Effects of prenatal development on growth, adiposity and metabolism: The developmental origins hypothesis

Intrauterine life may be a critical period for the programming of later body composition and risk of metabolic disease. Experimental studies in animals indicate that particular maternal exposures during pregnancy can have long-term effects on offspring body composition and metabolic risk. Within the Southampton Women’s Survey, we have shown greater adiposity in the offspring in association with higher maternal adiposity, poor quality maternal diets in pregnancy (characterised by frequent consumption of energy-dense, micronutrient-poor foods), low maternal vitamin D status, excess gestational weight gain, and short duration of breastfeeding. In animals the environment during early life induces altered phenotypes in ways which are influenced or mediated by epigenetic mechanisms, but until recently there has been little direct evidence in humans. Using Sequenom MassARRAY we have found that greater methylation of a single CpG within the RXRA promoter measured in umbilical cord was strongly associated with greater adiposity in later childhood. Perinatal measurements of DNA methylation explained >25% of the variance in childhood adiposity. These findings were replicated in a second independent cohort. Our data provide the first human evidence that epigenetic processes in non-imprinted genes have an important role in later body composition. Understanding developmental influences on childhood obesity has important implications for the design of intervention studies.