What is the best prenatal genetic testing for a twin gestation that underwent spontaneous reduction from triplets?

Prenatal Genetic Testing for Triplets with Spontaneous Reduction to Twins

NIPT (noninvasive prenatal testing) should NOT be performed in this clinical scenario due to the vanishing triplet, and you should instead offer traditional first trimester combined screening (nuchal translucency + PAPP-A) or integrated screening, with diagnostic testing (CVS or amniocentesis) as an alternative. 1, 2

Critical Contraindication: Vanishing Twin/Triplet

The American College of Obstetricians and Gynecologists explicitly states that NIPT should not be performed in pregnancies with a known vanishing twin (which applies to your vanishing triplet scenario). 1 This is a firm contraindication, not merely a relative one. 2

Why This Matters

• The cell-free DNA from the demised/resorbed fetus(es) can persist in maternal circulation for weeks to months 3
• This residual DNA can lead to false-positive results if the vanished fetus had a chromosomal abnormality 3
• Conversely, it can dilute the fetal fraction and lead to test failure or inaccurate results 3
• The test cannot reliably distinguish which DNA comes from which fetus (surviving vs. vanished) 3

Recommended Alternative Screening Approaches

First-Line Option: Traditional Combined Screening

Offer integrated screening combining first and second trimester markers, which has 94-96% detection rates and maintains equivalent performance in twin pregnancies compared to singletons. 4 This includes:

• First trimester: Nuchal translucency (NT) measurement + PAPP-A 4
• Second trimester: Quad screen (AFP, unconjugated estriol, hCG, inhibin A) 4

This approach specifically maintains its screening performance in twin pregnancies, unlike some other methods. 4

Alternative: First Trimester Combined Screening Alone

If earlier results are desired, first trimester NT with biochemistry detects 75% of trisomy 21 cases with a 9% false-positive rate in twins. 1 While less sensitive than integrated screening, it provides earlier information for decision-making. 4

Second-Line Option: Diagnostic Testing

Given the limitations of screening in this scenario, consider offering diagnostic testing directly (chorionic villus sampling at 11-13 weeks or amniocentesis at 15+ weeks). 1 This is particularly appropriate if:

• The patient has high anxiety about accuracy 4
• There are other risk factors present 4
• The patient desires definitive results rather than screening 4

Important Counseling Points

Timing Considerations

• Earlier screening/diagnosis in twin pregnancies is particularly beneficial because diagnostic confirmation is more complex than in singletons 4
• If selective reduction is being considered for an affected twin, this is safer when performed in the first trimester 4
• Changes to delivery planning or transfer of care may need earlier implementation 4

What NOT to Do

• Do not proceed with NIPT despite its superior performance in uncomplicated twin pregnancies (98.2% sensitivity for T21) 1, because the vanishing triplet invalidates the test 1, 2
• Do not assume the vanished fetus DNA has cleared from maternal circulation without evidence 3
• Do not rely on second trimester biochemistry alone (only 63% detection rate with 10.8% false-positive rate) 1

Neural Tube Defect Screening

Regardless of aneuploidy screening choice, ensure maternal serum AFP screening is performed in the second trimester for neural tube defects, as this cannot be assessed by NIPT and remains important in twin pregnancies. 4

Future Consideration

If the patient desires NIPT-level accuracy for future pregnancies, this would be appropriate for uncomplicated twin gestations without vanishing multiples, as NIPT demonstrates equivalent performance to singleton pregnancies in that setting. 1, 2