Genetic testing for Down syndrome provides insights into a pregnancy’s genetic profile. Questions about test accuracy are common. This article explores the types of tests and factors influencing their results.
Types of Genetic Testing for Down Syndrome
Genetic tests for Down syndrome fall into two main categories: screening tests and diagnostic tests. Screening tests estimate the probability of a fetus having Down syndrome, while diagnostic tests provide a definitive presence or absence of the condition.
Non-Invasive Prenatal Testing (NIPT) is a widely used screening method that analyzes small fragments of cell-free DNA from the placenta circulating in the mother’s blood. This test, typically performed after 10 weeks of gestation, measures the relative amount of chromosome 21 DNA to assess risk.
Other screening options include maternal serum screening, which measures specific hormone and protein levels in the mother’s blood, often combined with ultrasound measurements like nuchal translucency. These screenings provide a risk score but do not confirm a diagnosis.
In contrast, diagnostic tests involve obtaining fetal cells directly for chromosomal analysis. Chorionic villus sampling (CVS) collects placental tissue, usually between 10 and 13 weeks of gestation, while amniocentesis extracts amniotic fluid, typically after 15 weeks.
These diagnostic procedures analyze the fetal karyotype, identifying the extra chromosome 21. Both CVS and amniocentesis carry a small risk of complications, such as miscarriage. The choice between screening and diagnostic tests depends on individual risk factors, gestational age, and personal preferences.
Interpreting Test Results
Understanding genetic test results is essential. For screening tests like NIPT, a “positive” result indicates an elevated probability of Down syndrome, not a diagnosis. A “negative” result suggests a low probability. These probabilities are based on sensitivity and specificity.
Sensitivity refers to the test’s ability to correctly identify individuals who truly have Down syndrome. Specificity measures the test’s ability to correctly identify individuals who do not have the condition, resulting in fewer false positives.
A false positive occurs when a screening test indicates a high risk for Down syndrome, but subsequent diagnostic testing reveals the fetus does not have the condition. Conversely, a false negative happens when a screening test suggests a low risk, but the fetus is later found to have Down syndrome.
Diagnostic tests, such as amniocentesis or CVS, provide a definitive answer regarding the extra chromosome 21. While highly accurate, these tests can have rare interpretative challenges or technical limitations. A positive screening result always warrants further diagnostic investigation.
Factors Affecting Accuracy
Biological and technical factors can influence genetic test accuracy. For NIPT, maternal mosaicism, where the mother has some cells with an extra chromosome 21, can lead to a false positive. This occurs because NIPT detects the mother’s mosaicism rather than the fetal condition.
Another maternal factor is vanishing twin syndrome, where one twin with Down syndrome is reabsorbed early in pregnancy, but its DNA persists in the mother’s bloodstream, causing a false positive NIPT for the surviving fetus. Maternal conditions such as obesity or certain medications can also affect NIPT accuracy by influencing the fetal fraction. If the fetal fraction is too low, typically below 4%, the test may not yield a reliable result or could produce a false negative.
Fetal factors include confined placental mosaicism, where the extra chromosome 21 is only in the placenta, leading to a false positive NIPT. True fetal mosaicism, where only some fetal cells have the extra chromosome, can complicate diagnostic interpretation if sampled cells do not reflect all cell lines. Technical limitations and laboratory errors, such as sample mix-ups, can also contribute to inaccuracies. Performing NIPT too early might result in an insufficient fetal fraction, requiring a repeat test.
Navigating Discrepant or Uncertain Results
Receiving an unexpected or uncertain genetic test result can be concerning. When a screening test, such as NIPT, indicates high risk, seeking genetic counseling is important. A genetic counselor can interpret results, explain implications, and discuss influencing factors. They provide information and guide individuals through further investigation options.
Following an abnormal screening result, confirmatory diagnostic testing is recommended. This typically involves amniocentesis or CVS, which directly analyze fetal cells for chromosomal abnormalities. These invasive procedures offer high accuracy and can confirm or rule out Down syndrome. Decisions should not be based solely on a screening test result, as these identify risk, not provide a diagnosis.
In cases of unclear diagnostic results, such as mosaicism, further specialized genetic analysis may be pursued. This could involve analyzing different tissue samples or more detailed chromosomal studies. A multi-faceted approach involving expert consultation and confirmatory testing provides the most accurate understanding of fetal genetic status.