What is the recommended approach for aneuploidy screening in twin pregnancy?

Aneuploidy Screening in Twin Pregnancies

First trimester combined screening with nuchal translucency (NT) measurement and maternal serum markers is the recommended approach for aneuploidy screening in twin pregnancies, with specific considerations based on chorionicity. 1

Screening Approach Based on Chorionicity

Dichorionic Twins

• NT measurement plus maternal serum markers (PAPP-A and free beta-hCG or intact hCG) provides detection rates close to those in singletons with sensitivities over 85% 1
• Individual risk can be calculated for each fetus (fetus-specific risk) 1, 2
• Standard 3mm threshold for increased NT applies, same as in singletons 1
• False-positive rates are reduced when biochemistry is added to NT measurement 3

Monochorionic Twins

• First trimester combined screening provides similar detection rates to singletons but with higher false-positive rates 1
• Risk calculation uses the average NT measurement of both twins (pregnancy-specific risk) 1, 2
• NT measurements are typically higher in monochorionic twins compared to dichorionic twins 1
• All monochorionic twins should undergo fetal echocardiography regardless of NT measurements due to 2% risk of congenital heart disease (5% in twin-twin transfusion syndrome) 1

Important Clinical Considerations

1. Chorionicity determination is critical and should be performed by ultrasound in the first trimester for all twin pregnancies 2

2. NT measurement advantages in twins:

   • Allows individual assessment of each fetus 1
   • Distribution of measurements similar to singletons 1
   • Particularly useful because maternal serum markers alone cannot identify which fetus is at risk 1

3. Serum marker limitations:

   • Serum markers reflect both pregnancies and are averaged, creating interpretation challenges 1
   • Free beta-hCG is likely superior to intact hCG for Down syndrome screening, though many US programs use intact hCG due to limited access 1, 4

4. Cell-free DNA (cfDNA) considerations:

   • Should be considered a first-line approach when available 5
   • Superior to serum and ultrasound-based tests according to meta-analyses 6
   • May provide additional information on zygosity 6
   • May have limitations in certain scenarios such as vanishing twins 5

5. Diagnostic testing:

   • When non-invasive screening is available, maternal age alone should not be an indication for invasive testing 2
   • Both amniotic sacs should be sampled during amniocentesis in monochorionic twins unless monochorionicity is confirmed before 14 weeks and fetuses appear concordant for growth and anatomy 2
   • For CVS in non-monochorionic pregnancies, a combination of transabdominal and transcervical approaches or transabdominal-only approach minimizes sampling errors 2

Special Circumstances

• Increased NT (≥3.5mm): Even with low-risk screening results or normal karyotype, warrants detailed anatomic ultrasound and echocardiogram 1

• NT discordance in monochorionic twins: NT discordance >20% associated with >30% risk of severe twin-twin transfusion syndrome and early fetal death 1

• Crown-rump length discrepancy: >10% discrepancy associated with almost double the risk of developing twin-twin transfusion syndrome 1

Clinical Algorithm

1. Determine chorionicity by first-trimester ultrasound
2. Perform NT measurement at 11-14 weeks gestation
3. Obtain maternal serum markers (PAPP-A and hCG)
4. Calculate risk based on chorionicity:
   • Dichorionic: fetus-specific risk
   • Monochorionic: pregnancy-specific risk using average NT
5. Consider cfDNA screening if available
6. Offer invasive testing if high-risk result obtained
7. Schedule detailed anatomy scan and fetal echocardiography if increased NT identified
8. For monochorionic twins, schedule fetal echocardiography regardless of NT results

By following this structured approach to aneuploidy screening in twin pregnancies, clinicians can optimize detection rates while minimizing unnecessary invasive procedures.