South African Society for Ultrasound
in Obstetrics and Gynaecology


Soft markers of Down syndrome

Lou Pistorius
September 2002

Two questions for today:
  • What are soft markers?
  • How should they be used?
What are soft markers of Down syndrome?
Ultrasound Clinical finding
Soft marker Minor abnormality
Hard marker Major abnormality

i.e.: a soft marker is a sonographic finding at the anatomy scan which:
  • occurs in otherwise normal fetus in the general population,
  • occurs more commonly in fetus with Down syndrome,
  • is not the sonographic presentation of a major abnormality,
  • and increases the relative risk of Down syndrome
For example:
… examples
  • Nuchal fold more than 6 mm
  • Echogenic bowel
  • Short femur
  • Echogenic focus in the heart
  • Choroid plexus cysts
  • Mild hydronephrosis
  • and many, many more…
Where do soft markers come from?
  • Ultrasound = clinical examination of unborn infant
  • Soft markers = sonographic markers of clinical features of Down syndrome
Where do soft markers fit in?
Evolution of screening for Down syndrome

How to screen for Down syndrome: Maternal age

Maternal age: efficiency
  • 5% false positive rate,
  • 30% sensitivity
Biochemical screening:
…how does it work?
Biochemical screening:
…how does it work?
Biochemical screening:
…how does it work?

Adjusted risk = background risk x previous history x likelihood ratio

Maternal age & biochemical screening: efficiency
  • 5% false positive rate,
  • 65% sensitivity
From biochemical screening to soft markers:
  • Biochemical screening:
    • Ultrasound for gestational age (therefore 15 – 18 weeks)
    Soft markers:
    • Ultrasound as clinical examination (still 15 – 18 weeks)
Soft markers
  • 50% sensitivity
  • 10% false positive rate
How to combine risks?
  • Scoring index (Benacerraf)
  • Relative risks (Nicolaides)
  • Multivariant analysis (Bahado-Singh)
Relative risks:
  • Nuchal fold more than 6 mm 10x
  • Echogenic bowel 7x
  • Short femur 4x
  • Echogenic focus in the heart 3x
  • Choroid plexus cysts 1.5x
  • Mild hydronephrosis 1.5x
Soft markers: relative risks
  • Advantage: easy to combine with prior risk
  • Disadvantage: heuristics & biases
  • Are the markers:
    • independent
      "the more, the merrier"
  • or related
    • "making the same mistake with greater confidence"
  • Regression analysis (Bahado-Singh)
    • Guess what is left?
      • Regression analysis

      • What is left?
        • Nuchal skin fold
        • Humerus length
      • Relative risks:
        • Nuchal skin fold
        • Humerus length
      Nuchal translucency is not a soft marker
      Nuchal translucency screening
      • 5% false positive rate;
      • 75% sensitivity
      Nicolaides (n = 100 000)

      First trimester biochemistry
      • Combined with NT:
      • 5% false positive rate
      • 80% sensitivity
      Is it…
      time for a total shift to first-trimester screening for Down syndrome

      Cuckle Lancet 2001; 358:1658-9. … thereafter: ignore soft markers?
      (a good test cannot be improved by combining it with a bad test)