Non-Invasive Prenatal Testing (NIPT) is a common screening tool, offering a way to assess the risk of certain fetal genetic conditions early in pregnancy. Receiving the results can be stressful, especially when the report contains technical language. The phrase “clinical correlation is suggested” often causes confusion for expectant parents. This article clarifies the meaning of this specific phrase and outlines the necessary next steps.
Understanding Non-Invasive Prenatal Testing
NIPT analyzes cell-free DNA (cfDNA) circulating in the pregnant person’s bloodstream. These small DNA fragments originate from both the pregnant person and the placenta, which shares the baby’s genetic material. By measuring the relative amounts of DNA from specific chromosomes, the test estimates the risk for conditions like Trisomy 21 (Down syndrome), Trisomy 18, and Trisomy 13.
NIPT is a screening test, not a diagnostic test. A screening test provides a risk score or probability, indicating an increased or decreased chance of a condition being present. It does not definitively confirm the presence or absence of a genetic disorder.
NIPT results are highly accurate but not perfect. Diagnostic tests, such as amniocentesis, are required to provide a definitive answer regarding the fetus’s genetic makeup. The test is generally performed as early as nine to ten weeks of gestation, offering earlier risk assessment than traditional methods.
Decoding “Clinical Correlation Is Suggested”
The phrase “clinical correlation is suggested” is a directive from the laboratory to the ordering healthcare provider. It means the lab detected an atypical pattern or a result that warrants further investigation, but the finding is not definitive alone. The phrase instructs the provider to integrate the lab result with all other available clinical information about the pregnancy.
This clinical information includes the pregnant person’s age, ultrasound findings, and the patient’s medical and family history. The goal of this comprehensive assessment is to determine the actual relevance of the atypical finding to the pregnancy.
The phrase often appears when a result falls into an ambiguous range or when the Positive Predictive Value (PPV) for a specific finding is lower. PPV is the probability that a positive test result correctly identifies a condition in the fetus. Even with NIPT’s high accuracy, if the condition being screened for is rare, a positive result has a higher chance of being a false positive.
The instruction for correlation is a medical safeguard. It ensures that no decisions about the pregnancy are made solely based on a screening test result. The lab is flagging an observation that requires context from the treating physician to determine the actual risk to the fetus.
Next Steps: Genetic Counseling and Confirmatory Testing
The mandatory next step following a result suggesting clinical correlation is a consultation with a certified genetic counselor. The counselor interprets the specific details of the NIPT report and explains the implications of the finding based on the patient’s individual risk factors. They provide a deeper understanding of the test’s limitations and potential outcomes, helping the patient navigate complex medical information.
The counselor will discuss proceeding with a diagnostic, confirmatory test, since NIPT alone cannot diagnose a condition. These invasive tests analyze the cells of the fetus directly, providing a definitive answer. The two primary methods are Chorionic Villus Sampling (CVS) and Amniocentesis.
Chorionic Villus Sampling (CVS)
CVS is typically performed between 10 and 13 weeks of gestation and involves sampling a small amount of tissue from the placenta.
Amniocentesis
Amniocentesis is usually performed after 15 or 16 weeks of gestation and involves collecting a small amount of the amniotic fluid surrounding the fetus.
Both procedures carry a small, procedure-related risk of miscarriage, generally estimated to be about 0.2% to 0.3% in experienced centers. The choice of diagnostic test depends on the gestational age and the specific genetic finding flagged by the NIPT. These procedures allow for a direct analysis of the fetal chromosomes, confirming or ruling out the condition indicated by the screening result.
Factors Influencing Atypical NIPT Results
The need for clinical correlation often arises because the cfDNA analyzed by NIPT originates from the placenta, which is genetically similar but not identical to the fetus.
Placental Mosaicism
One common cause of an atypical NIPT result is placental mosaicism. This occurs when a chromosomal abnormality is present only in the placenta but not in the fetus itself. In these cases, the fetus may be genetically normal despite the NIPT suggesting a high risk for a condition.
Maternal Factors
Atypical results can also stem from maternal factors that affect the cfDNA profile. The pregnant person may have an undiagnosed chromosomal difference or copy number variant contributing to the cfDNA in the blood sample. In rare instances, maternal conditions like certain cancers can release atypical cfDNA, leading to a false positive result.
Low Fetal Fraction
Another technical issue leading to correlation is a low fetal fraction. This means there was an insufficient amount of fetal DNA in the maternal blood sample for a reliable result. This can be influenced by factors such as high maternal body mass index or drawing the blood sample too early in the pregnancy. A low fetal fraction requires clinical follow-up as it can be associated with an increased risk of certain aneuploidies.