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28: Combining first and second trimester Down syndrome screening results: A simple, effective approximation

      Objective

      The proper interpretation of a second trimester serum Quad test in a woman who has had a first trimester Combined test is to calculate risk from maternal age and all seven marker levels. However, software needed for risk calculation is not always available and a simple approximation is the composite likelihood ratio (CLR), defined as (first trimester Combined risk ÷ maternal age risk) * Quad risk. We assessed the discriminatory power of this approach.

      Study design

      Data collected from women in the FASTER trial were analyzed to calculate Down syndrome (DS) risk from ultrasound nuchal translucency measurement and maternal serum markers in the first and second trimester. 32,269 women carrying singleton pregnancies completed both first and second trimester screens; 86 women had Down syndrome fetuses. DS detection and false-positive rates (FPRs) for the CLR were compared against first trimester Combined (NT, free β-hCG and PAPP-A), second trimester Quad (AFP, hCG, uE3, and inhibin), and Integrated (first trimester NT and PAPP-A, and second trimester Quad) tests.

      Results

      DS detection rates and FPRs with a 1 in 270 second trimester risk cut-off, and detection rates for a fixed 5% FPR are shown in the Table. CLR outperformed first trimester Combined, Quad, and Integrated tests. Properly calculating risk from all seven marker levels detected 92% of DS cases at a 4.9% FPR, and a detection rate of 92% (79/86) for a 5% FPR.
      Tabled 1Performance of CLR compared with other methods
      First CombinedQuadIntegratedCLR
      Sensitivity85% (73/86)84% (72/86)88% (76/86)92% (79/86)
      FPR6.7%9.3%4.9%5.3%
      Sensitivity for 5% FPR85% (73/86)81% (70/86)88% (76/86)91% (78/86)

      Conclusion

      The CLR is an effective method of interpreting screening results, despite only calculating DS risk approximately. The CLR may be useful when first and second trimester screens are performed in different laboratories or a provider does not have access to software to perform the Integrated screen.