OBJECTIVE: The objective of this study was to investigate the potential value of ADAM12 (A disintegrin and metalloprotease) in first-trimester screening for trisomy 21 and other major chromosomal abnormalities. STUDY DESIGN: The concentration of ADAM12 was measured at 11-13 weeks in cases of trisomy 21 (n = 49), trisomy 18 (n = 28), trisomy 13 (n = 20), Turner syndrome (n = 29), triploidy (n = 10), and euploid pregnancies (n = 272). The levels of ADAM12, expressed as multiples of median (MoM), were compared in cases and controls and were assessed for association with free beta-human chorionic gonadotropin (hCG) and pregnancy-associated plasma protein A (PAPP-A). RESULTS: The median ADAM12 value in trisomy 21 (0.961 MoM) was not significantly different from the euploid fetuses (1.013 MoM), but in trisomy 18 (0.697 MoM), trisomy 13 (0.577 MoM), triploidy ( 0.426 MoM), and Turner syndrome (0.747 MoM), the levels were significantly lower. In both the euploid and aneuploid pregnancies, there was a significant association between ADAM12 and free beta-hCG and PAPP-A. CONCLUSION: Maternal serum ADAM12 concentration at 11-13 weeks of gestation is unlikely to be useful in first-trimester screening for chromosomal abnormalities because in trisomy 21 the levels are not significantly different from normal, and in the other chromosomal defects, there is a significant association between ADAM12 and the traditional biochemical markers of free beta-hCG and PAPP-A.