Role of Non-Invasive Prenatal Testing (NIPT) in Pregnancy
NIPT is strongly recommended as a superior screening method for detecting common trisomies (13,18, and 21) in pregnancy, with high detection rates (99.6% for Trisomy 21) and low false-positive rates (0.04%), but requires diagnostic confirmation of positive results through invasive testing. 1
What is NIPT?
NIPT is a blood test that analyzes cell-free fetal DNA in maternal circulation to screen for chromosomal abnormalities. Key features include:
- Analyzes placental DNA circulating in maternal blood (not truly fetal DNA) 2
- Can be performed after 9-10 weeks of pregnancy 3
- Non-invasive procedure with no risk of pregnancy loss 2
Recommended Applications
NIPT is recommended for screening:
- Common autosomal trisomies:
- Trisomy 21 (Down syndrome)
- Trisomy 18 (Edwards syndrome)
- Trisomy 13 (Patau syndrome)
- Sex chromosome abnormalities (SCAs):
- Monosomy X (Turner syndrome)
- XXX, XXY, XYY syndromes 1
Test Performance
NIPT significantly outperforms traditional screening methods:
| Trisomy | Sensitivity | Specificity |
|---|---|---|
| 21 | 99.6% | 99.8% |
| 18 | 97.7% | 99.9% |
| 13 | 96.1% | 99.9% |
Overall detection rate for sex chromosome abnormalities: 99.6% with 99.8% specificity 1
Important Limitations
Requires diagnostic confirmation: All positive NIPT results must be confirmed through invasive diagnostic testing (amniocentesis or CVS) 1
Test failures occur: Approximately 1-6% of samples fail to provide results (no-call results), which may be associated with higher rates of chromosomal abnormalities 1, 2
Limited scope: NIPT primarily targets common trisomies, which account for only ~50% of all chromosomal abnormalities 2
Not diagnostic: NIPT remains a screening test that provides risk estimation, not a definitive diagnosis 2
Does not screen for neural tube defects: Separate screening is required 1
Clinical Impact
- Reduces the number of invasive diagnostic procedures by 31-79% depending on population and indications 4
- Has changed the landscape of prenatal diagnosis worldwide 5
- Particularly valuable for twin gestations, with 98.2% sensitivity for T21 and 99.9% specificity 1
Pre-test and Post-test Counseling Requirements
Pre-test counseling must include:
- Optional nature of testing
- Conditions that can and cannot be detected
- Possible results and their implications
- Positive and negative predictive values
- Need for confirmation of abnormal results 1
Post-test counseling should emphasize:
- For negative results: risk reduction but not elimination
- For positive results: positive predictive values, balanced description of the condition, and recommendation for diagnostic confirmation 1
Special Considerations
Rare autosomal trisomies (RATs): The American College of Medical Genetics and Genomics (ACMG) states there is insufficient evidence to recommend NIPT for identifying RATs (trisomies other than 13,18,21, X, or Y) 4
Copy number variants (CNVs): Limited evidence for routine use at the population level, though may be offered based on pregnancy or family history with appropriate genetic counseling 4
Twin pregnancies: NIPT is strongly recommended over traditional methods 1
No-call results: Consider diagnostic testing as these may be associated with higher rates of chromosomal abnormalities 1
Implementation Considerations
- Implementation varies by country based on healthcare systems and existing screening programs 6
- In countries with state-sponsored screening, NIPT is often offered to "high-risk" women
- In market-based healthcare systems, multiple versions of NIPT covering a wider range of conditions may be available directly to consumers 6
NIPT represents a significant advance in prenatal screening technology that balances high detection rates with non-invasive collection, but proper counseling about its limitations and the need for diagnostic confirmation of positive results is essential to avoid providing patients with a false sense of security.