Second-trimester dimeric inhibin-A in Down's syndrome screening

Initial studies of immunoreactive inhibin using a commercial assay have shown levels to be increased in three second-trimester series of maternal samples from Down's syndrome-affected pregnancies. This assay detected non-specifically all forms of circulating inhibin, dimeric and free alpha subunits, whether fully or partially processed. More recently, a new specific assay for dimeric inhibin-A has shown elevated results in both a first-trimester and a second-trimester series of cases. In order to assess the value of dimeric inhibin-A as a potential marker in the second trimester, we have analysed 157 Down's syndrome cases and used 367 unaffected cases across the gestational range 14-20 weeks to establish control medians and population parameters. In our series, the median MOM in Down's cases was 1.77, significantly higher than in the controls. At a 5 per cent false-positive rate, dimeric inhibin-A alone identified 37 per cent of cases. When used in conjunction with maternal age and other marker combinations, mathematical modelling showed detection rates rising from 48 per cent (inhibin-A plus age) to 61 per cent (inhibin-A, free beta hCG, age) and 68 per cent (inhibin-A, AFP, free beta hCG, age). Our data suggest that dimeric inhibin-A may have greater potential earlier in gestation when median levels at 14-16 weeks are 1.92 compared with 1.46 at 17-23 weeks. Dimeric inhibin-A may be a valuable addition to screening protocols, particularly in early gestations.