Genetic and Environmental Influences on Early Growth: The Generation R Study

Epidemiological studies have demonstrated an inverse relationship between birth weight and the risk of adult disease, such as type 2 diabetes (T2D) and cardiovascular disease. These fi ndings have led to the developmental origins of health and disease hypothesis or ‘DOHaD-hypothesis’. Initially, publications reporting these associations were received with some skepticism. Recently, however, these relationships have been found to be quite robust, though the eff ect size might not be as large as originally estimated. The main proposed causal pathway underlying the association between low birth weight and metabolic phenotype is a suboptimal fetal environment which leads to fetal undernutrition (Figure 1).4,5 This undernutrition subsequently causes developmental adaptations that permanently alter fetal growth, physiology and metabolism, also referred to as fetal programming.4 Though this programming might lead to an increased survival rate in early life, the developmental adaptations can have long-lasting eff ects on disease in adulthood.

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