Ultrasound markers and anomaly screening

1st Trimester Screen - Early Peeks & Peaks

• Window: 11-14 weeks gestation.
• Purpose: Early risk stratification for aneuploidies, primarily Trisomy 21 (Down syndrome) and Trisomy 18 (Edwards syndrome).
• Components (Combined Test):
  • Ultrasound: Nuchal Translucency (NT). A fluid collection >3.0 mm is a key marker.
  • Maternal Serum Analytes:
    • ↓ PAPP-A (Pregnancy-associated plasma protein-A).
    • ↑ Free β-hCG.

⭐ Absence of the fetal nasal bone on the 11-14 week ultrasound is a powerful soft marker for Trisomy 21.

2nd Trimester Quad - The Marker Squad

• Performed at 15-22 weeks gestation to screen for aneuploidy and neural tube defects (NTDs). Measures four maternal serum markers:

  • Alpha-fetoprotein (AFP)
  • Human chorionic gonadotropin (hCG)
  • Unconjugated estriol (uE3)
  • Inhibin A

• Interpretation of Results:

  • Trisomy 21 (Down Syndrome): ↓ AFP, ↓ uE3, ↑ hCG, ↑ Inhibin A
  • Trisomy 18 (Edwards Syndrome): ↓ AFP, ↓ uE3, ↓ hCG
  • NTDs or Abdominal Wall Defects: ↑ AFP

• 📌 HI-E: In Trisomy 21, HCG & Inhibin A are High; Estriol & AFP are low.

⭐ The most common cause of an elevated maternal serum AFP (MSAFP) is incorrect gestational dating. Always confirm dates with ultrasound before proceeding to further diagnostic testing.

Ultrasound Clues - Soft Markers, Hard Calls

• Soft Markers: Non-specific findings that ↑ risk of aneuploidy but are not diagnostic; many resolve spontaneously.
  • ↑ Nuchal Translucency/Fold: Strongest marker for Trisomy 21. NT >3 mm in 1st trimester.
  • Echogenic Intracardiac Focus (EIF): Bright spot on fetal heart papillary muscle.
  • Echogenic Bowel: Bowel appears as bright as bone. Assoc. w/ Trisomy 21, CF, CMV infection.
  • Mild Renal Pyelectasis: AP renal pelvic diameter >4 mm.
  • Choroid Plexus Cyst: Often transient; stronger association with Trisomy 18.

⭐ While most soft markers are non-specific, a thickened nuchal fold (≥6 mm) in the second trimester is one of the strongest individual markers for Down syndrome.

cfDNA Screening - Fetal Fragments Foretell

• Non-invasive screening test performed at or after 10 weeks gestation.
• Analyzes cell-free DNA from placental trophoblasts circulating in maternal blood.
• Primarily screens for trisomies 21, 18, 13, and sex chromosome aneuploidies.
• Represents a screening, not a diagnostic test; results require confirmation.

⭐ A low fetal fraction (<4%) can lead to a test failure or an uninformative result, requiring a redraw or alternative screening methods.

High‑Yield Points - ⚡ Biggest Takeaways

• Increased nuchal translucency (NT) is a key first-trimester marker for aneuploidies like Trisomy 21.
• An absent or hypoplastic nasal bone is another strong first-trimester indicator of Down syndrome.
• Abnormal ductus venosus Doppler and tricuspid regurgitation suggest aneuploidy or cardiac defects.
• Key second-trimester soft markers include echogenic intracardiac focus and choroid plexus cysts.
• The 18-22 week anatomy scan is crucial for detecting major structural anomalies.
• Abnormal markers prompt cfDNA or invasive testing like amniocentesis.