The Concept of Phenotypic Induction (‘Programming’) and Implications for Growth

Abstract

Growth patterns in early life have been strongly associated with the risk of diseases such as stroke, hypertension, type 2 diabetes, obesity and cardiovascular disease in adulthood. This has focused attention on the long-term consequences of developmental plasticity during early life periods of sensitivity. Epidemiological studies have consistently associated both (a) low birth weight and (b) increased childhood weight gain, obesity, rich diet and physical inactivity with risk of degenerative metabolic diseases. This chapter presents a model focusing on the development of ‘metabolic capacity’ during the growth periods of fetal life and early infancy and the development of ‘metabolic load’ during subsequent growth periods. Metabolic capacity emerges during early ‘critical windows’ and refers to traits such as nephron number, pancreatic B-cell mass and other components of organ structure and function. Metabolic load emerges primarily from early childhood onwards and is characterised by traits such as tissue masses, dietary glycaemic load and metabolic inflexibility. Using this model, a high ratio of metabolic load to metabolic capacity increases the risk of degenerative diseases by inducing alterations in blood pressure, insulin metabolism and lipid metabolism. Moderate normalisation of metabolic load is possible with few ill effects, but high metabolic load (e.g. from obesity) exacerbates the deleterious consequences and induces disease. An increased metabolic load during early infancy also appears to have long-term deleterious effects. However, the long-term consequences of infant growth rate appear to vary between populations, and public health policies for developing countries should not be based on studies conducted in industrialised populations. This model of the phenotypic induction of metabolism highlights the notion that adult disease risk is the product of ‘disordered growth’ between different growth periods. No single period of growth is critical in the induction of disease risk; rather, a number of scenarios are possible, in each of which metabolic load interacts with metabolic capacity to determine disease risk. The key implications for paediatricians are that growth rates have long-term as well as short-term health consequences, and the optimal growth pattern is likely to reflect a trade-off between costs and benefits in different periods of the life course. Public health policies must also take into account the fact that metabolic profile emerges throughout the life cycle and reflects trans-generational influences.