TY - JOUR

T1 - ADAM12: a novel first-trimester maternal serum marker for Down syndrome.

AU - Laigaard, Jennie

AU - Sørensen, Tina

AU - Fröhlich, Camilla

AU - Pedersen, Bent Nørgaard

AU - Christiansen, Michael

AU - Schiøtt, Kirsten

AU - Uldbjerg, Niels

AU - Albrechtsen, Reidar

AU - Clausen, Helle V

AU - Ottesen, Bent

AU - Wewer, Ulla M

N1 - Keywords: ADAM Proteins; Adult; Biological Markers; Case-Control Studies; Chorionic Gonadotropin, beta Subunit, Human; Disintegrins; Down Syndrome; Enzyme-Linked Immunosorbent Assay; Female; Humans; Maternal Age; Membrane Proteins; Metalloendopeptidases; Predictive Value of Tests; Pregnancy; Pregnancy Trimester, First; Pregnancy Trimester, Second; Pregnancy-Associated Plasma Protein-A; Prenatal Diagnosis

PY - 2003

Y1 - 2003

N2 - OBJECTIVES: 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. CONCLUSION: ADAM12 is a promising marker for Down syndrome.

AB - OBJECTIVES: 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. CONCLUSION: ADAM12 is a promising marker for Down syndrome.

U2 - 10.1002/pd.762

DO - 10.1002/pd.762

M3 - Journal article

C2 - 14691998

VL - 23

SP - 1086

EP - 1091

JO - Prenatal Diagnosis

JF - Prenatal Diagnosis

SN - 0197-3851

IS - 13

ER -