along the life course

All the world's a stage
And all the men and women merely players
They have their exits and their entrances
And one man in his time plays many parts
His acts being seven ages

As you like it, William Shakespeare


Life course epidemiology explores the exposure to risks experienced by individuals throughout their life. At different stages of life there are risks (for example during gestation, childhood, adolescence, and as adults) and these increase the likelihood of illness, particularly chronic diseases, in adult life1. In other words, it explores the extent to which there is evidence that the experiences of a child influence the health of the adult. Over the last couple of decades, this strand of epidemiology has found increasing evidence showing a strong link between early life experiences and adult health.

This article will review the current theories about life course epidemiology, explore in more detail the evidence for diabetes and coronary heart disease, and discuss the implications of this field of research for the practice of public health in the NHS.


Adult chronic diseases, or long term conditions, such as heart disease, diabetes, respiratory disease and cancer are the commonest health problems faced by the people of Scotland, and indeed most of the rest of the industrialised world. In Scotland, cancer and coronary heart disease alone account for almost half of all deaths2. In response to these health problems, research has highlighted the importance of behavioural factors such as quitting smoking, taking sufficient exercise and eating a healthy diet to reduce our risk of chronic diseases. Effective interventions designed to help us form one part of the answer.

In contrast, a life course approach suggests that the risk of developing illness is influenced by factors throughout an individual's life, starting very early in fetal development, and continuing through childhood and into adulthood. Such a model implies that adult lifestyle can only be one component that contributes to disease risk. The extent of the contribution of lifestyle in adulthood to disease risk is the subject of debate3. This life course approach implies that to understand the factors that influence the health of the population, or an individual's risk of diseases such as heart disease, we need to examine the life experiences of individuals.


Though the tree grows ever so high
The falling leaves return to the root

Malay proverb

There are two main theories in which life course epidemiologists propose that life events may influence health.

1. Fetal programming

This theory, sometimes called the 'Barker' hypothesis, or 'fetal origins' hypothesis, suggests that adult risk factors for disease are biologically programmed during critical periods of fetal growth and development. Compatible with this hypothesis, research has found that markers of prenatal nutrition, such as birth weight and placental weight: birth weight ratio, are inversely associated with adult risk of coronary heart disease, stroke and diabetes. How this would operate in relation to diabetes is discussed in detail in box 1.

2. Cumulative risk

This theory proposes that adult chronic disease risk reflects the accumulation of exposures to risk factors throughout childhood and into adult life4. These exposures may be independent, or interact, in their impact on adult risk of disease. For example, there is evidence that childhood socioeconomic position is an additional risk for cardiovascular disease, even once other risk factors, including adult socioeconomic position, are taken into account.5


Studies that compare adult onset of type 2 diabetes mellitus find an inverse relationship with birth weight. In European populations, the relationship is simple, the lower the birth weight, the higher the increased risk of glucose intolerance, gestational diabetes and type 2 diabetes mellitus in adults6. This relationship holds even when other known risk factors for diabetes, such as obesity, are taken into account. The same relationship was found in the US Nurses Health Study, which compared adult diabetes with self-reported birth weight in a cohort of over 69,000 nurses7.

Whilst the underlying mechanism for this association is not known, genetic factors, such as gene mutations in the insulin gene could explain some cases of reduced growth in the womb, low birth weight and adult onset type 2 diabetes mellitus. However, twin studies suggest that genetics cannot fully explain the association. Other theories suggest that in-utero malnutrition leads to either impaired insulin secretion or resistance to insulin8.


The relationship between low birth weight and increased adult risk of disease seen with diabetes has also been described for coronary heart disease. The risk of adult coronory heart disease is highest with children who are born small but then show rapid increase in weight during early childhood ('catch up growth')9.

Similarly, studies find an increased risk of coronory heart disease in heavier adults who had low birth weights, but not in those who remained relatively slim. This finding suggests a mechanism that is programmed in the womb but is then subject to environmental modification during adult life.

Other studies' findings are compatible with this theory that the risk of adult coronory heart disease is influenced in childhood both by prenatal factors and childhood environmental factors. For example a beneficial association has been found between breastfeeding in infancy, or low salt diet in the first six months of life, and a reduced risk of high blood pressure. The association between breastfeeding and risk of coronory heart disease is less clear.

The consensus view is that pre-adult exposures clearly have a role in the development of coronory heart disease; but these associations cannot merely be explained by confounding the adult risk factors10. One explanation is that there is a clustering of risk through exposures such as birth weight, breastfeeding and childhood growth, along with adult risk factors such as smoking, obesity and exercise.

