The advent of non-invasive prenatal testing (NIPT) has revolutionized prenatal care, offering pregnant individuals a highly accurate method for screening for common fetal chromosomal abnormalities. This helps parents determine prevention measures or treatments for specific genetic disorders, such as trisomy 21 (Down Syndrome).
Non-invasive prenatal testing is a screening method that analyzes cell-free DNA (cfDNA) circulating in a pregnant person’s blood. The cfDNA is a mixture of maternal and fetal DNA, the latter originating from the placenta. By sequencing the DNA, NIPT can detect an aneuploidy in the fetus. The primary indication for NIPT is to screen for the most common trisomies: Trisomy 21 (Down syndrome), Trisomy 18 (Edwards syndrome), and Trisomy 13 (Patau syndrome). It can also screen for sex chromosome aneuploidies. The test is performed via a simple blood draw from the pregnant person and can be done as early as 10 weeks of gestation.
NIPT has demonstrated outstanding performance as a screening tool, particularly for Trisomy 21. Sensitivity refers to the test’s ability to correctly identify those with the condition, while specificity refers to its ability to correctly identify those without the condition. A large-scale meta-analysis of NIPT performance found that for Trisomy 21, the pooled sensitivity was 99.7%, and the specificity was 99.6% (Gil et al., 2017). These figures indicate that NIPT is exceptionally accurate in detecting and ruling out Down syndrome, far surpassing the accuracy of older screening methods, such as maternal serum screening.
Despite its high accuracy, NIPT still has limitations that must be understood. The most important limitation is that it is a screening test, not a diagnostic test. This means it provides a risk assessment, not a definitive diagnosis. A positive NIPT result must be confirmed with a diagnostic test, such as amniocentesis or chorionic villus sampling (CVS), which analyzes fetal cells directly but carries a small risk of miscarriage.
Another limitation is related to the test’s Positive Predictive Value (PPV). The PPV is the probability that a positive screening result is a true positive. This value is highly dependent on the mother’s age and the prevalence of the condition in the population. For a young, low-risk individual, the PPV for Trisomy 21 can be lower, meaning a positive result has a higher chance of being a false positive compared to the same result in a high-risk individual (ACOG, 2020). Other limitations include the possibility of a test failure due to insufficient fetal DNA in the sample and the fact that NIPT does not screen for all genetic conditions, such as single-gene disorders, microdeletions, or structural abnormalities like neural tube defects.
Given these factors, counseling for patients considering NIPT is essential. The following recommendations should be provided:
- Patients should understand that NIPT is a highly accurate screening tool, but it is not a definitive diagnosis. Life-altering decisions should never be made based solely on an NIPT result.
- Pre-test counseling is important for setting realistic expectations. Patients should be informed about what the test screens for, its limitations, and the meaning of a positive, negative, or inconclusive result.
- Following a positive result, patients should be offered comprehensive genetic counseling and confirmatory diagnostic testing to receive a definitive diagnosis.
- Patients should be counseled on the concept of Positive Predictive Value and understand that their personal risk profile affects the interpretation of a positive result.
References
American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins—Obstetrics; Committee on Genetics; Society for Maternal-Fetal Medicine. (2020). Screening for fetal chromosomal abnormalities: ACOG Practice Bulletin, Number 226. Obstetrics and Gynecology, 136(4), e48–e69. https://doi.org/10.1097/AOG.0000000000004084
Gil, M. M., Accurti, V., Santacruz, B., Plana, M. N., & Nicolaides, K. H. (2017). Analysis of cell-free DNA in maternal blood in screening for aneuploidies: updated meta-analysis. Ultrasound in Obstetrics & Gynecology, 50(3), 302–314. https://doi.org/10.1002/uog.17484
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