The prenatal period is a crucial period of brain development, and therefore the maternal environment can have an impact on fetal neurodevelopment. In particular, proteins of the maternal immune system during pregnancy may be able to affect the development of the fetal brain, as these proteins can cross the placenta and enter fetal tissues. Preliminary results have provided evidence that elevated levels of certain immune system proteins in the blood of pregnant women may be associated with an increased risk of autism in their children. During mid-pregnancy, these researchers found elevated levels of specific cytokines (proteins which attract immune cells to sites of infection), and the presence of autoantibodies, proteins which can recognize and bind to cells and proteins in the fetus. Maternal cytokines and autoantiodies could affect fetal brain development by binding and signaling to cells and proteins in the fetal brain, or they could affect the immune system of the fetus. These researchers will extend their preliminary data by conducting a large controlled study on the association between levels of autoantibodies and cytokines in maternal blood samples during mid-pregnancy with the associated risks of autism and mental retardation in the offspring. 1200 mother-child pairs will be included in this study, as well as 200 siblings of autistic and mentally retarded children. These data will determine whether inappropriate activation of the immune system during pregnancy is associated with an increased risk of neurodevelopmental problems. The results from this study should contribute to our understanding of the impact of the maternal environment on fetal development, and its contribution to autism. It may also provide new, early tests for an increased risk of autism.