In the second trimester of pregnancy, inhibin A is significantly increased in maternal serum and decreased in amniotic fluid in Down's syndrome pregnancies compared to normal. We wished to further evaluate the levels of inhibin A, inhibin B, pro-αC inhibin, activin A and the binding protein follistatin in amniotic fluid in Down's syndrome and control pregnancies.DESIGN
Case-matched control study.PATIENTS
29 Down's syndrome and 290 chromosomally normal control pregnancies were identified from records and amniotic fluid, collected at second trimester amniocentesis, retrieved from routine storage for analysis.MEASUREMENTS
Inhibin A, inhibin B, pro-αC inhibin, total activin A and follistatin were measured using sensitive and specific enzyme linked immunosorbent assays.RESULTS
The median (10th-90th percentiles) amniotic fluid inhibin A level in the control pregnancies increased from 334 (122-553) ng/l at 14 weeks' to 695 (316-1475) ng/l at 19 weeks' gestation. The corresponding figures for inhibin B and the α-subunit precursor inhibin pro-αC were 632 (185-1354) and 2062 (1237-3381) ng/l, respectively at 14 weeks' and 2439 (748-5307) and 3115 (2021-6567) ng/l, respectively at 19 weeks' gestation. Total activin A increased from 3795 (1554-5296) at 14 weeks' to 5086 (3059-8224) at 18 weeks' gestation. Expressed as multiples of the median (MoM) the median (95% CI) amniotic fluid levels of inhibin A, inhibin B, pro-αC inhibin and acitivin A in the Down's syndrome samples were 0.77 (0.59-0.85), 0.94 (0.63-1.23), 0.77 (0.49-0.84) and 0.77 (0.53-0.87), respectively. Compared to controls the levels of inhibin A, pro-αC inhibin and activin A were significantly lower in Down's syndrome pregnancies (P<0.01, Mann-Whitney U test). Follistatin levels in the controls declined slightly from 2106 (1421-3538) 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 of the inhibin α- and βA-subunits is altered in Down's syndrome pregnancies in the second trimester.