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Introduction
NIPT (Non-Invasive Prenatal Testing) has garnered attention as a prenatal screening method during pregnancy. By analyzing fetal DNA present in the mother’s blood, it enables early detection of various chromosomal abnormalities. Compared to traditional invasive tests such as amniocentesis or chorionic villus sampling, NIPT poses less risk to both the mother and fetus and offers high accuracy, making it a preferred option for many expectant mothers.
This article provides a detailed explanation of the types of chromosomal abnormalities detectable by NIPT, how the test works, its accuracy and limitations, and important considerations when choosing to undergo testing.
1. What is NIPT?
NIPT analyzes cell-free fetal DNA (cfDNA) circulating in the maternal blood to assess the likelihood of chromosomal abnormalities in the fetus.
Fetal DNA can be detected from early pregnancy, and testing is generally conducted from the 10th week of gestation. A key feature of NIPT is that it carries almost no risk of miscarriage, unlike invasive procedures.
How NIPT Works:
- Blood sample collection from the mother
- Extraction of cfDNA
- Chromosomal analysis using Next-Generation Sequencing (NGS)
- Evaluation of chromosomal number abnormalities
2. Types of Chromosomal Abnormalities Detectable by NIPT
NIPT primarily detects numerical chromosomal abnormalities (trisomies and monosomies). Below are the most common conditions:
2‑1. Trisomy 21 (Down Syndrome)
This is the most common chromosomal abnormality, caused by an extra copy of chromosome 21.
Physical traits include short stature, flat facial profile, upslanted eye fissures, and intellectual disability.
NIPT can detect this condition with over 99% sensitivity and specificity.
Reference: Bianchi DW et al., N Engl J Med, 2014;370:799‑808
2‑2. Trisomy 18 (Edwards Syndrome)
Trisomy 18 results from an extra chromosome 18. It is often associated with severe congenital heart and kidney defects, developmental delays, and typically short life expectancy after birth.
Detection sensitivity is around 97–99% and specificity is approximately 99%.
Reference: Palomaki GE et al., Genet Med, 2012;14:296‑305
2‑3. Trisomy 13 (Patau Syndrome)
Caused by an extra chromosome 13, this condition involves multiple congenital anomalies and typically short survival.
Detection sensitivity is approximately 90–95%, with specificity near 99%.
2‑4. Sex Chromosome Abnormalities
NIPT can also detect abnormalities in the sex chromosomes (X and Y).
Examples include:
- Turner Syndrome (45,X): Female missing one X chromosome; may have short stature, ovarian dysfunction
- Klinefelter Syndrome (47,XXY): Male with an extra X chromosome; tall stature, infertility, and learning difficulties
- Triple X Syndrome (47,XXX): Female with an extra X chromosome; may have mild intellectual and reproductive issues
- Jacobs Syndrome (47,XYY): Male with an extra Y chromosome; typically mild physical and cognitive effects
Reference: Norton ME et al., N Engl J Med, 2015;372:1589‑1597
3. Detection of Microdeletions and Duplications
Advancements in technology have enabled the detection of certain microdeletions and microduplications, in addition to common trisomies and monosomies.
For example, 22q11.2 deletion syndrome (DiGeorge syndrome) involves cardiac defects, immune system abnormalities, and intellectual disabilities, and can now be screened via NIPT in some settings.
Reference: Liang D et al., Prenat Diagn, 2018;38:789‑797
However, detection of microabnormalities has lower sensitivity and higher false-positive rates. Positive results should be followed by confirmatory testing (amniocentesis or chorionic villus sampling).
