Life-long echoes--a critical analysis of the developmental origins of adult disease model.

The hypothesis that there is a developmental component to subsequent adult disease initially arose from epidemiological findings relating birth size to either indices of disease risk or actual disease prevalence in later life. While components of the epidemiological analyses have been challenged, there is strong evidence that developmental factors contribute to the later risk of metabolic disease--including insulin resistance, obesity, and heart disease--as well as have a broader impact on osteoporosis, depression and schizophrenia. We suggest that disease risk is greater when there is a mismatch between the early developmental environment (i.e., the phase of developmental plasticity) versus that experienced in mature life (i.e., adulthood), and that nutritional influences are particularly important. It is also critical to distinguish between those factors acting during the developmental phase that disrupt development from those influences that are less extreme and act through regulated processes of epigenetic change. A model of the relationship between the developmental and mature environment is proposed and suggests interventional strategies that will vary in different population settings.