Second-trimester Down's syndrome serum screening: double, triple or quadruple marker testing?

Background: The recommendations of the UK National Screening Committee (NSC) are based on the findings of the Serum, Urine and Ultrasound Screening Study (SURUSS). Our study sought to establish if the SURUSS findings, in terms of detection rates (DR) and false-positive rates (FPR) for various second-trimester marker combinations, could be replicated in a local setting.

Methods: We investigated the effects of adding inhibin-A and unconjugated oestriol to our existing double test protocol. This retrospective study examined 1000 control pregnancies and 128 affected pregnancies.

Results: The inhibin-A method was associated with considerable assay drift and very marked within-batch imprecision (intrabatch percent coefficient of variation [CV] = 17%). At a cut-off of 1 in 250, the quadruple test showed a DR of 72%, the triple test 70% and the double test 63%. There were no significant differences between the FPRs for any of the combinations, which were all between 6.6% and 7.0% for a 1 in 250 cut-off.

Conclusions: In our view, the current inhibin-A assay is unacceptable as a screening marker due to poor assay performance. We have reviewed the NSC benchmark programme outcomes, and would suggest that the 2005 target of a DR of at least 60% with an FPR of less than 5% is achievable using triple testing in the second trimester in conjunction with universal scan dating. Our results suggest that the April 2007 target of a DR of 75% with an FPR of less than 3% is unachievable using current second-trimester maternal serum screening.