20-Week Fetus: CP Cyst + UTD A1 + Echogenic Intracardiac Focus (EIF) - Left Ventricle

Understanding Each Marker

1. Choroid Plexus Cyst (CPC)

• Fluid-filled structures within the choroid of the lateral ventricles; seen in ~1-2% of fetuses at 16-24 weeks
• Trisomy 18 association: 30-35% of trisomy 18 fetuses have CPCs; conversely, ~3% of fetuses with a CPC have trisomy 18
• Likelihood ratio (LR) for trisomy 18 when isolated: 1.5
• Size, laterality (bilateral/unilateral), and persistence do NOT alter the risk
• No association with trisomy 21
• Most CPCs resolve spontaneously by 28 weeks
• (Creasy & Resnik's MFM, p. 657)

2. Urinary Tract Dilation (UTD) A1

• The UTD classification system grades renal pelvis dilation:
  • A1 (antenatal grade 1) = mild, anterior-posterior renal pelvis diameter (APRPD) of 4-6 mm at <28 weeks
  • This is the mildest category and is considered a low-risk finding
• As an isolated soft marker, the LR for trisomy 21 is approximately 1.5-1.9
• UTD A1 isolated = low-risk for structural renal pathology; most resolve without intervention

3. Echogenic Intracardiac Focus (EIF) - Left Ventricle

• Seen in up to 5% of normal pregnancies; represents microcalcification of papillary muscle or chordae tendineae
• Trisomy 21 association: seen in 13-18% of Down syndrome pregnancies
• LR for Down syndrome when isolated: 1.8-2.8 (lower in Asian populations where it is more common in unaffected pregnancies)
• The LR does not vary by which ventricle is affected (left vs. right) or if bilateral
• (Creasy & Resnik's MFM, p. 655)
• Structurally a variation of normal; no association with cardiac structural disease

Why This Combination Matters: Multiple Soft Markers

Multiple soft markers multiplicatively increase aneuploidy risk beyond what any single marker implies.

Management Algorithm (SMFM Consult #57, 2021 - PMID 34171388)

• Isolated EIF alone: No further evaluation needed (normal variant, no echo, no follow-up US required) - GRADE 1B
• Isolated CPC alone: No further genetic testing needed - GRADE 1B
• Isolated UTD A1 alone: No further aneuploidy evaluation

• CPC alone: Counsel about trisomy 18 risk; offer cfDNA or quad screen - GRADE 1C
• EIF alone: Counsel about trisomy 21 risk; offer cfDNA or quad screen - GRADE 1B
• Multiple markers without prior screening: Strong recommendation to offer cfDNA (cell-free DNA / NIPT) or, if cfDNA unavailable, quad screen; discuss amniocentesis given multiple markers

• Offer genetic counseling and diagnostic testing (chorionic villus sampling or amniocentesis)

Practical Recommended Steps

1. Review prior screening: Was first-trimester combined screening (NT + PAPP-A + hCG) or cfDNA done? If negative, recalculate risk using background risk x combined LRs.
2. cfDNA (NIPT): Offer if not already done - provides high sensitivity for trisomy 18 and 21. At 20 weeks, cfDNA fetal fraction is typically adequate.
3. Detailed anatomy scan / Level II ultrasound: Scrutinize carefully for:
   • Trisomy 18 features: growth restriction, clenched hands/overlapping fingers, rocker-bottom feet, VSD, esophageal atresia, choroid plexus cysts (present), neural tube defects
   • Trisomy 21 features: nuchal fold thickening (>6 mm), shortened femur/humerus, echogenic bowel, absent nasal bone, AV canal defect
4. Genetic counseling: Discuss the multiplicative risk, the distinction between screening and diagnostic tests, and patient values/preferences regarding amniocentesis.
5. Amniocentesis: Discuss as an option - the only way to achieve a definitive diagnosis, particularly important given the combination of markers pointing in two different chromosomal directions (T18 for CPC, T21 for EIF + UTD).
6. UTD follow-up: Regardless of chromosomal outcome, UTD A1 warrants postnatal follow-up renal ultrasound at ~4-6 weeks of life to confirm resolution or direct urologic evaluation.

Key Points Summary

• None of these three findings alone is high-risk, but their co-occurrence moves the pregnancy out of the "isolated marker" low-risk category
• CPC primarily signals trisomy 18 risk; EIF and UTD signal trisomy 21 risk - the combination creates a dual concern
• Most important immediate action: determine prior screening status and offer cfDNA or amniocentesis
• If a prior cfDNA was already negative for T18 and T21, residual risk is low and reassurance is appropriate with detailed anatomy scan review
• EIF as an isolated finding after negative screening is a normal variant requiring no follow-up; in this context with multiple markers it cannot be dismissed