Nipt Test: Purpose, Test Details & Results

Purpose of Nipt Test

Non-invasive prenatal testing (NIPT) has revolutionized prenatal care, offering expectant parents a highly accurate, low-risk way to screen for certain genetic conditions in their unborn child. By analyzing small fragments of fetal DNA circulating in the mother's blood, NIPT allows for early detection of chromosomal abnormalities without the risks associated with traditional invasive testing methods. As NIPT becomes more widely adopted globally, understanding its purpose, strengths, and limitations is essential for both families and healthcare providers.

Table 1: Main Purposes and Benefits of NIPT

What Is NIPT and Why Is It Used?

NIPT is a cutting-edge screening test performed during pregnancy to assess the risk that a fetus has certain chromosomal abnormalities. The most common conditions screened are:

• Trisomy 21 (Down syndrome)
• Trisomy 18 (Edwards syndrome)
• Trisomy 13 (Patau syndrome)
• Sex chromosome aneuploidies (e.g., Turner syndrome, Klinefelter syndrome)

NIPT analyzes cell-free fetal DNA (cfDNA) found in the maternal bloodstream. Because this test is non-invasive—requiring only a maternal blood sample—it avoids the small but real risks (like miscarriage) associated with invasive diagnostic procedures such as amniocentesis or chorionic villus sampling (CVS) 1 3 5 10.

Advantages Over Traditional Screening

Traditional first-trimester screening combines blood tests and ultrasound, but these methods have lower sensitivity and higher false positive rates compared to NIPT. NIPT’s high accuracy allows for:

• Earlier, more reliable information (typically available from 10 weeks gestation)
• Significant reduction in unnecessary invasive procedures, as fewer women are referred for confirmatory testing following a negative NIPT 1 3 5.

Expanded Applications of NIPT

While NIPT was initially developed for common trisomies, technological advances now allow for the detection of sex chromosome abnormalities and even sub-chromosomal copy number variants (CNVs) and microdeletions (e.g., DiGeorge syndrome). However, the clinical validity and utility of expanded NIPT for rare conditions are still under evaluation and can vary between laboratories 4 13.

The Role of Genetic Counseling

Professional guidelines consistently recommend that NIPT be offered alongside genetic counseling. This ensures that families understand the benefits, limitations, and possible outcomes of testing, supporting informed decision-making 1 10.

Nipt Test Details

Understanding the logistics and science behind NIPT helps demystify the process for expectant parents. From how the test is performed to what it measures, the details of NIPT are critical to its success as a modern prenatal screening tool.

Table 2: Key Steps and Features of the NIPT Process

How the NIPT Test Works

NIPT utilizes advanced laboratory techniques to analyze fragments of cfDNA in a sample of the mother’s blood. These DNA fragments originate from both the mother and the placenta (which typically reflects the fetus’s genetic makeup).

• Sample Collection: A blood sample is drawn from the mother, usually from 10 weeks gestation onward, when fetal fraction is sufficient for analysis 1 5 14.
• DNA Extraction and Sequencing: The laboratory isolates cfDNA and uses sequencing or probe-based methods to quantify specific chromosomes or segments 1 3 7.
• Bioinformatic Analysis: Algorithms compare the proportion of DNA fragments from each chromosome to expected values, flagging any over- or under-representation that might indicate aneuploidy 1 3 14.

Types of NIPT

Standard NIPT

• Screens for trisomy 21, 18, 13, and sometimes sex chromosome abnormalities.
• High sensitivity and specificity, especially for trisomy 21 2 3 8 10 12 14.

Expanded NIPT (NIPT-Plus)

• Includes screening for microdeletions, microduplications, and other rare chromosomal abnormalities.
• Positive predictive value (PPV) is lower for rare conditions; confirmatory testing is essential 4 13.

Technological Advances

• Newer assays (e.g., Vanadis) aim to reduce costs and improve accuracy, facilitating broader access in various healthcare settings 7.

Accuracy, Limitations, and “No-Call” Results

• Sensitivity and Specificity: NIPT is highly sensitive (over 99% for Down syndrome) and specific for common trisomies, but less so for rare chromosomal changes 2 3 8 10 12 14.
• Positive Predictive Value (PPV): Varies by condition and maternal age. For trisomy 21, PPV can be 70–90%; for other conditions, it may be lower 8 13 14.
• No-Call Results: Occasionally, the test cannot provide a result (e.g., due to low fetal fraction or technical issues). “No-call” rates are typically under 1%, but may require a repeat test or alternative screening 10 14.

