Dimeric inhibin A as a marker for Down's syndrome in early pregnancy

Background. In screening for Down's syndrome in the second trimester of pregnancy, the concentrations of alpha-fetoprotein, the β subunit of human chorionic gonadotropin, and intact human chorionic gonadotropin in maternal serum are widely used markers. We investigated a new marker, dimeric inhibin A, and compared its predictive value with that of the established markers. Methods. Serum samples were obtained at 7 to 18 weeks of gestation from 58 women whose fetuses were known to be affected by Down's syndrome, 32 whose fetuses were affected by trisomy 18, and 438 whose fetuses were normal, and the samples were analyzed for each marker. Individual serum concentrations of each marker were converted to multiples of the median value at the appropriate length of gestation in the women with normal pregnancies, and rates of detection of Down's syndrome by screening for inhibin A in various combinations with the other markers were estimated by multivariate analysis. Results. In the women with fetuses affected by Down's syndrome, the serum inhibin A concentrations were 2.06 times the median value in the women with normal pregnancies (P<0.001). This compared with 2.00 times the median for the β subunit of human chorionic gonadotropin, 1.82 times the median for intact human chorionic gonadotropin, and 0.72 times the median for alpha- fetoprotein. The serum concentrations of inhibin A in the women with fetuses affected by Down's syndrome did not appear to be significantly elevated above normal until the end of the first trimester and were not significantly different from normal in the women with fetuses affected by trisomy 18 (P=0.17). The rate of detection of Down's syndrome was 53 percent and the false positive rate was 5 percent when alpha-fetoprotein, the β subunit of human chorionic gonadotropin, and maternal age were used together as predictors. The detection rate increased to 75 percent when inhibin A was added (P=0.002). Conclusions. In the second trimester of pregnancy, measuring inhibin A in maternal serum, in combination with measurements of alpha- fetoprotein and the β subunit of human chorionic gonadotropin, significantly improved the rate of detection of Down's syndrome.