Amniotic fluid levels of dimeric inhibins, pro-alpha C inhibin, activin A and follistatin in Down's syndrome

OBJECTIVE In the second trimester of pregnancy, inhibin A is significantly increased in maternal serum and decreased in amniotic fluid in Down's syndr ome pregnancies compared to normal. We wished to further evaluate the level s of inhibin A, inhibin B, pro-alpha C inhibin, activin A and the binding p rotein follistatin in amniotic fluid in Down's syndrome and control pregnan cies, DESIGN Case-matched control study, PATIENTS 29 Down's syndrome and 290 chromosomally normal control pregnancie s were identified from records and amniotic fluid, collected at second trim ester amniocentesis, retrieved from routine storage for analysis. MEASUREMENTS Inhibin A, inhibin B, pro-alpha C inhibin, total activin A and follistatin were measured using sensitive and specific enzyme linked immun osorbent assays, RESULTS The median (10th-90th percentiles) amniotic fluid inhibin A level i n the control pregnancies increased from 334 (122-553) ng/l at 14 weeks' to 695 (316-1475) ng/l at 10 weeks' gestation. The corresponding figures for inhibin B and the alpha-subunit precursor inhibin pro-alpha C were 632 (185 -1354) and 2062 (1237-3381) ng/l, respectively at 14 weeks' and 2439 (748-5 307) and 3115 (2021-6567)ng/l, respectively at 19 weeks' gestation, Total a ctivin A increased from 3795 (1554-5296) at 14 weeks' to 5086 (3059-8224) a t 18 weeks' gestation, Expressed as multiples of the median (MoM) the media n (95% CI) amniotic fluid levels of inhibin A, inhibin B, pro-alpha C inhib in and acitivin A in the Down's syndrome samples were 0.77 (0.59-0.85), 0.9 4 (0.63-1.23), 0.77 (0.49-0.84) and 0.77 (0.53-0.87), respectively. Compare d to controls the levels of inhibin A, pro-alpha C inhibin and activin A we re significantly lower in Down's syndrome pregnancies (P<0.01, Mann-Whitney U test), Follistatin levels in the controls declined slightly from 2106 (1 421-3538) ng/l at 14 weeks' to 1600 (1281-2543)ng/l at 18 weeks' gestation. Levels in the Downs' syndrome pregnancies were similar to controls. CONCLUSIONS The data suggest that the production, secretion or metabolism o f the inhibin alpha- and beta(A)-subunits is altered in Down's syndrome pre gnancies in the second trimester.