What is the sensitivity of Non-Invasive Prenatal Testing (NIPT)?

Sensitivity of Non-Invasive Prenatal Testing (NIPT)

Overall Performance for Common Trisomies

NIPT demonstrates exceptionally high sensitivity for detecting fetal chromosomal abnormalities, with 99.3% sensitivity for trisomy 21 (Down syndrome), 97.4% for trisomy 18 (Edwards syndrome), and 97.4% for trisomy 13 (Patau syndrome) in singleton pregnancies. 1

Trisomy 21 (Down Syndrome)

• Sensitivity: 98.8-99.3% with a false-positive rate of only 0.04% 2, 1
• This represents a detection rate superior to all traditional screening methods 3
• Specificity reaches 99.9% across multiple studies 1

Trisomy 18 (Edwards Syndrome)

• Sensitivity: 97.4-98.83% with a false-positive rate of 0.07% 2, 1
• In twin pregnancies, sensitivity decreases to 90% (95% CI = 67.6%-97.5%) with specificity of 99.95% 3, 4

Trisomy 13 (Patau Syndrome)

• Sensitivity: 92.85-97.4% with a false-positive rate of 0.04% 2, 1
• In twin pregnancies, sensitivity drops to 80% (95% CI = 30.9%-97.3%) with specificity of 99.93% 3, 4

Sex Chromosome Aneuploidies

NIPT shows an overall detection rate of 99.6% (95% CI = 94.8%-100%) for sex chromosome aneuploidies with 99.8% specificity. 3, 2

However, positive predictive values vary significantly by condition:

• Monosomy X (Turner syndrome): 29.5% PPV (95% CI = 22.7%-37.4%) 3, 2
• Triple X syndrome (47,XXX): 54% PPV (95% CI = 40.6%-66.8%) 3, 2
• Klinefelter syndrome (47,XXY): 74% PPV (95% CI = 59.5%-84.7%) 3, 2
• 47,XYY syndrome: 74.5% PPV (95% CI = 58.4%-85.8%) 3, 2

The lower PPV for monosomy X reflects higher rates of placental mosaicism and maternal mosaicism that would not be detected through amniocentesis 3

Performance in Twin Pregnancies

NIPT maintains excellent performance in twin gestations, with sensitivity of 98.2% for trisomy 21, though slightly reduced for trisomies 18 and 13. 4, 2

• Trisomy 21: 98.2% sensitivity (95% CI = 88.2%-99.7%) and 99.9% specificity 4
• Trisomy 18: 90% sensitivity (95% CI = 67.6%-97.5%) and 99.95% specificity 4
• Trisomy 13: 80% sensitivity (95% CI = 30.9%-97.3%) and 99.93% specificity 4

This represents a 9% reduction in sensitivity for trisomy 21,28% reduction for trisomy 18, and 22% reduction for trisomy 13 compared to singleton pregnancies 1

Critical Factors Affecting Sensitivity

Test Failure and No-Call Results

• Approximately 1% of samples result in "no-call" results, most commonly due to insufficient fetal fraction 3, 4
• Repeat testing provides results in 75-80% of cases 3
• High maternal BMI increases test failure rates up to 20% due to low fetal fraction 4

Timing Considerations

• NIPT should be performed after 10 weeks gestation when fetal fraction is adequate (10-15% of cell-free DNA is placental origin) 4
• Sensitivity is lower in first trimester testing compared to later gestational ages 1

Absolute Contraindications

• Known vanishing twin or triplet: NIPT should NOT be performed due to risk of false-positive results or test failure 4, 5
• Known maternal malignancy: Relative contraindication due to potential somatic genomic aberrations 4, 2

Comparison to Traditional Screening

NIPT dramatically outperforms traditional screening methods:

• Traditional second trimester biochemistry: 63% detection rate with 10.8% false-positive rate 3, 4
• First trimester NT with biochemistry: 75% detection rate with 9% false-positive rate 3, 4
• NIPT for trisomy 21: 98.8-99.3% detection rate with 0.04% false-positive rate 2

This translates to requiring only 1.1-2 amniocentesis procedures to confirm one case of trisomy 21 with NIPT versus 28-45 procedures with traditional screening 3

Essential Clinical Caveats

• NIPT is a screening test, not diagnostic - all positive results require confirmatory invasive testing with amniocentesis or chorionic villus sampling 4, 6
• False-positive results occur in 0.2-1% of cases, and false-negative results are possible 7
• NIPT cannot replace ultrasound for structural anomaly detection 4
• Some pregnancies with no-call results have higher rates of fetal chromosome disorders, though this association is not universally confirmed 3