fraction include maternal weight, gestational age, and certain pregnancy complications, highlighting the need for careful consideration of these factors when interpreting test results 1.
From the Research
Fetal Fraction Testing
- Fetal fraction testing is a quality control component of noninvasive prenatal testing (NIPT) results, which measures the percentage of fetal DNA in a maternal blood sample 2.
- The test is used to assess fetal anomalies, such as chromosomal aneuploidies, and the ability to detect these anomalies is directly related to the fetal fraction (FF) in the sample 3.
Factors Affecting Fetal Fraction
- Gestational age has been found to have a significant association with low fetal fraction (LFF), with lower gestational ages being associated with LFF 3.
- Maternal age, weight, and Body Mass Index (BMI) have not been found to have a statistically significant effect on LFF 3, 4.
- Biological factors, such as the increase in weight and BMI, can have a negative influence on fetal fraction 4.
Importance of Fetal Fraction Testing
- Fetal fraction testing is essential for noninvasive prenatal screening (NIPS) to avoid false-negative results 4.
- The test has superior test characteristics compared to traditional screening using ultrasound and serum markers, including a higher detection rate and positive predictive value, and a lower false-positive rate 5.
- However, the test is not diagnostic and does not replace invasive testing for confirmation of fetal chromosomal disorders 5.
Clinical Applications
- Fetal fraction testing is used for primary screening in high-risk women and is rapidly expanding to all women 5.
- The test can be used to detect fetal trisomies by analysis of cell-free DNA in maternal blood from as early as 10 weeks of gestation 6.
- Clinicians need to understand the biological influences on fetal fraction to provide optimal post-test counseling and clinical management 2.