Developmental Origins of Health and Disease: Environmental Exposures

The developmental origins of health and disease (DOHaD) approach has evolved over the past 20 years, and the current hypothesis proposes that fetal adaptations to intrauterine and maternal conditions during development shape structure and function of organs. Here we present a review of some environmental exposures that may trigger fetal maladaptations in these processes, including three examples: exposures to tobacco smoke, antidepressant medication, and folic acid deficits in the food supply. We provide a selected review of current research on the effects of each of these exposures on fetal development and birth outcomes, and use the DOHaD approach to suggest how these exposures may alter long-term outcomes. In the interpretation of this literature, we review the evidence of gene-environment interactions based on evaluation of biological pathways and evidence that some exposures to the fetus may be moderated by maternal and fetal genotypes. Finally, we use the design of the National Children's Study (now in progress) to propose how the DOHaD approach could be used to address questions that have emerged in this area that are relevant to reproductive medicine and subsequent health outcomes.