Grant: Operating Grant

Neural tube defects (NTDs) as a group represent one of the most common serious birth defects and result from growth abnormalities of cells during very early embryo development. They are thought to result from a complex interaction between genetic and environmental influences. NTDs have been shown to be reduced, but not eliminated, through population-wide folate supplementation programs. We suggest that poor folate uptake by the placenta is a major contributor to NTDs. Low folate may lead to abnormal DNA methylation, a chemical modification to the DNA that helps regulate how genes are turned on and off in the cell. We plan to study methylation differences in the DNA of placentas and fetuses affected with NTDs. By identifying the specific changes associated with abnormal fetal development we will be better able to understand the causes and identify those chemicals in our environment that might have detrimental effects on development. Furthermore, such changes may be useful to subgroup NTDs into folate pathway dependent and independent causes and thus improve our ability to evaluate the impact of folate supplemenation on NTDs.