When Is NIPT Recommended?

• All Pregnant Women: Increasingly offered to all, regardless of age or risk factors.
• Higher-Risk Pregnancies: Especially recommended for women over 35, those with abnormal first-trimester screens, or personal/family history of chromosomal disorders 12.
• Global Variations: Guidelines and access differ by country, with some regions prioritizing high-risk pregnancies and others offering universal screening 1 12.

Nipt Test Results & Follow-Up

Receiving NIPT results can be a pivotal moment in pregnancy. Understanding what the results mean and the appropriate follow-up steps is vital for informed choices and optimal care.

Table 3: Interpreting NIPT Results and Typical Next Steps

Interpreting NIPT Results

NIPT is a screening test, not a diagnostic tool. This means:

• Low-Risk Result: Indicates a low likelihood of the targeted chromosomal abnormalities. However, it does not completely rule out all genetic conditions or guarantee a healthy baby. False negatives are rare but possible 1 5 8 14.
• High-Risk Result: Suggests a high probability of a specific chromosomal abnormality. Confirmatory diagnostic testing (such as amniocentesis or CVS) is necessary before making any irreversible decisions 2 3 4 10 14.

Accuracy and Predictive Value

• For Down syndrome (trisomy 21), sensitivity and specificity exceed 99%, with positive predictive values (PPVs) often above 80%, especially in older women 2 8 12 14.
• For trisomy 18 and 13, sensitivity and specificity remain high, though PPVs may be lower due to rarity 8 12 14.
• For rare chromosomal abnormalities and microdeletions, PPV is substantially lower; false positives are more common 4 13.

Causes of Discordant (False Positive/Negative) Results

False positives and negatives can occur for several biological reasons:

• Placental mosaicism: The placenta’s DNA may differ from the fetus.
• Maternal chromosomal anomalies or cancer: Rarely, maternal health issues can affect results.
• Vanishing twin: Residual DNA from a twin lost early in pregnancy can lead to errors 6 9 11.

Incidental and Unexpected Findings

Occasionally, NIPT can identify maternal conditions, such as previously undiagnosed cancers, when multiple chromosomal abnormalities are detected in the mother’s blood. In such cases, referral for further clinical evaluation is recommended 9 11.

Follow-Up Actions

After a Low-Risk Result:

• Continue standard prenatal care.
• No further action required unless other clinical concerns arise 1 5 8 10.

After a High-Risk Result:

• Referral for genetic counseling.
• Offer and discuss confirmatory diagnostic procedures (amniocentesis/CVS).
• Ultrasound examination may provide additional information 1 2 3 10 14.

After a No-Call Result:

• Consider repeating the test or using alternative screening/diagnostic methods 10 14.

After an Incidental Finding:

• Multidisciplinary follow-up, including oncology if maternal malignancy is suspected 9 11.

The Importance of Genetic Counseling

Every NIPT result—especially those indicating increased risk—should be accompanied by genetic counseling. This ensures families understand the meaning, limitations, and next steps, supporting informed and compassionate care 1 10.

Conclusion

NIPT has become a transformative tool in prenatal screening, offering unparalleled accuracy and safety for identifying common chromosomal disorders. However, it is not a diagnostic test and must be interpreted with care, always in the context of comprehensive counseling and follow-up options.

Key Takeaways:

• NIPT screens for major chromosomal abnormalities (trisomies 21, 18, 13, and sex chromosome aneuploidies) using maternal blood, with high sensitivity and specificity 1 2 3 10 14.
• The test is non-invasive, reducing the need for riskier diagnostic procedures 1 3 5 10.
• Expanded NIPT can detect additional genetic disorders, but with lower predictive value—confirmatory testing is essential 4 13.
• Results are classified as low-risk, high-risk, or occasionally no-call; all high-risk and ambiguous results require follow-up and genetic counseling 1 2 3 4 10 14.
• Rarely, NIPT may reveal maternal health issues, such as cancer, which necessitate specialized follow-up 9 11.
• Genetic counseling is crucial at every step to ensure families make informed, supported decisions 1 10.

By understanding the purpose, process, and implications of NIPT, expectant families and healthcare providers can navigate prenatal screening with greater confidence and clarity.