Gene-environment interactions underlying the etiology of neural tube defects

Neural tube defects (NTDs) consist of severe structural malformations of the brain and spinal cord and are the second most common structural birth defect in humans, accounting for approximately 2700 affected pregnancies every year in the United States. These numbers are highly significant, considering that birth defects remain a leading cause of infant mortality in the United States, affecting approximately 120,000 babies born annually. Survivors of these congenital malformations face long-term disability and lifelong challenges imposed by severe physical burdens compromising the afflicted individual's overall quality of life. Clearly, birth defects, and especially NTDs remain a global public health challenge, and the source of significant financial repercussions for healthcare systems worldwide. In order to better understand the role gene-environment interactions play in the etiology of NTDs, this chapter provides an overview of NTD phenotypes and their embryonic origins, discusses the genetic landscape of NTDs as it is currently understood, with a focus on experimental models that best illustrate how environmental factors modulate individual susceptibility to these birth defects. As folic acid interventions have proven to be effective in reducing the prevalence of NTDs, the chapter ends with a discussion on the impact that maternal dietary status has on NTD prevalence from a population perspective.