ADAM 12 may be used to reduce the false positive rate of first trimester combined screening for Down syndrome

TY - JOUR

T1 - ADAM 12 may be used to reduce the false positive rate of first trimester combined screening for Down syndrome

AU - Christiansen, Michael

AU - Pihl, Kasper

AU - Hedley, Paula L.

AU - Gjerris, Anne-Cathrine

AU - Lind, Pia Ø

AU - Larsen, Severin Olesen

AU - Krebs, Lone

AU - Larsen, Torben

N1 - (c) 2009 John Wiley & Sons, Ltd.

PY - 2010/2

Y1 - 2010/2

N2 - Background: ADAM12 has been shown to be an efficient maternal serum marker for Down syndrome (DS) in the first trimester; but recent studies, using a second generation assay, have not confirmed these findings. We examined the efficiency of a second generation assay for ADAM12. Materials and Methods: ADAM12 concentrations were determined in 28 first trimester DS and 503 control pregnancies using a novel Research DelfiaR ADAM12 kit. Log10MoM distributions of ADAM12 and correlations with other markers were established. Population performance of screening was estimated by Monte Carlo simulation. Results: ADAM12 was significantly reduced in the first trimester in DS pregnancies with a log10MoM of -0.1621 (equivalent to 0.68 MoM) (p < 0.001). The reduction decreased with advancing gestational age. ADAM12 used with PAPP-A+hCGβ+NT (CUB screening) increased the detection rate (DR) from 86% to 89% for a false positive rate (FPR) of 5%. When used for a fixed DR of 90%, the addition of ADAM12 resulted in a 25% reduction of the FPR. Conclusion: ADAM12 is a moderately effective DS marker. It is not a cost-effective addition to CUB screening, but may be used to reduce the FPR in selected high-risk cases.

AB - Background: ADAM12 has been shown to be an efficient maternal serum marker for Down syndrome (DS) in the first trimester; but recent studies, using a second generation assay, have not confirmed these findings. We examined the efficiency of a second generation assay for ADAM12. Materials and Methods: ADAM12 concentrations were determined in 28 first trimester DS and 503 control pregnancies using a novel Research DelfiaR ADAM12 kit. Log10MoM distributions of ADAM12 and correlations with other markers were established. Population performance of screening was estimated by Monte Carlo simulation. Results: ADAM12 was significantly reduced in the first trimester in DS pregnancies with a log10MoM of -0.1621 (equivalent to 0.68 MoM) (p < 0.001). The reduction decreased with advancing gestational age. ADAM12 used with PAPP-A+hCGβ+NT (CUB screening) increased the detection rate (DR) from 86% to 89% for a false positive rate (FPR) of 5%. When used for a fixed DR of 90%, the addition of ADAM12 resulted in a 25% reduction of the FPR. Conclusion: ADAM12 is a moderately effective DS marker. It is not a cost-effective addition to CUB screening, but may be used to reduce the FPR in selected high-risk cases.

KW - ADAM Proteins

KW - ADAM12 Protein

KW - Adult

KW - Biomarkers

KW - Case-Control Studies

KW - Down Syndrome

KW - False Positive Reactions

KW - Female

KW - Humans

KW - Mass Screening

KW - Membrane Proteins

KW - Pregnancy

KW - Pregnancy Trimester, First

KW - Prenatal Care

KW - Comparative Study

KW - Journal Article

U2 - 10.1002/pd.2405

DO - 10.1002/pd.2405

M3 - Journal article

C2 - 20013872

SN - 0197-3851

VL - 30

SP - 110

EP - 114

JO - Prenatal Diagnosis

JF - Prenatal Diagnosis

IS - 2

ER -