[Second trimester screening for trisomy 21 using ADAM12-S as a maternal serum marker]

To investigate the value of a disintegrin and metalloproteinase 12 secreting form (ADAM12-S) as a maternal serum marker in second trimester screening for trisomy 21 (Down syndrome, DS), and to develop an appropriate prenatal DS screening protocol.

Serum samples were collected from 53 pregnant women carrying a trisomy 21 fetus and 621 pregnant women with matched gestational age and weight carrying a healthy fetus. ADAM12-S concentrations were determined with a time-resolved fluorescence immunoassay (TRFIA). Curve fitting by weighted regression and other statistical methods were conducted, and the model was optimized for prenatal trisomy 21 screening program in second trimester. ADAM12-S alone or in combination with other two- or three-combination test was selected as a serum marker for prenatal second-trimester screening of trisomy 21 by calculation of detection rate (DR) and false positive rate (FPR).

By comparison, the median multiple of the median (MoM) value of ADAM12-S in DS pregnancy group was higher than that of the control group (P< 0.01). When FPR = 5%, the DR of ADAM12-S was 28.3%, and the positive and negative likelihood ratios were 5.66 and 0.75, respectively. The DR of three-combination test of ADAM12-S, alpha-fetoprotein (AFP) and free beta subunit of human chorionic gonadotropin (β-HCG) has increased to 52.80% from 39.62% of the conventional two-combination test (AFP and free β-HCG). For women with a risk between 1/300 and 1/1000 by two-combination test for DS, the DR has increased from 39.62% to 47.12%, but FPR only increased by 0.8% after adding ADAM12-S as a maternal serum marker.

Considering the increased DR of pregnancies with a risk between 1/300 and 1/1000 in second trimester, ADAM12-S may provide a feasible maternal serum maker when combined with AFP and free β-HCG. The cost-effectiveness ratio is reasonable.