Aim: In this prospective monocenter study, the authors aimed to investigate the correlations between levels of serum human disintegrin and metalloproteinase domain-containing protein 12 (ADAM12), pregnancy-associated plasma protein A (PAPP-A), serum-free beta hCG (fβ-hCG), and baby birth weights in two groups of pregnant women whose risks for trisomy 21 was found higher and lower than threshold value in first trimester screening test. Materials and Methods: Seventy-nine pregnant women were included the study. Using first trimester screening test, 40 of them were categorized as having above threshold risk (1/250) for trisomy 21 and, 39 of them were below threshold risk. ELISA method was used to measure the levels of serum ADAM12 and chemiluminescence method was used to measure the levels of PAPP-A and fβ-hCG. Results: In pregnant women at risk, ADAM12, PAPP-A multiple of median (MoM), and baby birth weights were found significantly lower than control group (p < 0.001, p < 0.001, and p = 0.029, respectively) while the levels of fβ-hCG MoM were higher than those of control group (p < 0.001). In the group of pregnant women having low birth weight (LBW) babies, ADAM12 levels were found lower than the group having normal birth weight babies (NBW) (p < 0.033). Also, the values of fβ- hCG MoM were found higher in comparison to NBW group (p < 0.029). A positive significant correlation was observed between ADAM12 concentrations and PAPP-A MoM (r = 0.630). Conclusions: Maternal serum ADAM12 levels are useful as biomarkers which support other screening parameters for predicting trisomy 21 risk. Additionally, maternal serum ADAM12 levels could be used for prediction of baby birth weights.