Much may be made of a Scotchman, if he be caught young

Samuel Johnson


Of course, for public health, the important question is not whether we can use research to demonstrate an association between childhood exposures to risk factors and adult onset of chronic disease, but whether we can identify effective interventions to prevent, or mitigate, the risk of illness. For example, can we intervene to improve fetal and infant growth?

The true meaning of life is to plant trees under whose shade you do not expect to sit

Nelson Henderson

Increasing fetal growth

Factors which influence fetal growth, and which are amenable to intervention, include maternal nutrition, maternal smoking and perhaps the risk of developing pre-eclampsia, the development of maternal high-blood pressure, fluid retention and fetal growth retardation. It is also associated with pathophysiological events during placental development. The use of low dose aspirin in women at risk of developing pre-eclampsia has been associated with an 8% reduction in small-for-gestational age babies11. A maternal weight gain of <7kg is associated with a doubling of the risk of growth restriction in the fetus.

Intervention studies have found that the provision of energy supplements can lead to increases in mean birth weight (average 25g) and a reduction in the number of small for gestational age babies.

Evidence for the effect of smoking on fetal growth is even stronger. There is a clear dose-response effect, with a reduction in birth weight, on average, of 11g per cigarette/day. Intensive smoking cessation interventions have been associated with mean increases in birth weight of 28g. Increasing average birth weight is likely to have a modest impact on coronory heart disease risk. For example, Canadian data suggests that an average increase in birth weight of 100g could reduce coronory heart disease by about 2%12.


There is now a convincing body of evidence showing that exposures throughout life influence an adult's risk of developing chronic diseases, such as diabetes and coronory heart disease. To date the majority of this research has concentrated on fetal growth. While evidence is gathering on how to improve health in early years, there is little evidence that interventions to improve fetal growth will have significant impact on adult chronic disease rates. Perhaps the future will bring more convincing evidence of effective interventions.

In the meantime, our efforts to increase birthweight should be focused on reducing levels of pre-term birth and narrowing the range of weights at which children are born so that more are an optimal weight.

Action to reduce maternal and fetal exposure to the risks associated with smoking, alcohol, poor nutrition and material and social deprivation should be the foundation for improving health across the life course.


1. A life course approach to chronic disease epidemiology. First Edition, 1997, Editors: D Kuh, Y Ben-Shlomo. Oxford University Press

2. The Registrar Generalís annual report of demographic trends: Scotlandís population 2005. General Register Office for Scotland, July 2006

3. The real contribution of the major risk factors to the coronary epidemics. Magnus p, Beaglehole R, Rodgers A, Bennett S. Arch Int Med 2001;161:2657-60

4. Life course epidemiology: a glossary. D Kuh, Y Ben-Shlomo, J Lynch, J Hallqvist, C Power. J Epidemiol. Community Health 2003; 57: 778-783

5. A life course approach to chronic disease epidemiology. Second Edition, 2004, Editors: D Kuh, Y Ben-Shlomo. Oxford University Press

6. Is birth weight related to later glucose and insulin metabolism? A systematic review. CA Newsome, AW Shiell, CH Fall, DI Phillips, R Shier, CM Law. Diabet Med 2003: 20; 339-348

7. Birth weight and the risk for type 2 diabetes mellitus in adult women. JW Rich-Edwards, GA Colditz, MJ Stampfer, WC Willet, MW Gillman, CH Hennekens. Ant Intern Med 1999; 130: 278-84

8. A life course approach to diabetes. N Forouhu, E Hall, P McKeigue. Chapter 7: A life course approach to chronic disease epidemiology. Second Edition, 2004, Editors: D Kuh, Y Ben- Shlomo. Oxford University Press

9. Editorial The fetal origins hypothesis Ė 10 years on. JG Eriksson. BMJ 2005;330:1096-1097

10. Pre-adult influences on cardiovascular disease. DA Lawlor, Y Ben-Shlomo, DA Leon. Chapter 3. A life course approach to chronic disease epidemiology. Second Edition, 2004, Editors: D Kuh, Y Ben-Shlomo. Oxford University Press

11. Antiplatelet agents for preventing and treating pre-eclampsia. Knight M, Duley L, Henderson-Smart DJ, King JF. Cochrane Database of Systematic Reviews 2000, Issue 2

12. Should we intervene to improve fetal and infant growth? KS Joseph, MS Kramer. Chapter 17: A life course approach to chronic disease epidemiology. Second Edition, 2004, Editors: D Kuh, Y Ben-Shlomo. Oxford University Press