Non-invasive prenatal testing (NIPT) is a blood screening method used during pregnancy. It analyzes small, cell-free DNA (cfDNA) fragments from the placenta that circulate in the mother’s blood to screen for specific fetal chromosomal conditions. A component of this test is the fetal fraction, which is the percentage of the baby’s DNA compared to the mother’s DNA in the blood sample. This measurement is a factor in the reliability of the test’s findings.
How Fetal Sex Is Determined with NIPT
Determining fetal sex with NIPT involves analyzing cfDNA for specific sex chromosomes. The test searches for genetic material from the Y chromosome. Since the mother’s DNA only contains X chromosomes, any Y chromosome fragments detected in the blood sample are understood to originate from the fetus.
This process leads to an interpretation based on detecting the Y chromosome. If the analysis identifies Y chromosome DNA, the fetus is presumed to be male. Conversely, if the analysis does not detect any Y chromosome DNA, the fetus is presumed to be female. This result for a female fetus is based on the absence of a signal, a detail with implications for the test’s accuracy.
Why Fetal Fraction Matters for a Girl Result
For a dependable NIPT result, the amount of fetal DNA in the mother’s blood must meet a minimum level. Most laboratories require a fetal fraction of around 4% to ensure the analysis is sound. If the fetal fraction is below this cutoff, there may not be enough fetal genetic material for a reliable assessment, potentially leading to an inconclusive result.
This threshold is important when the result indicates a female fetus. Because a “girl” result is determined by the absence of the Y chromosome, a low fetal fraction can create a potential issue. If the concentration of fetal DNA is insufficient, the test may fail to detect the Y chromosome even if the fetus is male, leading to an incorrect prediction of a female fetus.
When the fetal fraction is low, the small amount of Y chromosome material from a male fetus might not be detected by the test’s sequencing methods. This can lead to a “no result” or inconclusive finding for fetal sex. The Y chromosome is also smaller than other chromosomes, making its detection more sensitive to variations in sample quality and fetal fraction.
Factors That Affect Fetal Fraction Levels
One of the primary factors influencing fetal DNA is gestational age. As a pregnancy progresses, the amount of cfDNA released from the placenta into the mother’s bloodstream increases. Tests performed too early in gestation, before 10 weeks, are more likely to have a low fetal fraction.
Maternal body mass index (BMI) also plays a role. Individuals with a higher BMI have a larger blood volume, which can dilute the concentration of fetal cfDNA. This dilution results in a lower fetal fraction percentage, making it more difficult to reach the threshold for analysis.
Certain conditions related to the pregnancy can affect fetal fraction levels. For instance, the presence of a “vanishing twin,” where one of a pair of twins ceases to develop, can release DNA that complicates the interpretation of the test. Placental abnormalities can also impact the amount of cfDNA that enters the maternal circulation, sometimes leading to atypical NIPT results.
Interpreting Inconclusive or Atypical Findings
When NIPT does not yield a conclusive result, the primary reason is a fetal fraction that is too low for confident analysis. This is not a test failure but an indication that the sample lacked sufficient fetal DNA for a reliable assessment.
If a result is inconclusive due to low fetal fraction, the recommendation is to repeat the blood draw. This is scheduled a few weeks after the initial test to allow time for the fetal fraction to increase with advancing gestational age. Waiting for a week or two can be enough to obtain a sample that meets the required threshold. It is also important to remember that NIPT is a screening test, not a diagnostic one.