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 syndrome pregnancies compared to normal. We wished to further evaluate the levels of inhibin A, inhibin B, pro-alpha C inhibin, activin A and the binding protein follistatin in amniotic fluid in Down's syndrome and control pregnancies.


METHODS
Case-matched control study.


METHODS
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.


METHODS
Inhibin A, inhibin B, pro-alpha C 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 alpha-subunit precursor inhibin pro-alpha C 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-alpha C 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-alpha C 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 alpha- and beta A-subunits is altered in Down's syndrome pregnancies in the second trimester.
Wallace
E M
EM
Department of Obstetrics and Gynaecology, Monash University, Clayton, Victoria, Australia. Euan.Wallace@med.monash.edu.au
D'Antona
D
D
Shearing
C
C
Evans
L W
LW
Thirunavukarasu
P
P
Ashby
J P
JP
Shade
M
M
Groome
N P
NP
D028341:Activins; D000653:Amniotic Fluid / Q000737:chemistry*; D016022:Case-Control Studies; D004314:Down Syndrome / Q000175:diagnosis*; D005260:Female; D005315:Fetal Diseases / Q000175:diagnosis*; D038681:Follistatin; D006023:Glycoproteins / Q000032:analysis; D006801:Humans; D007265:Inhibins / Q000032:analysis; D010455:Peptides / Q000032:analysis; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D011296:Prenatal Diagnosis; D029584:Prostatic Secretory Proteins; D011498:Protein Precursors / Q000032:analysis; D018709:Statistics, Nonparametric
D038681:Follistatin; D006023:Glycoproteins; D010455:Peptides; D029584:Prostatic Secretory Proteins; D011498:Protein Precursors; C043076:beta-microseminoprotein; C094377:inhibin-alpha subunit; C095971:inhibin-alpha subunit precursor; D028341:Activins; D007265:Inhibins