We know that events in early life such as being born small or premature can increase the risk of developing diabetes, high blood pressure, heart disease and stroke in later life. The mechanisms through which these adverse early life events increase the risk of these diseases is not clear. To address this in a previous study we have used a technique to look at the activity of all the genes at once (this is known as gene expression profiling). We compared two groups of children:
1. Those born small but with good growth in early childhood (high risk cardiovascular disease) and
2. Children born small with poor growth in childhood (low risk cardiovascular disease). We were able to identify changes in pathways related to insulin (involved in diabetes) and the renin-angiotensin system (involved in blood pressure). This study involved only 33 children. We will examine how levels of activity these pathways vary in healthy children and in those exposed to adverse early life factors (obesity, prematurity, being born small) and how the levels of pathways activity relate to blood pressure, blood fats and blood sugar levels.

The proposed study seeks to extend these preliminary data. By using the ALSPAC gene expression profiles we will be able to examine the activity of the genes in the pathways we previously identified in a much larger group of children (approximately 1000).

We will be able to examine the effects of several different early life events on these pathways - prematurity, being born small (with or without good postnatal growth) and obesity. We will also examine how, in a group of normal healthy children, changes in activity levels of these pathways affect measures of health such as blood pressure, cholesterol and blood sugar levels.