The Influence of Maternal and Social Factors During Intrauterine Life

Abstract

Adult chronic disorders, such as hypertension, diabetes, osteoporosis, or obesity, represent an increasing proportion of the global burden of disease. These disorders are the result of complex interactions between genetic and environmental factors. There is increasing epidemiological and experimental evidence showing that the influence of environmental exposures takes place not only after birth but also during intrauterine life. Although randomized interventional studies are difficult to perform in this setting, a variety of data suggest that factors such as maternal nutrition and stress result in adaptive changes in the fetus, affect fetal growth and development, and influence the risk of disease in later life. The mechanisms translating environmental exposures into disease risk may be multiple and include direct effects on developing organs and, especially, epigenetic changes. Epigenetic mechanisms modify gene activity in a relatively stable manner, without changing the DNA sequence. They are powerful means to adapt to the environmental influences, but they may also favor the development of disease. DNA methylation is the most extensively studied epigenetic signature. Many animal studies and human epidemiological observations strongly suggest that the intrauterine environment influences the DNA pattern, which, in turn, determine the risk of disease during adulthood. So far, the stronger evidence is for the relationship between undernutrition while in utero and the later risk of metabolic and cardiovascular disorders. Also, some studies suggest that intrauterine growth is associated with postnatal skeletal size and bone mineral content in early postnatal years. Whether it translates into the risk of fractures at advanced age is still unclear. Overall, data accumulated during the last two decades are consistent with a role of exposures during intrauterine life in determining the risk of many complex prevalent disorders. Of course, other factors, including the genetic background and postnatal environmental factors, are also important. However, already available data call for attention to the modifiable circumstances of early life, including both prenatal period and childhood, in order to minimize the risk of disease in later life as adults.