What are the indications for Non-Invasive Prenatal Test (NIPT)?

Indications for Non-Invasive Prenatal Testing (NIPT)

The American College of Medical Genetics and Genomics (ACMG) strongly recommends NIPT for ALL pregnant patients with singleton pregnancies, regardless of maternal age or risk status, for screening of fetal trisomies 21,18, and 13. 1, 2

Universal Screening Recommendation

The paradigm has fundamentally shifted from risk-based to universal screening:

• NIPT should be offered to all pregnant women, not just those traditionally considered "high-risk" (such as maternal age ≥35 years or abnormal serum screening results). 1, 2
• All pregnant patients must be made aware of NIPT availability and its superior sensitivity for detecting common trisomies. 1
• NIPT with appropriate pre- and post-test counseling should be accessible to all pregnant patients to address existing healthcare disparities. 1

Specific Clinical Indications

Singleton Pregnancies

NIPT is indicated for screening of:

• Trisomy 21 (Down syndrome) - detection rate 98.8% with only 0.04% false-positive rate. 1, 2, 3
• Trisomy 18 (Edwards syndrome) - detection rate 98.83% with 0.07% false-positive rate. 1, 2
• Trisomy 13 (Patau syndrome) - detection rate 92.85% with 0.04% false-positive rate. 1, 2
• Sex chromosome aneuploidies (Turner syndrome, Triple X, Klinefelter syndrome, 47,XYY) - overall detection rate 99.6% with 99.8% specificity. 2, 3

Twin Pregnancies

NIPT is strongly recommended for all twin gestations, as it demonstrates equivalent performance to singleton pregnancies and significantly outperforms traditional screening methods. 2, 4

• Trisomy 21 sensitivity: 98.2% with 99.9% specificity. 4, 3
• Trisomy 18 sensitivity: 90% with 99.95% specificity. 4
• Trisomy 13 sensitivity: 80% with 99.93% specificity. 4

Timing of Testing

• NIPT can be performed any time during gestation after 10 weeks when fetal fraction is adequate (10-15% of cell-free DNA is placental origin). 1, 4, 3
• This represents a significant advantage over traditional screening, which requires specific gestational age windows and multiple visits. 1

Relative Contraindications

NIPT should NOT be performed in the following circumstances:

• Known vanishing twin gestation - the high incidence of aneuploidy in early embryonic demise may affect correct interpretation of the living twin's status. 1, 4
• Known maternal malignancy - somatic genomic aberrations in cancerous cells may be detected but cannot be ascribed to fetal or maternal origin. 1, 4

Critical Clinical Caveats

Understanding Test Limitations

• NIPT is a screening test, NOT diagnostic - all positive results require confirmatory invasive testing (amniocentesis or chorionic villus sampling). 4, 3
• Approximately 1% of samples result in "no-call" results, most commonly due to insufficient fetal fraction. 1, 4, 3
• Repeat testing provides results 75-80% of the time. 1
• The American College of Obstetricians and Gynecologists recommends offering diagnostic testing to individuals with no-call results. 1

Positive Predictive Values Vary by Condition

While NIPT has excellent sensitivity, positive predictive values differ:

• Trisomy 21: 91.8% PPV 1
• Trisomy 18: 65.8% PPV 1
• Trisomy 13: 37.2% PPV 1
• Sex chromosome aneuploidies have lower PPVs: 29.5% for Turner syndrome, 54% for Triple X, 74% for Klinefelter syndrome, 74.5% for 47,XYY. 2, 3

Factors Affecting Test Performance

• High maternal BMI increases test failure rates up to 20% due to low fetal fraction. 4, 3
• Certain anticoagulants, autoimmune disorders, and obesity are associated with higher no-call rates. 1

Superiority Over Traditional Screening

NIPT vastly outperforms traditional screening methods:

• Traditional first-trimester combined screening (NT + biochemistry): 82-87% detection rate with 3-5% false-positive rate. 1
• Traditional second-trimester quad screen: 81% detection rate with higher false-positive rates. 1
• Sequential screening (both trimesters): 94-96% detection rate but requires multiple visits and longer time to results. 1

In contrast, NIPT achieves 98.8% detection for trisomy 21 with only 0.04% false-positive rate in a single blood draw. 1, 2

Essential Counseling Requirements

• Pre-test counseling must emphasize that NIPT is screening, not diagnostic. 1, 2
• Post-test counseling is critical, especially for sex chromosome abnormalities given their variable phenotypes and lower PPVs. 2
• NIPT cannot replace ultrasound for structural anomaly detection. 4
• Patients must understand that positive results require invasive confirmation before making reproductive decisions. 4, 3