What is the sensitivity of ultrasound findings for detecting trisomy 21 (Down syndrome) in pregnant individuals, particularly those of advanced maternal age or with a family history of genetic disorders?

Sensitivity of Ultrasound Findings for Trisomy 21

Second-trimester ultrasound soft markers detect approximately 59-82% of trisomy 21 cases when used as a screening tool, with the detection rate heavily dependent on which specific markers are present and whether multiple markers are identified. 1, 2, 3

Detection Rates by Specific Ultrasound Markers

The sensitivity of ultrasound for trisomy 21 varies substantially based on which markers are evaluated:

Individual Soft Markers (Second Trimester)

• Cardiac anomalies: Highest independent predictor with strongest association 4
• Structural malformations: 28% detection rate 2
• Nuchal fold thickening (≥6 mm): 32% detection rate, with 99.5% specificity 2, 4
• Short femur: 31% detection rate 2
• Short humerus: 33% detection rate 2
• Short ear length: 71% detection rate 2
• Echogenic bowel: 7% detection rate 2
• Echogenic intracardiac focus, choroid plexus cysts: Not independent predictors and do not significantly increase detection 4

Combined Marker Approach

When any abnormal ultrasound marker is present in second-trimester genetic sonography, the overall sensitivity reaches 80-82% for trisomy 21, with specificity of 91%. 3 However, this comes at the cost of a false-positive rate of approximately 5-9%. 3, 4

First-Trimester Ultrasound Performance

First-trimester ultrasound markers demonstrate superior performance when combined appropriately:

• Nuchal translucency (NT) alone: Part of combined first-trimester screening achieving 83-86% detection 5
• Absent nasal bone: Present in approximately 70% of trisomy 21 fetuses at 11-14 weeks 6
• Integrated first-trimester approach (NT + absent nasal bone + ductus venosus flow or tricuspid flow): Can achieve detection rates up to 97% when combined with biochemical markers 6, 7

Critical Context: Ultrasound vs. Modern Screening

The role of ultrasound soft markers has fundamentally changed with the introduction of cell-free DNA (cfDNA) screening, which achieves 98.8-99% detection rate for trisomy 21 with only 0.04% false-positive rate. 1 This represents a paradigm shift from the historical reliance on ultrasound-based risk modification. 1

Current Clinical Framework

• Isolated soft markers should not be used to modify risk in patients who have already had negative cfDNA or serum screening 1
• Ultrasound soft markers retain value primarily in patients who have not undergone aneuploidy screening 1
• Multiple soft markers or structural abnormalities substantially increase aneuploidy risk and warrant detailed evaluation regardless of prior screening 1

Important Caveats

Limitations Affecting Sensitivity

• Detection rates are indication-specific: Sensitivity ranges from 80% in women with advanced maternal age alone to 100% in women with both abnormal biochemistry and advanced maternal age 3
• Operator dependence: Requires experienced sonographers with validated, reproducible definitions for each marker 1
• Isolated pyelectasis: Not associated with increased trisomy 21 risk unless combined with other markers 2

Risk Modification

A normal second-trimester genetic ultrasound reduces the likelihood of trisomy 21 by approximately 80%, yielding a negative predictive value of 99.6%. 3 However, this should not replace diagnostic testing when clinically indicated. 1

Practical Algorithm

When an isolated soft marker is identified:

1. Perform detailed anatomic survey to confirm the finding is truly isolated (no structural anomalies, growth restriction, or additional markers) 1

2. Review prior screening results: 1

   • If cfDNA or serum screening negative: No further aneuploidy evaluation needed for most isolated markers
   • If no prior screening: Offer noninvasive testing for aneuploidy
   • If multiple markers present: Consider diagnostic testing regardless of prior screening

3. Specific high-risk markers requiring special consideration: 1, 4

   • Thickened nuchal fold (≥6 mm): Offer genetic counseling even with negative serum screening
   • Cardiac anomalies or structural malformations: Strong independent predictors warranting diagnostic testing
   • Absent/hypoplastic nasal bone: Associated with significantly increased risk

The key pitfall to avoid is using isolated soft markers to modify risk in patients who have already undergone high-quality cfDNA screening, as this approach is outdated and increases unnecessary invasive testing. 1