The Non-Invasive Prenatal Test (NIPT) is a screening method that offers information about the likelihood of certain genetic conditions in the fetus. It transformed prenatal care by providing a non-invasive way to assess risk for chromosomal abnormalities. This article clarifies NIPT’s role in screening for Trisomy 18, also known as Edwards Syndrome.
Understanding the Non-Invasive Prenatal Test
The Non-Invasive Prenatal Test is a blood test performed on the pregnant person, starting as early as ten weeks of gestation. It is considered a screening tool, which means it estimates the risk of a condition rather than providing a definitive diagnosis. The test is non-invasive because it involves only a blood draw from the mother, posing no physical risk to the fetus.
The mechanism of NIPT relies on the presence of cell-free DNA (cfDNA) circulating in the maternal bloodstream. These minute DNA fragments originate primarily from the placenta and are genetically identical to the fetus. By analyzing the quantity of cfDNA from specific chromosomes, laboratories can detect an imbalance, such as an extra copy of a chromosome, which suggests an increased risk for an aneuploidy.
NIPT is primarily designed to screen for the three most common autosomal trisomies: Trisomy 21 (Down syndrome), Trisomy 13 (Patau syndrome), and Trisomy 18. Some NIPT panels also screen for conditions involving the sex chromosomes and certain microdeletions. The reliability of the test depends on having a sufficient amount of fetal DNA, known as the fetal fraction, which generally reaches the necessary threshold around the tenth week of pregnancy.
Trisomy 18 (Edwards Syndrome) Explained
Trisomy 18 is a genetic condition caused by the presence of a third copy of chromosome 18 in the body’s cells, rather than the usual two. This chromosomal imbalance results from a random event during the formation of the egg or sperm, and the risk increases with the mother’s age. Over 90% of cases involve the full form, where the extra chromosome 18 is present in every cell.
The presence of this extra genetic material affects development. Babies with Edwards Syndrome often have congenital heart defects, kidney abnormalities, and profound developmental delays. The condition is associated with a high rate of miscarriage or stillbirth, and for those born alive, the median lifespan is typically short, with fewer than 10% surviving past their first year.
NIPT’s Role in Screening for Trisomy 18
NIPT screens for Trisomy 18. The test assesses the likelihood of this condition by quantifying the amount of chromosome 18 cfDNA relative to other chromosomes in the maternal blood sample. A higher-than-expected count of chromosome 18 fragments suggests the fetus may have three copies of that chromosome.
The performance of NIPT for Trisomy 18 demonstrates impressive sensitivity and specificity in clinical studies. Sensitivity, the test’s ability to correctly identify affected pregnancies, is consistently reported to be above 96%, with some studies indicating a sensitivity of 97.4%. Specificity, the ability to correctly identify unaffected pregnancies, is also excellent, often reported as greater than 99.9% for Trisomy 18.
The Positive Predictive Value (PPV) is an important concept to understand, as it represents the chance that a positive screening result truly indicates the presence of the condition. Because Trisomy 18 is less common than Trisomy 21, the PPV for T18 is generally lower than that for T21, meaning a positive result for Trisomy 18 is less likely to be a true positive compared to a positive result for Trisomy 21. However, the high sensitivity and specificity mean that a low-risk NIPT result significantly reduces the probability of the condition being present.
Interpreting Results and Next Steps
NIPT results are typically reported as either “low risk” or “high risk” for the conditions screened, including Trisomy 18. A low-risk result is reassuring, as the high Negative Predictive Value (NPV) of NIPT suggests the condition is highly unlikely. However, even a low-risk result cannot guarantee the complete absence of Trisomy 18 or other genetic issues.
Conversely, a high-risk result for Trisomy 18 means there is a significantly increased probability of the condition, but it is not a diagnosis. This result must be viewed as an indication for further investigation before any medical decisions are made. The next step following a high-risk NIPT result is a referral for genetic counseling, which provides detailed information about the condition and subsequent testing options.
To confirm or rule out the suspected diagnosis, an invasive diagnostic test is necessary. These tests, which include Chorionic Villus Sampling (CVS) or Amniocentesis, analyze cells directly from the placenta or amniotic fluid, providing a definitive answer about the fetal chromosome status. While invasive tests carry a small risk of complication, they are the only way to obtain a certain diagnosis following a high-risk NIPT screening.