Clinical validation of a new dimeric inhibin-A assay suitable for second trimester Down's syndrome screening

To compare the Down's syndrome screening performance of a simplified dimeric inhibin-A assay (Diagnostic Systems Laboratories (DSL)) with an assay whose clinical utility has been established (Serotec).

A case control set consisting of 51 Down's syndrome and 245 matched unaffected pregnancies collected as part of an earlier multicentre cohort study.

Sera were assayed for dimeric inhibin-A using the DSL assay and Serotec reference assay. Data analysis included a method comparison of mass values, fit of data to a logarithmic Gausian distribution, and determination of detection and false positive rates. In addition, 234 fresh sera were assayed using the simplified method.

The two assays showed a high correlation (r = 0.93) but average concentrations of the DSL assay were 48% higher. However, the differences were basically proportional over the range of values important for screening. The detection rate was essentially equivalent for the DSL assay whether analysed univariately or in combination with other markers (for example, 79% v 75% at a 5% false positive rate for the DSL and Serotec assays for the combination of alpha fetoprotein, unconjugated oestriol, human chorionic gonadotrophin, and dimeric inhibin-A, respectively). The 234 dimeric inhibin-A values measured on fresh sera fitted a logarithm Gaussian distribution for the DSL assay, as indicated by the fit to a probability plot.

The Down's syndrome screening performance of a simplified dimeric inhibin-A immunoassay was equivalent to a more labour intensive established dimeric inhibin-A assay.