The present inventors describe ADAM12 as an important indicator of foetal and placental development, function and changes in the level of ADAM12 may reflect the presence, classification or progression of disease. The present invention provides a method, an assay and a kit for providing an indication of Down Syndrome. The present application demonstrates that ADAM12 is reduced in first trimester and increased in second trimester Down Syndrome pregnancies. ADAM12 may thus serve as a maternal serum risk marker for fetal disease. It is thus an object of the present invention to provide an improvement of the existing marker tests that exhibits a decreased false positive rate or improved detection rate of chromosomal disease or adverse pregnancy outcome.