Non-Invasive Prenatal Testing (NIPT) is a common screening test performed early in pregnancy to assess the likelihood of specific chromosomal conditions in the developing fetus. The test analyzes cell-free DNA (cfDNA)—tiny fragments of genetic material from the placenta—circulating in the mother’s bloodstream, which typically mirrors the fetal genetic makeup. NIPT provides an early indication of risk for genetic variations without posing any physical risk to the pregnancy. Understanding the terminology on the resulting report is necessary for interpreting the results.
The Format of NIPT Results
NIPT results are typically presented as a binary outcome for each genetic condition screened. The report will categorize the finding as either “Low Risk,” “Negative,” or “No Aneuploidy Detected,” which indicates that the chance of the fetus having the condition is very small. Conversely, a report might show a “High Risk,” “Positive,” or “Aneuploidy Detected” result, signifying an increased probability that the condition is present. This risk is usually reported as a ratio or a percentage.
The report often separates the findings for each chromosome, meaning one condition could be “High Risk” while all others are “Low Risk.” Fetal sex is also typically reported alongside these findings, determined by the presence or absence of the Y chromosome sequences in the cfDNA. These labels are risk indicators, not definitive statements about the fetus’s health.
Interpreting Specific Screened Conditions
The focus of most NIPT panels is on the three most common autosomal trisomies, which are conditions caused by having three copies of a specific chromosome instead of the usual two. Trisomy 21 (Down Syndrome) is the most frequently screened condition, resulting from an extra copy of chromosome 21. Trisomy 18 (Edwards Syndrome) involves an extra copy of chromosome 18, and Trisomy 13 (Patau Syndrome) involves an extra copy of chromosome 13.
These three trisomies are associated with varying degrees of intellectual disability and physical malformations. T18 and T13 generally have more severe prognoses than T21. Beyond the autosomes, NIPT often screens for sex chromosome aneuploidies, which involve variations in the number of X and Y chromosomes. Examples include Monosomy X (Turner Syndrome) or Klinefelter Syndrome (XXY).
Why NIPT is a Screening Tool, Not a Diagnosis
A distinction exists between a screening test, which estimates risk, and a diagnostic test, which provides a definitive yes or no answer. NIPT is characterized by high sensitivity, meaning it is highly accurate at correctly identifying affected pregnancies, and high specificity, meaning it is excellent at correctly identifying unaffected pregnancies. The Positive Predictive Value (PPV) is the true probability that a “High Risk” result is correct.
The PPV is not a fixed number but changes based on the prevalence of the condition in the tested population, which correlates strongly with the mother’s age. For conditions with very low prevalence, like Trisomy 13 or 18 in a younger population, the PPV can be substantially lower than for Trisomy 21. A “High Risk” result does not guarantee the fetus has the condition because the cfDNA analyzed comes from the placenta, not the fetus itself. This discrepancy, known as confined placental mosaicism (CPM), occurs when the placenta has an abnormal set of chromosomes, but the fetus does not, leading to a false positive NIPT result.
Next Steps Following a High-Risk Result
Receiving a “High Risk” NIPT result necessitates an immediate consultation with a genetic counselor to discuss the specific PPV of the finding and the procedural steps for confirmation. The next step involves a diagnostic test to examine the actual fetal DNA, which is the only way to obtain a definitive diagnosis. These tests are invasive and carry a small, procedure-related risk of miscarriage, which is why they are not performed unless a high-risk screening result warrants confirmation.
The two main diagnostic procedures are Chorionic Villus Sampling (CVS) and Amniocentesis. CVS is typically performed earlier in the pregnancy, between 11 and 13 weeks, by taking a small tissue sample from the placenta. Amniocentesis is performed after 15 weeks and involves sampling the amniotic fluid surrounding the fetus. Because CVS analyzes placental tissue, it is subject to the same confined placental mosaicism issue that caused the initial NIPT concern. Amniocentesis is often the preferred confirmatory test, particularly for rarer aneuploidies like Trisomy 13 or Monosomy X.