What is the role of Non-Invasive Prenatal Testing (NIPT) in twin pregnancies?

NIPT in Twin Pregnancies: Clinical Role and Performance

NIPT should be offered to all women with twin pregnancies for screening of trisomy 21,18, and 13, as it demonstrates equivalent performance to singleton pregnancies and significantly outperforms traditional screening methods. 1

Primary Recommendation for Trisomy Screening

The American College of Medical Genetics and Genomics (ACMG) strongly recommends NIPT over traditional screening methods for trisomy screening in twin gestations. 1

Performance Characteristics in Twin Pregnancies

For Trisomy 21:

• Sensitivity: 98.2% (95% CI = 88.2%-99.7%) 1
• Specificity: 99.9% (95% CI = 99.8%-100%) 1
• These metrics are equivalent to singleton pregnancy performance 1, 2

For Trisomy 18:

• Sensitivity: 90% (95% CI = 67.6%-97.5%) 1
• Specificity: 99.95% (95% CI = 99.8%-100%) 1

For Trisomy 13:

• Sensitivity: 80% (95% CI = 30.9%-97.3%) 1
• Specificity: 99.93% (95% CI = 99.4%-100%) 1

Superiority Over Traditional Screening

Traditional screening methods perform poorly in twin pregnancies compared to NIPT: 1

• Second trimester biochemistry detects only 63% of trisomy 21 cases with a 10.8% false-positive rate 1
• First trimester nuchal translucency with biochemistry detects 75% with a 9% false-positive rate 1
• Traditional screening methods were generally not available for trisomy 13 screening in twins 1

Sex Chromosome Aneuploidy Screening

The ACMG recommendation for sex chromosome aneuploidy (SCA) screening is specific to singleton pregnancies only, with a strong recommendation based on high certainty of evidence. 1 The guidelines do not extend this recommendation to twin pregnancies, and available research shows significantly lower positive predictive values for SCA in twins. 3, 4

Critical Clinical Caveats

Vanishing Twin Syndrome

• NIPT should not be performed in pregnancies with a known vanishing twin, according to the American College of Obstetricians and Gynecologists 1
• The high incidence of aneuploidy in early embryonic demise can affect interpretation of the living twin's status 1
• If NIPT is performed despite this contraindication, patients must be counseled that accuracy may be significantly impacted 1

Maternal Malignancy

• Known maternal malignancy is a relative contraindication to NIPT 1
• Somatic genomic aberrations from cancerous cells may be detected but cannot be reliably attributed to fetal or maternal origin 1

Positive Predictive Value Considerations

• While sensitivity and specificity remain high in twins, the positive predictive value varies by condition 3, 4, 5
• Research data shows PPV of 100% for trisomy 21,75% for trisomy 18, but only 25% for sex chromosome abnormalities in twins 5
• All positive NIPT results require confirmatory diagnostic testing with amniocentesis or chorionic villus sampling 6, 4

Timing and Technical Factors

• NIPT should be performed after 10 weeks gestation when fetal fraction is adequate (10-15% of cell-free DNA is placental origin) 6
• In dizygotic twins, individual fetal fractions can be measured to ensure both values are satisfactory 7
• High maternal BMI is associated with low fetal fraction and may result in test failure in up to 20% of women 6
• Approximately 1% of samples result in "no-call" results, most commonly due to insufficient fetal fraction 6

Essential Pre- and Post-Test Counseling

Patients must understand: 4, 7

• NIPT is a screening test, not diagnostic 6, 4
• Positive results require invasive testing for confirmation 6, 4
• Chorionicity, mode of conception, and fetal fraction should be considered as influencing factors 4
• NIPT cannot replace ultrasound for structural anomaly detection 6