What are the common soft markers on prenatal ultrasound and how should they be evaluated and managed?

Soft Markers on Prenatal Ultrasound: Evaluation and Management

Definition and Common Soft Markers

Soft markers are minor ultrasound findings in the second trimester that usually do not represent structural abnormalities but are associated with increased aneuploidy risk, though their clinical significance has evolved substantially with modern screening methods. 1

The most commonly identified soft markers include: 1

• Echogenic intracardiac focus (EIF)
• Choroid plexus cysts (CPCs)
• Echogenic bowel
• Single umbilical artery (SUA)
• Urinary tract dilation (UTD)
• Shortened humerus or femur
• Thickened nuchal fold
• Absent or hypoplastic nasal bone
• Mild ventriculomegaly 2, 3

Initial Approach When a Soft Marker is Identified

When any soft marker is detected, perform a detailed obstetrical ultrasound examination (CPT 76811) to confirm the finding is truly isolated—meaning no structural abnormalities, growth restriction, or additional soft markers are present. 1

Critical First Steps:

• Verify the marker is isolated through comprehensive anatomic survey 1
• Review prior aneuploidy screening results (serum screening or cfDNA) 1
• Document the discussion and patient decision in the medical record 1
• Use shared decision-making incorporating patient preferences and resource availability 1

Risk Stratification Based on Marker Type and Number

Single Isolated Soft Markers:

The clinical significance of isolated soft markers has diminished substantially in the era of cfDNA screening, as most confer only small-to-moderate increases in aneuploidy risk. 1

Likelihood ratio categories: 1

• LR 1.5-5: Small increase (most isolated soft markers fall here)
• LR 5-10: Moderate increase
• LR >10: Substantial increase

Echogenic intracardiac focus (EIF) is the most common soft marker (accounting for >90% in some series) but has the lowest predictive value for aneuploidy with a positive predictive value of only 20% even when detected. 4

Multiple Soft Markers or Structural Abnormalities:

The presence of multiple soft markers or any structural abnormality substantially increases aneuploidy risk and requires individualized evaluation with strong consideration for diagnostic testing regardless of prior screening results. 1, 5

When 3 soft markers are present with an outflow tract heart defect, diagnostic testing (amniocentesis or CVS) is recommended rather than screening alone, as this combination confers a substantial likelihood of Down syndrome. 5

Management Algorithm Based on Prior Screening Status

Scenario 1: Patient Had Low-Risk cfDNA or Serum Screening

For most isolated soft markers in patients with low-risk cfDNA screening:

• Reassurance is appropriate as cfDNA has >99% detection rate for trisomies 21,18, and 13 1
• No additional aneuploidy testing is typically needed for isolated EIF, CPC, or mild pyelectasis 1
• Consider marker-specific follow-up (see below) 1

Important exceptions requiring further evaluation despite low-risk screening: 5, 4

• Absent or hypoplastic nasal bone (PPV 100% in one series) 4
• Echogenic bowel (PPV 50%, also associated with cystic fibrosis and CMV) 4
• Multiple soft markers (PPV 100% in one series) 4
• Any structural cardiac abnormality 5

Scenario 2: Patient Had No Prior Aneuploidy Screening

Offer aneuploidy screening (preferably cfDNA) or diagnostic testing when an isolated soft marker is identified in unscreened patients. 1

For high-risk markers (absent/hypoplastic nasal bone, echogenic bowel, multiple markers), proceed directly to genetic counseling and offer diagnostic testing. 5, 4

Scenario 3: Multiple Soft Markers or Structural Abnormalities Present

Offer diagnostic testing (amniocentesis or CVS) rather than screening, as only diagnostic testing completely removes residual aneuploidy risk. 5, 6

Arrange fetal echocardiogram if cardiac involvement is suspected. 5

Provide genetic counseling to discuss implications and management options. 5

Marker-Specific Follow-Up Recommendations

Echogenic Bowel:

• Offer diagnostic testing for aneuploidy 1, 7
• Test for cystic fibrosis (carrier screening if not done) 1
• Test for congenital CMV infection 1
• Third-trimester ultrasound for growth assessment 1
• Weekly antenatal surveillance starting at 36 weeks 1

Urinary Tract Dilation:

• Grade A1: Ultrasound at 32 weeks to determine need for postnatal urology/nephrology follow-up 1
• Grade A2-3: Individualized follow-up ultrasound with planned postnatal follow-up 1

Shortened Humerus or Femur:

• Third-trimester ultrasound for reassessment and growth evaluation 1
• Note: Shortened femur is associated with preterm delivery, low birth weight, and small-for-gestational-age infants 8

Echogenic Intracardiac Focus (EIF):

• No additional follow-up needed if isolated and low-risk screening 1
• Most common marker but least clinically significant 4

Choroid Plexus Cysts (CPCs):

• No additional follow-up needed if isolated and low-risk screening 1
• Historically associated with trisomy 18 but very low positive predictive value 3, 7

Mild Ventriculomegaly:

• Associated with trisomy 21 2, 3
• Also associated with non-chromosomal abnormalities including intraventricular hemorrhage 2
• Requires detailed evaluation for associated brain pathology 2

Critical Pitfalls to Avoid

Do not rely solely on screening tests (serum or cfDNA) when multiple soft markers or structural abnormalities are present—diagnostic testing is indicated. 5

Do not use singleton screening cutoffs or algorithms for twin pregnancies—specialized calculations are required. 6

Do not fail to perform detailed cardiac evaluation when soft markers are identified, as cardiac defects are among the strongest indicators of Down syndrome. 5

Do not underestimate the significance of absent/hypoplastic nasal bone, echogenic bowel, or multiple markers—these warrant further evaluation even with negative screening. 4

Do not equate the presence of a soft marker with definitive aneuploidy—most isolated soft markers in low-risk screened patients represent normal variants. 1, 3

Recognize that echogenic bowel has associations beyond aneuploidy (cystic fibrosis, CMV infection) that require separate evaluation. 1

Contemporary Context

The role of soft markers has fundamentally changed with widespread cfDNA screening availability—they should no longer be used as primary aneuploidy screening tools but rather as indicators for when additional evaluation beyond standard screening may be warranted. 1

In the current era, soft markers detected in patients with low-risk cfDNA results generally require only marker-specific follow-up rather than additional aneuploidy testing, with specific exceptions noted above. 1, 4