Effectiveness of NIPT in Risk Assessment for Down Syndrome

Introduction

Assessing the risk of fetal chromosomal abnormalities during pregnancy is a critical concern for expectant mothers. Among these, Down syndrome (Trisomy 21) draws the most attention. It results from the presence of an extra 21st chromosome and may be associated with physical characteristics, developmental delays, and intellectual disabilities. In recent years, Non-Invasive Prenatal Testing (NIPT) has been shown to offer high accuracy in assessing the risk of Down syndrome. This article explains the fundamentals, effectiveness, comparison with conventional methods, clinical applications, and points to note about NIPT.

1. What is Down Syndrome

Down syndrome, medically termed “Trisomy 21,” is a chromosomal abnormality. Humans normally have 46 chromosomes, but the presence of a third copy of chromosome 21 leads to this condition. Main features include:

• Distinct facial features (upward-slanting eyes, flat nasal bridge, etc.)
• Developmental delays and intellectual disabilities
• Increased risk of complications such as congenital heart defects

The risk of Down syndrome increases with maternal age, especially in women over 35. However, younger women are not risk-free, so accurate risk assessment is essential.

2. What is NIPT

NIPT is a test that analyzes fetal-derived cell-free DNA (cfDNA) present in maternal blood to assess the risk of chromosomal abnormalities. Unlike invasive procedures like amniocentesis or chorionic villus sampling, NIPT requires only a blood draw, making it extremely low-risk for both mother and fetus.

2‑1. How It Works

NIPT detects an excess or shortage of specific chromosomes by analyzing cell-free fetal DNA (cffDNA) in the mother’s blood. It mainly targets:

• Trisomy 21 (Down syndrome)
• Trisomy 18 (Edwards syndrome)
• Trisomy 13 (Patau syndrome)

The test is increasingly used to screen for sex chromosome abnormalities and microdeletion syndromes as well.

2‑2. When It’s Performed

NIPT can be conducted from week 10 of pregnancy. Early detection allows for better pregnancy management and planning of any necessary follow-up testing.

3. Effectiveness of NIPT

Multiple clinical studies have reported that NIPT demonstrates extremely high sensitivity and specificity in Down syndrome screening.

• Sensitivity: Nearly 99% or higher
   → Nearly all fetuses with Down syndrome will test positive.
• Specificity: Over 99%
   → The chance of a false positive in a healthy fetus is very low.

3‑1. Comparison with Conventional Tests

Traditional screening (e.g., maternal serum markers, ultrasound) typically shows 70–90% sensitivity and around 90% specificity. In contrast, NIPT has a much lower false positive rate and offers a more reliable screening option before considering invasive testing.

Reference: Bianchi DW et al., NEJM. 2014;370:799–808.

4. Clinical Significance of NIPT

4‑1. Safety for Mother and Fetus

Amniocentesis and CVS carry a 0.1–0.3% risk of miscarriage. Since NIPT is conducted through a blood sample, the risk of miscarriage is nearly zero, and the physical and psychological burden on the mother is significantly reduced.

4‑2. Contribution to Pregnancy Management

Getting early NIPT results helps with timely planning. A positive result may lead to confirmatory testing and coordinated care with the medical team. A negative result provides psychological reassurance and supports the decision to continue the pregnancy with confidence.

5. Limitations and Considerations

5‑1. Not a Diagnostic Test

NIPT is a screening test, not a diagnostic tool. A positive result must be followed by invasive diagnostic procedures (like amniocentesis).

5‑2. Risk of False Negatives / Positives

In cases where the fetal fraction (percentage of fetal DNA in the mother’s blood) is low, the results may be less accurate. Detection may also be less reliable in multiple pregnancies or specific chromosomal abnormalities.

5‑3. Ethical and Psychological Concerns

Results can influence critical decisions during pregnancy. Genetic counseling is essential for pre-test education and post-test support, helping patients understand the implications of their results.

6. Availability and Cost of NIPT

In Japan, NIPT has been available clinically since 2013 and is now offered in many medical institutions. The cost is typically ¥150,000–200,000, depending on the provider. It is not covered by national insurance and is considered an out-of-pocket expense, conducted based on the doctor’s discretion and patient request.

7. Summary So Far

NIPT is a highly accurate and low-risk screening method for assessing Down syndrome risk, offering major advantages over traditional methods. Because it can be performed early in pregnancy, it allows for timely decision-making, mental relief for expectant mothers, and better pregnancy management by healthcare providers. However, since it is not diagnostic, positive results require confirmatory testing and appropriate genetic counseling.

With ongoing improvements in accuracy and an expanding scope of use, NIPT is expected to become a central tool in prenatal screening.

8. Importance of Genetic Counseling

Genetic counseling is highly recommended for those undergoing NIPT. Counseling provides:

• Clear explanation of NIPT’s principles, accuracy, and limitations
• Support for decision-making based on test results
• Guidance for confirmatory testing if necessary
• Information on medical and social support resources before and after birth

Counseling helps patients understand their test results and reduces anxiety. If a positive result is received, it’s vital for families to understand their options regarding pregnancy continuation, delivery, and child-rearing.

9. Support for Children with Down Syndrome

NIPT not only helps with prenatal assessment, but also contributes to planning postnatal support. Children with Down syndrome can live high-quality lives with proper care and intervention:

• Early diagnosis and treatment of heart or gastrointestinal issues
• Physical, occupational, and speech therapy
• Special education and community-based social support

Identifying the risk prenatally makes it easier to prepare the necessary medical, educational, and social frameworks.

10. Future Outlook

Currently, NIPT focuses on detecting major trisomies (21, 18, 13), but future advancements may expand its application to:

• Sex chromosome and microdeletion syndromes
• Multiple pregnancies and IVF pregnancies
• Personalized prenatal risk management

With improvements in analysis technology, we expect reduced false positives and negatives, and broader use among low-risk pregnancies.

11. Conclusion

NIPT offers superior accuracy and safety in prenatal risk assessment for Down syndrome compared to traditional screening methods. While it is not a diagnostic tool, its ability to identify risk early contributes significantly to pregnancy care, postnatal planning, and peace of mind for expectant mothers. Combined with genetic counseling, it empowers informed decisions and better health outcomes.

NIPT is poised to become the core method for prenatal screening, expanding its reach as technology continues to evolve. It is an essential tool in delivering personalized, accurate, and safe information for pregnancy management and family planning.

References

Gil MM et al. Implementation of NIPT in clinical practice: Large-scale study. Ultrasound Obstet Gynecol. 2015.

Bianchi DW et al. DNA sequencing versus standard prenatal aneuploidy screening. N Engl J Med. 2014.

Norton ME et al. Cell-free DNA analysis for trisomy. N Engl J Med. 2015.