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

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  • OBJECTIVES: Document patient choices and screening performance (false positive and detection rates) when three improved Down syndrome screening protocols were introduced coincidentally. METHOD: Second-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. RESULTS: Over 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%). CONCLUSIONS: Integrated 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.


  • 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

  • 2010