4. Accuracy and Limitations of NIPT
4‑1. Accuracy
- Trisomy 21: Sensitivity >99%, Specificity >99%
- Trisomy 18: Sensitivity ~97–99%, Specificity ~99%
- Trisomy 13: Sensitivity ~90–95%, Specificity ~99%
- Sex Chromosome Abnormalities: Sensitivity 85–95%, Specificity ~99%
Reference: Gil MM et al., Ultrasound Obstet Gynecol, 2015;45:530‑539
4‑2. Limitations
- False Positives/Negatives:
Maternal cfDNA can affect results, especially if the mother has chromosomal abnormalities or tumors. - Detection Limits:
Microdeletions/duplications under 5–10 Mb are difficult to detect. - Not a Diagnostic Test:
NIPT is a screening test. Positive results require confirmatory diagnostic testing.
5. When and How to Take NIPT
- Consult with your OB-GYN after 10 weeks of pregnancy
- Blood collection
- Sample sent to a lab
- Results provided (usually within 1–2 weeks)
- If positive, discuss confirmatory testing with your doctor
6. Key Considerations When Choosing NIPT
- Understand that NIPT is a screening, not a diagnostic test
- Detection sensitivity for sex chromosome and microdeletion abnormalities is relatively lower
- The types of chromosomal abnormalities tested vary by institution
- Genetic counseling is recommended due to the potential psychological impact of results
7. Summary So Far
NIPT is a highly accurate and low-risk screening method that allows early detection of major chromosomal abnormalities such as Trisomy 21, 18, and 13. The detection scope has expanded in recent years to include microdeletions.
However, it remains a screening—not a diagnostic—tool, and its accuracy has limits, particularly for sex chromosome and microdeletion abnormalities. Proper use in consultation with a doctor or genetic counselor can help enhance prenatal care options and support safe pregnancy management.
8. Latest Advances and Expanded Scope in NIPT
8‑1. Use of Microarray Analysis
With microarray technology, NIPT can detect some microdeletions/duplications previously undetectable.
Examples include:
- 22q11.2 Deletion Syndrome
- 1p36 Deletion Syndrome
- 15q11.2 Deletion Syndrome (Prader-Willi, Angelman Syndromes)
These have lower sensitivity and specificity; positive results require confirmatory testing.
8‑2. Improved Detection of Sex Chromosome Abnormalities
NGS has improved the detection accuracy of conditions like Turner and Klinefelter syndromes. However, due to the risk of false positives, counseling and confirmatory testing remain essential.
9. Statistics and Usage in Japan
Since its introduction in Japan in 2013, the number of NIPT facilities has increased, with over 100,000 tests performed annually.
Initially focused on advanced maternal age (35+), NIPT is now used across all age groups.
Positive predictive value (PPV) for Down syndrome varies by age and gestational week:
- Over age 35: ~90%
- Around age 30: ~60–70%
Reference: Akolekar R et al., Ultrasound Obstet Gynecol, 2015;45:530‑539
10. Ethical Considerations of NIPT
While NIPT provides valuable genetic information, ethical and psychological considerations are important:
- Positive results indicate possibility, not confirmation
- The information may cause emotional stress for families
- Some chromosomal abnormalities have only mild symptoms
- Sex chromosome abnormalities may influence prenatal decisions
Genetic counseling is recommended to explain test limitations, interpret results, and consider next steps.
11. Cost and Insurance Coverage
In Japan, NIPT typically costs around ¥150,000–¥200,000.
Currently, it is not covered by health insurance and is paid out-of-pocket, even for high-risk pregnancies.
Be aware of additional costs such as counseling and follow-up diagnostics.
12. How to Choose the Right NIPT
- Clarify your purpose: Screening for major trisomies only? Or include microdeletions?
- Understand test accuracy: High for Trisomy 21; lower for sex chromosomes and microdeletions
- Receive counseling: Prepare for emotional impact and future decisions
- Be ready for follow-up testing: Positive results should be confirmed via diagnostic testing
13. Conclusion
NIPT is a revolutionary prenatal screening tool with high accuracy and minimal risk to both mother and fetus. Its scope now includes sex chromosome and microdeletion abnormalities.
However, it is not a diagnostic test, and positive results require further confirmation. Understanding its limitations and receiving appropriate counseling ensures better decision-making and peace of mind during pregnancy management.
