Second and first trimester estimation of risk for Down syndrome: implementation and performance in the SAFER study Journal Articles uri icon

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  • AbstractObjectivesDocument patient choices and screening performance (false positive and detection rates) when three improved Down syndrome screening protocols were introduced coincidentally.MethodSecond‐trimester ‘triple marker’ screening was expanded by adding second‐trimester dimeric inhibin‐A (four‐marker), with or without first‐trimester pregnancy‐associated plasma protein‐A (five‐marker). Nuchal translucency (NT) measurements were included when available from accredited sonographers (six‐marker). For assigning risk, two sets of marker distribution parameters were evaluated.ResultsOver 3.5 years, 8571 women enrolled (median age 30.6 years). Uptake of the four‐, five‐ and six‐marker protocols was 18%, 46% and 36%, respectively. Of those selecting an integrated test (five or six markers), 9.7% did not provide the second trimester serum sample. False positive rates decreased with added markers (5.2%, 5.1% and 2.5%, respectively) and varied between the two parameter sets, while detection remained high. Overall, 21 of 23 cases were detected (91%, 95% CI 73–98%) at a 4.2% false positive rate (95% CI 3.3–5.1%).ConclusionsIntegrated screening protocols were chosen 4.6 times more often than four‐marker screening (82% vs. 18% uptake). Overall detection was higher and false positives lower, consistent with recent guidelines. Important performance factors include gestational dating method, risk cut‐off, and the parameter set used to assign risk. Copyright © 2010 John Wiley & Sons, Ltd.


  • MacRae, Andrew R
  • Chodirker, Bernie N
  • Davies, Gregory A
  • Palomaki, Glenn E
  • Knight, George J
  • Minett, Jane
  • Kavsak, Peter
  • Toi, Ants
  • Chitayat, David
  • Van Caeseele, Paul G

publication date

  • May 2010