What are the next steps for a pregnant patient with increased nuchal (nuchal translucency) lucency?

Management of Increased Nuchal Translucency

For any pregnant patient with nuchal translucency ≥3 mm, immediately offer genetic counseling and invasive diagnostic testing (CVS or amniocentesis), perform comprehensive ultrasound surveillance including mandatory fetal echocardiography at 18-22 weeks regardless of genetic testing results, and institute serial fetal monitoring throughout pregnancy. 1

Immediate Actions Required

Genetic Counseling and Diagnostic Testing

• Offer invasive diagnostic testing (chorionic villus sampling or amniocentesis) promptly to all patients with NT ≥3 mm, as approximately one-third of these fetuses will have chromosomal abnormalities, with half being trisomy 21 1, 2
• Perform chromosomal microarray analysis in all cases of increased NT, as this is recommended for comprehensive genetic evaluation beyond standard karyotyping 1
• Consider cell-free fetal DNA screening as an adjunctive test, though recognize it only detects trisomies 21,18,13, and sex chromosome aneuploidies while missing other genetic causes like Noonan syndrome and 22q11.2 deletion syndrome 1, 3

Important Caveat on Genetic Testing

Cell-free DNA screening has limitations—it will miss 10% of euploid fetuses with NT ≥3 mm who have genetic variants consistent with Noonan syndrome, as well as other structural and genetic abnormalities that NT screening can identify 1, 3

Ultrasound Surveillance Protocol

First Trimester Evaluation

• Perform an early fetal anatomic survey at the time increased NT is identified, which provides opportunity for early detection of major malformations affecting the brain, heart, abdominal wall, and limbs 4, 1
• Recognize that sensitivity of ultrasound at 11-14 weeks for detecting congenital anomalies is only about 50% compared to 75% at 18-22 weeks, so early normal findings do not provide complete reassurance 4, 2

Mandatory Second Trimester Evaluations

• Perform a comprehensive anatomic survey at 18-22 weeks regardless of fetal DNA analysis or karyotype results, as the risk of major structural anomalies remains elevated even in euploid fetuses 4, 1
• Obtain fetal echocardiography at 18-22 weeks even if karyotype is normal, as cardiac defects remain at elevated risk in euploid fetuses with history of increased NT 4, 1, 2
• The expected detection rate for major cardiac anomalies at this gestational age exceeds 80% 4

Ongoing Monitoring Through Pregnancy

• Institute serial fetal surveillance with periodic ultrasound examinations to monitor fetal growth and well-being throughout the pregnancy 4, 1
• The risk of adverse pregnancy outcomes, including intrauterine demise, increases proportionally with the degree of NT enlargement, even in the absence of chromosomal or structural abnormalities 4, 1

Risk Stratification by NT Measurement

Degree of Risk

• NT ≥3 mm: One-third will have chromosomal abnormalities 1, 2
• NT ≥3.5 mm: Risk increases exponentially with measurement; this threshold represents the >99th percentile where adverse perinatal outcome risk becomes statistically significant in euploid fetuses 5
• The adverse outcome risk increases in an exponential fashion as NT measurement increases above these thresholds 5

Special Consideration for Borderline Measurements

Even isolated NT measurements from 2.5-2.9 mm increase the risk of fetal chromosomal aneuploidy 2.5-fold compared to NT <2.5 mm (3.4% vs 1.4%), though the risk of pathogenic copy number variants is not significantly elevated 6

Critical Pitfalls to Avoid

Do Not Be Falsely Reassured

• Never assume normal karyotype or negative cell-free DNA eliminates the need for anatomic survey and fetal echocardiography—structural defect risk remains elevated in euploid fetuses 4, 1
• A normal NT does not exclude chromosomal abnormalities, as 30% of Down syndrome fetuses have normal NT measurements 3, 2
• If NT normalizes on follow-up scan after 11 weeks, do not be falsely reassured—fetuses with early increased NT that subsequently normalizes still have an 8.5% incidence of adverse outcomes 7

Timing Considerations

• NT measurement must be performed between 11+0 to 14+0 weeks of gestation, as the measurement loses predictive value outside this narrow window 3, 2
• For NT detected before 11 weeks (CRL <45 mm), invasive prenatal testing should be offered even if NT normalizes on follow-up, as adverse outcome risk remains considerable at 22-52% depending on initial NT thickness 7

Twin Gestations: Modified Approach

• In dichorionic twins, calculate fetus-specific risks using each twin's individual NT measurement 3, 2
• In monochorionic twins, use the average NT thickness of both fetuses for pregnancy-specific risk calculation 3, 2
• Standard singleton thresholds (≥3 mm) apply to twins, as NT distribution does not differ significantly between singletons and twins 3, 2
• Fetal echocardiography is indicated for any dichorionic twin with increased NT, though performing echocardiography on twins is technically challenging due to maternal and fetal factors 4

Prognostic Information for Counseling

If Midgestation Ultrasound is Normal

If the fetus survives until midgestation and a targeted ultrasound at 20-22 weeks reveals no abnormalities, the risk of adverse perinatal outcome and postnatal developmental delay is not statistically increased in euploid fetuses 5

Overall Detection Rates

NT combined with first trimester serum markers (PAPP-A and free β-hCG) detects approximately 90% of affected pregnancies with a 5% false-positive rate 3, 2