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For a NIPT test to provide a reliable result, a sufficiently high proportion of FF is required. Most analysis methods specify a minimum level of FF of around 2-4%, depending on the method or assay used. If the proportion is too low, the NIPT analysis may give an invalid result, which may lead to the need for a new sample.
Studies have shown that a higher FF generally improves the accuracy of the test, while a low FF can increase the risk of false negative or false positive results. Therefore, laboratories often consider FF when interpreting results, and some platforms choose not to provide a response if the FF is too low.
Factors that affect fetal fraction
FF varies between pregnancies and is affected by several factors. It is important to understand these factors because they can have a direct impact on the reliability of the test results. A low FF can lead to the test having to be repeated or giving uncertain results, while a Higher FF generally improves the accuracy of the test. Below are listed some of the most common factors that affect FF.
- Week of pregnancy: The proportion of FF generally increases with the length of pregnancy and becomes more stable after week 10.
- Maternal BMI: Overweight and obesity are associated with a lower FF, as a greater proportion of maternal DNA can be diluted in the blood.
- Multiple pregnancy: In twin pregnancies, FF can be affected and the interpretation of the results becomes more complex.
- Placental abnormalities: Conditions that affect the placenta can lead to altered FF and thus affect the test result.
- Blood sampling method: Correct sampling and handling of the blood sample can affect DNA levels and thus FF.
What happens if the fetal fraction is low?
If the FF is too low, the laboratory can either recommend a repeat sample or issue a results with lower certainty. Many analysis platforms have a limit for what they consider to be a reliable result and refrain from analyzing samples where the FF is below this limit. In cases where re-sampling is recommended, it is usually appropriate to wait a couple of weeks to give the fetal DNA levels a chance to increase. Alternatively, other diagnostic methods such as ultrasound or invasive tests (CVS or amniocentesis) can be considered if there is a high suspicion of genetic abnormalities.
How common is low fetal fraction?
- Around 3–5% of all pregnant women undergoing
- Low FF is particularly common in women with high BMI, as their circulating blood volume can dilute the fetal DNA.
- Multiple pregnancies may produce more complex FF results, where some fetuses may have different contributions to the total FF.
What is a normal fetal fraction and what levels are required for NIPT?
- Typical values: In an average pregnancy, FF is typically between 4-15%, depending on gestational age, maternal physiology, and other factors.
- Minimum level for analysis: Most laboratories require an FF of at least 2-4% to perform a reliable analysis. If the FF is below this limit, the test may need to be repeated.
- Average FF per week of pregnancy:
- Week 10: Approximately 4–6%
- Week 12: Approximately 6–10%
- Week 20: Over 10% in most cases
How does FF change when re-sampling?
- If a woman has a low FF at the first sampling, it is often recommended to wait 1–2 weeks before re-sampling, since the proportion of fetal DNA usually increases as the pregnancy progresses.
- If the FF is still low at the second sampling, alternative testing methods may be considered, such as invasive sampling (CVS or amniocentesis), especially if there is a strong suspicion of chromosomal abnormalities.