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Background In screening for Down's syndrome in the second trimester of pregnancy, the concentrations of alpha-fetoprotein, the
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
Conclusions In the second trimester of pregnancy, measuring inhibin A in maternal serum, in combination with measurements of alpha-fetoprotein and the
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. 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 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). subunit of human chorionic gonadotropin, significantly improved the rate of detection of Down's syndrome.
Source Information
From the Duncan Guthrie Institute of Medical Genetics, Glasgow (D.A.A., J.A.C., Y.P., M.M., J.M.C.); the University of Edinburgh Department of Obstetrics and Gynaecology, Centre for Reproductive Biology, Edinburgh (E.M.W.); the Medical Research Council Reproductive Biology Unit, Centre for Reproductive Biology, Edinburgh (I.A.S.) — all in Scotland; the School of Biological and Molecular Sciences, Oxford Brookes University, Oxford, England (N.P.G.); and NTD Laboratories, Huntington Station, New York (J.N.M.).
Address reprint requests to Dr. Aitken at the Duncan Guthrie Institute of Medical Genetics, Yorkhill, Glasgow G3 8SJ, United Kingdom.
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