Non-Invasive Prenatal Testing (NIPT) offers expectant parents a screening option during pregnancy to assess the likelihood of certain chromosomal conditions in the fetus. This test analyzes genetic material from the placenta circulating in the mother’s blood, providing an early indication of potential risks. Understanding the accuracy of NIPT, particularly the concept of “false negative rates,” is important for informed decision-making. This article explores what false negative results are and the factors that can influence NIPT accuracy.
How NIPT Works
NIPT operates by analyzing fragments of cell-free DNA (cfDNA) found in a pregnant person’s bloodstream. These DNA fragments originate from both the mother and the placenta, which typically shares the same genetic makeup as the fetus. By examining the proportions of these DNA fragments, laboratories can detect an increased or decreased amount of genetic material that may indicate a chromosomal abnormality.
This screening method commonly identifies conditions such as Trisomy 21, also known as Down syndrome, which involves an extra copy of chromosome 21. It also screens for Trisomy 18 (Edwards syndrome), characterized by an extra chromosome 18, and Trisomy 13 (Patau syndrome), caused by an extra chromosome 13. Some NIPT panels also screen for sex chromosome aneuploidies (atypical X or Y chromosomes) and certain microdeletions or microduplications.
Understanding False Negative Results
A “false negative” in the context of NIPT occurs when the test indicates a low probability for a chromosomal abnormality, but the fetus actually has the condition. This means the screening test failed to detect the abnormality. The test result suggests a typical genetic profile, yet the underlying chromosomal difference exists.
A true negative result, in contrast, correctly identifies that the fetus does not have the screened-for chromosomal abnormality. This distinction highlights the challenge of false negatives, where a reassuring test result does not align with the fetus’s actual genetic status. Understanding this difference is important for interpreting NIPT results accurately.
Reasons for False Negative Results
Several biological and technical factors can contribute to a false negative NIPT result. One biological explanation is confined placental mosaicism (CPM), a condition where chromosomal abnormalities are present in the placenta’s cells but not in the fetal cells. Since NIPT analyzes placental cfDNA, CPM can lead to a normal cfDNA signal in the maternal blood, even if the fetus is affected by a chromosomal condition not reflected in the placental sample.
Another contributing biological factor can be the presence of a vanishing twin, where one twin with a chromosomal abnormality is reabsorbed early in pregnancy. Residual cfDNA from the vanished twin might still circulate, influencing the NIPT result. However, the amount of affected cfDNA might be too low to trigger a high-risk result, leading to a false negative.
Technical challenges, such as a low fetal DNA fraction, represent a common reason for inaccurate NIPT results. Fetal DNA fraction refers to the proportion of placental cfDNA relative to the total cfDNA in the mother’s blood sample. If this fraction is too low, the laboratory may not have enough fetal genetic material to accurately assess the chromosomes, potentially leading to a “no call” result or, in some instances, a false negative.
Factors influencing a low fetal DNA fraction include a high maternal body mass index (BMI), which can dilute the fetal cfDNA in the maternal bloodstream. Testing too early in gestation, typically before 10 weeks of pregnancy, also often results in an insufficient fetal fraction because the placenta has not yet released enough cfDNA into the mother’s circulation. Certain maternal medical conditions or medications can also affect the amount of circulating fetal DNA, further complicating accurate analysis.
Actual False Negative Rates and Their Significance
The reported false negative rates for NIPT are generally very low, particularly for the most common conditions. For Trisomy 21 (Down syndrome), studies have indicated false negative rates as low as 0.01% to 0.09%. This means that for every 10,000 pregnancies screened, only 1 to 9 cases of Trisomy 21 might be missed by the NIPT, resulting in a low-risk report.
For Trisomy 18 (Edwards syndrome) and Trisomy 13 (Patau syndrome), the reported false negative rates are also low, though they can be slightly higher than for Trisomy 21. These low rates signify the test’s high sensitivity in detecting these specific chromosomal abnormalities.
It is important to remember that NIPT functions as a screening test, not a diagnostic one. A low-risk NIPT result significantly reduces the probability of a chromosomal abnormality, but as a screening test, it provides a statistical likelihood, not a definitive diagnosis.
Therefore, any NIPT result, whether indicating low or high risk, should be interpreted alongside other clinical information, such as ultrasound findings or family history. A reassuring NIPT result does not negate the need for further investigation if other concerns arise during pregnancy.
Navigating NIPT Results and Next Steps
Understanding NIPT results often benefits from comprehensive genetic counseling both before and after the test. Genetic counselors can explain the capabilities and limitations of NIPT, including the concept of false negative rates, helping parents make informed decisions about testing. They can also discuss what different results might mean for a pregnancy.
If a NIPT result indicates a low risk but there are other clinical concerns, such as atypical ultrasound findings, further diagnostic testing may be recommended. Invasive diagnostic procedures like amniocentesis or chorionic villus sampling (CVS) provide a definitive diagnosis by directly analyzing fetal cells, offering a conclusive answer regarding the presence or absence of a chromosomal condition.
Similarly, if an NIPT returns a “no call” result due to insufficient fetal DNA fraction, healthcare providers might suggest a redraw of the blood sample or discuss the option of diagnostic testing. The ultimate goal is to empower expectant parents with accurate information, enabling them to make choices that align with their personal values and pregnancy management plan.