What are the implications and management options for a fetus with increased nuchal translucency (NT)?

Management of Increased Nuchal Translucency in Fetuses

A fetus with increased nuchal translucency (NT ≥3 mm) requires immediate genetic counseling, invasive diagnostic testing, and comprehensive follow-up monitoring due to significant risks of chromosomal abnormalities, structural defects, and adverse pregnancy outcomes. 1, 2

Definition and Clinical Significance

• Nuchal translucency is the hypoechoic space between the overlying skin and underlying soft tissues of the posterior cervical spine in the first-trimester fetus 2
• NT increases with crown-rump length, so gestational age must be considered when determining if a measurement is abnormal 2
• An increased NT is defined as ≥3 mm or above the 99th percentile for the crown-rump length 2
• Approximately one-third of fetuses with NT ≥3 mm will have chromosomal abnormalities, with half of these being trisomy 21 1, 2

Implications of Increased NT

Chromosomal Abnormalities

• About one-third of fetuses with NT thickness above 3 mm will have a chromosomal abnormality 1
• The risk of adverse pregnancy outcomes increases proportionally with the degree of NT enlargement 1
• Even with NT measurements between 2.5-2.9 mm, there is a significantly higher risk of aneuploidy (3.4%) compared to normal NT (1.4%) 3

Structural Defects

• In euploid fetuses (normal chromosomes) with increased NT, there remains an elevated risk of structural anomalies, particularly cardiac defects 1, 2
• The risk of major structural anomalies persists even in fetuses subsequently found to be euploid 1
• In euploid fetuses with NT ≥3 mm, there is an increased risk of congenital heart disease 1

Genetic Syndromes

• In euploid fetuses with NT ≥3 mm, 10% have genetic variants consistent with Noonan syndrome 1
• Cell-free fetal DNA screening only detects trisomy 21,18,13, and sex chromosome aneuploidies, but will miss other genetic causes of increased NT such as Noonan syndrome and 22q11.2 deletion syndrome 1
• Genetic syndromes with dysmorphic features and neurodevelopmental delay can occur in approximately 1.6% of fetuses with normal karyotype but increased NT 4

Pregnancy Loss

• There is an increased risk of intrauterine demise in fetuses with large nuchal translucencies, even without associated chromosomal or structural abnormalities 1
• The overall incidence of adverse pregnancy outcomes in chromosomally normal fetuses with increased NT is approximately 19%, with risk increasing proportionally to NT measurement 4
• Recent research shows that even fetuses with early increased NT (before 11 weeks) are at considerable risk of adverse outcomes 5

Management Algorithm

Immediate Management

1. Genetic counseling and invasive diagnostic testing should be promptly offered 1, 2

   • Studies show minimal benefit in waiting for maternal serum results 1
   • Chorionic villus sampling provides earlier definitive diagnosis 1

2. Consider cell-free fetal DNA screening 1

   • Supported by ACOG for women with NT ≥3 mm 1
   • Remember this only detects trisomy 21,18,13, and sex chromosome aneuploidies 1

3. Perform targeted genetic studies 1

   • Microarray analysis is recommended in all cases of increased NT 1
   • Testing for Noonan syndrome should be considered 1

Follow-up Ultrasound Evaluations

1. Early fetal anatomic survey 1

   • Can be performed at the time increased NT is identified 1
   • Provides opportunity for early detection of major malformations affecting brain, heart, abdominal wall, and limbs 1
   • Note that sensitivity at 11-14 weeks is only about 50% compared to 75% at 18-22 weeks 1, 2

2. Second trimester anatomic survey 1

   • Should be offered regardless of fetal DNA analysis results 1
   • More sensitive for detecting congenital anomalies than first-trimester ultrasound 1

3. Fetal echocardiography 1

   • NT ≥3 mm is an accepted indication for fetal echocardiography 1
   • Optimal timing is at 18-22 weeks of gestation 1
   • Early echocardiography at 11-14 weeks may also be performed but has limitations 1
   • A repeat fetal echocardiogram is recommended in the second trimester even if early evaluation was performed 1

Ongoing Monitoring

• Serial fetal surveillance should be added to routine prenatal care 1
• Periodic ultrasound examinations to monitor fetal growth and well-being are recommended 1
• The risk of adverse outcome persists even if NT normalizes after initial measurement 5

Special Considerations

Additional Ultrasound Techniques

• Transvaginal ultrasound may be advantageous in certain cases to more clearly identify the amnion and NT borders 1
• Doppler studies (tricuspid valve, ductus venosus) can provide additional risk assessment for aneuploidy and cardiac defects 1
• Significant tricuspid regurgitation and reversed a-waves in the ductus venosus are associated with chromosomal and cardiac defects 1

Prognosis After Normal Follow-up

• If the detailed ultrasound examination at around 20 weeks is normal, a favorable outcome can be expected with higher confidence 4
• However, even with normal follow-up ultrasound, a small risk of genetic syndromes with neurodevelopmental delay remains 4
• In cases with normalized NT and no ultrasound abnormalities at follow-up, the incidence of adverse outcome is still approximately 8.5% 5

Common Pitfalls to Avoid

• Do not rely solely on cell-free fetal DNA screening, as it will miss other genetic causes of increased NT 1
• Do not be falsely reassured by disappearance of nuchal thickening in follow-up scans 6
• Do not skip fetal echocardiography even if other evaluations are normal 1
• Do not assume normal outcome if NT normalizes; continued monitoring is still necessary 4, 5