Prenatal screening assesses the genetic health of a pregnancy by analyzing a simple maternal blood sample. This process examines genetic material circulating freely in the mother’s bloodstream, which includes DNA from the developing pregnancy. For the screening to be reliable, a sufficient amount of the pregnancy’s genetic material must be present. The fetal fraction quantifies this amount, defined as the percentage of the total genetic material in the sample that originated from the pregnancy. This measurement is a fundamental quality control check, ensuring the test has enough data to accurately screen for chromosomal differences.
Understanding Cell-Free DNA
Prenatal screening relies on analyzing cell-free DNA (cfDNA), which consists of small fragments of genetic material released into the blood plasma. This cfDNA circulates freely, having been released during the natural process of cell turnover. In a pregnant individual, cfDNA originates from two distinct sources: the mother’s own cells and the placenta.
The placenta sheds its genetic material directly into the maternal circulation. Since the placenta shares the same genetic makeup as the fetus, this placental DNA serves as a reliable proxy for fetal DNA. The analysis of this mixture of maternal and placental cfDNA assesses the pregnancy’s genetic profile. The proportion of this placental-derived cfDNA determines the fetal fraction measurement.
Calculating the Critical Threshold
The fetal fraction is calculated as the percentage of total cfDNA in the maternal blood sample derived from the placenta. This ratio directly measures the concentration of the pregnancy’s genetic material relative to the mother’s own cfDNA. The measurement is necessary because screening technology relies on detecting subtle proportional changes in chromosome amounts.
To ensure sufficient statistical power to accurately detect a chromosomal abnormality, a minimum amount of placental cfDNA is required. The minimum threshold for a reliable screening result is typically set at 4% of the total cfDNA in the sample. Below this benchmark, the test’s ability to distinguish between normal and abnormal chromosome counts is significantly reduced. While 4% remains the common standard, some advanced laboratory methods may report results with a fetal fraction as low as 2% to 2.5%.
Biological and Technical Factors Influencing the Fraction
The fetal fraction is dynamic and influenced by several biological and technical variables. A significant biological factor is the gestational age, as the fraction naturally increases as the pregnancy progresses. The amount of placental cfDNA is typically low before ten weeks of gestation, but it rises steadily, averaging between 10% and 15% between ten and twenty weeks.
Another influence is the mother’s body mass index (BMI). Individuals with a higher BMI often have a larger volume of circulating maternal cfDNA, diluting the concentration of placental cfDNA. This dilution results in a lower fetal fraction percentage in the sample. Multiple gestations, such as twins, generally result in a higher combined fetal fraction because two placentas contribute genetic material.
The fraction can also be affected by rare placental conditions or chromosomal abnormalities. For example, pregnancies involving trisomy 13 or trisomy 18 are sometimes associated with a lower fetal fraction. Conversely, an unusually high fraction may be observed in cases involving abnormal placental function. Technical handling also plays a role, as improper collection or processing can artificially elevate maternal cfDNA and dilute the measured fetal fraction.
When the Fetal Fraction Is Too Low
When the calculated fetal fraction falls below the laboratory’s minimum required threshold, the test is unable to provide a reliable result. This outcome is typically reported as an “inconclusive” or “no call” result, indicating insufficient placental DNA to perform the necessary analysis. A low fetal fraction prevents the test from being completed, offering neither a positive nor negative screening result.
The standard follow-up for a no-call result is a repeat blood draw, usually a few weeks later. This allows the fetal fraction time to increase naturally as the pregnancy progresses. If the fraction remains persistently low after a second attempt, alternative diagnostic testing may be recommended. These options include invasive procedures like amniocentesis or chorionic villus sampling, which provide definitive genetic information but carry a small procedural risk.
A low fetal fraction correlates with a higher underlying risk for certain fetal aneuploidies, such as trisomy 13 and 18. It also correlates with an increased risk for adverse pregnancy outcomes. These outcomes include hypertensive disorders of pregnancy, preterm birth, and impaired fetal growth. Therefore, a persistently low fraction prompts a more thorough evaluation of the pregnancy.