ADAM12: a novel first-trimester maternal serum marker for Down syndrome.
OBJECTIVE
The concentration of bioavailable insulin-like growth factor (IGF) I and II is important to foetal growth. It is regulated by insulin-like growth factor binding proteins (IGFBP) 1 through 6. Proteolytic cleavage of IGFBP-3 takes place in human pregnancy serum; accordingly, IGFBP-3 serum levels decrease markedly during pregnancy. ADAM12 (A disintegrin and metalloprotease) is an IGFBP-3 and IGFBP-5 protease and is present in human pregnancy serum. The goal of this study was to determine whether ADAM12 concentration in maternal serum is a useful indicator of foetal health.


METHODS
We developed an enzyme-linked immunosorbent assay (ELISA) for the quantification of ADAM12 in serum. The assay range was 42 to 667 micro g/L. Recombinant ADAM12 was used as the standard for calibration.


RESULTS
We found that ADAM12 was highly stable in serum. Serum concentration increased from 180 micro g/L at week 8 of pregnancy to 670 micro g/L at 16 weeks, and reached 12 000 micro g/L at term. In 18 first-trimester Down syndrome pregnancies, the concentration of ADAM12 was decreased, thus the median multiple of mean (MoM) value was 0.14 (0.01-0.76). A detection rate for foetal Down syndrome of 82% for a screen-positive rate of 3.2% and a 1:400 risk cut-off was found by Monte Carlo estimation using ADAM12 and maternal age as screening markers.


CONCLUSIONS
ADAM12 is a promising marker for Down syndrome.
Laigaard
Jennie
J
Department of Gynecology and Obstetrics, Rigshospitalet, University of Copenhagen, Denmark.
Sørensen
Tina
T
Fröhlich
Camilla
C
Pedersen
Bent Nørgaard
BN
Christiansen
Michael
M
Schiøtt
Kirsten
K
Uldbjerg
Niels
N
Albrechtsen
Reidar
R
Clausen
Helle V
HV
Ottesen
Bent
B
Wewer
Ulla M
UM
D051722:ADAM Proteins; D000072199:ADAM12 Protein; D000328:Adult; D015415:Biomarkers; D016022:Case-Control Studies; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000097:blood; D019483:Disintegrins / Q000097:blood*; D004314:Down Syndrome / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008423:Maternal Age; D008565:Membrane Proteins / Q000097:blood*; D008666:Metalloendopeptidases / Q000097:blood*; D011237:Predictive Value of Tests; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011262:Pregnancy Trimester, Second; D011266:Pregnancy-Associated Plasma Protein-A / Q000378:metabolism; D011296:Prenatal Diagnosis
D015415:Biomarkers; D018997:Chorionic Gonadotropin, beta Subunit, Human; D019483:Disintegrins; D008565:Membrane Proteins; D051722:ADAM Proteins; D000072199:ADAM12 Protein; C000606480:ADAM12 protein, human; D008666:Metalloendopeptidases; D011266:Pregnancy-Associated Plasma Protein-A