Hypotheses on the fetal origins of adult diseases: Contributions of epidemiological studies

Epidemiological studies have demonstrated associations between low birth weight and cardiovascular disease, type 2 diabetes and their risk factors in adult life. These findings have led to sharp debates in the literature concerning potential methodological study flaws and the effect size and causality of the associations. More recent studies seem to have overcome most methodological flaws and suggest a small effect size of low birth weight on adult diseases for the individual. However, the effect size may still be important on a population level. Various causal pathways have been hypothesized as mechanisms underlying these associations. These hypotheses have proposed central roles for (1) fetal undernutrition, (2) increased cortisol exposure, (3) genetic susceptibility and (4) accelerated post-natal growth. These hypotheses have been studied in various epidemiological study designs. Thus far, it is still not known which mechanisms underlie the associations between low birth weight and diseases in adult life. The causal pathways linking low birth weight to diseases in later life seem to be complex and may include combined environmental and genetic mechanisms in various periods of life. Well-designed epidemiological studies are necessary to estimate the population effect size and to identify the underlying mechanisms. This knowledge is needed to develop strategies for identifying groups at risk and prevention focused on early life.