Lecture 18 - Life course epidemiology

What is the aim of life course epidemiology?

Aim to integrate and extend the 3 main theories of disease aetiology

• Foetal/developmental origins of adult disease 

• Adult lifestyle  

• Social causation theories 

The initial focus of life course epidemiology was what?

Initial focus: early life factors -> clinical disease end-points 

1980s:

• Primary focus on ‘conventional’ adult lifestyle models of chronic disease since 1950s but growing dissatisfaction with them 

  • Poor predictors of individual risk 

Why is life course epidemiology relevant to new policies?

• Evidence for the life course approach is strong 

  • What happens in early life affects health and wellbeing later in life 

• Successful policies in response to an ageing population are likely those which take a whole life course approach  

Why is time important in a life course approach?

Encourages consideration of different exposures in the context of:

• Timing

• Duration

• Temporal ordering

Aims to provide aetiological insights into lifelong processes which influence ageing and health

Also gathers evidence on the type, timing and targeting of the most effective interventions to promote health

How is a theoretical life course framework constructed?

More than just the collection of exposure data across life 

• Requires diagrammatical ordering of variables across life with temporal ordering of exposure variables and their inter-relationships explicitly shown 

• Used for hypothesis generation and testing, enables researchers to outline a priori not only hypothesised associations of factors earlier in life with later outcomes but also possible underlying social and biological pathways 

How is a theoretical life course framework turned into testable hypothesis?

Need to breakdown theoretical frameworks into smaller testable parts 

• Modelling the whole life course pathway would be too complicated 

Life course models were originally used to test the influence of the timing and duration of exposure across life on later disease risk 

• Critical and sensitive period models 

• Accumulation of risk models 

Models are not mutually exclusive and may operate simultaneously  

What is a critical period model? Give an example.

The only time period during which an exposure (A) has an effect 

• E.g. thalidomide in utero and limb abnormalities  

What is a sensitive period model? Give an example.

A time period during which an exposure (B) has a greater effect than outside this period 

• E.g. smoking before 1^st pregnancy and breast cancer risk 

What do accumulation of risk models aim to model?

Exposures or insults gradually accumulate across life through episodes of illness and injury 

• Accumulation of risk models aim to model this

What is ‘Accumulation of independent risks’?

Accumulation of exposure to different, uncorrelated risk factors (A, B and C) causes long term damage and increases disease risk 

What is an example of ‘accumulation of independent risks’?

• Being burgled

• Death of child

• Job loss

All increase risk of depression

What is ‘Accumulation of clustered risks’?

Accumulation of exposures to different risk factors (A, B and C) which are clustered as each are associated with another risk factor (D) which causes long term damage and increases disease risk 

What is an example of ‘accumulation of clustered risks’?

Low childhood socioeconomic position

• Passive smoke

• Physical inactivity

• Poor diet

All increase risk of adverse health behaviour in adulthood

What are the two types of ‘chain of risk’ models?

• Additive effect models

• Trigger effect models

What are ‘Additive effect’ models?

Type of ‘Chain of risk’ model.

• Each exposure (A,B) not only increase the risk of subsequent exposure (B,C) but also has an independent effect on disease risk (irrespective of later exposure)

What is an example of ‘additive effects’?

Smoking

• Poor lung function

  • Sedentary behaviour

All increase risk of cardiovascular disease

What are ‘Trigger effect’ models?

Type of ‘Chain of risk’ model.

• Earlier exposures (A and B) influence the risk of subsequent exposures but have no effect on disease risk without the final exposure (C) 

What is an example of ‘trigger effect’?

• Low childhood socioeconomic position

  • Overcrowding in home

    • H pylori infection

      • Peptic ulcer development

What are the limitations of life course models?

• Focus on lifetime exposures rather than the responses 

• Not all outcomes are ‘hard’ disease end-points 

• Original examples consider exposures at different time points when quite often we’re investigating exposure to the same risk factor over time 

• Don’t accurately represent the complex and dynamic interplay of developmental, risk factor and age-related trajectories across life 

What is the ideal study which could be used to test a life course hypothesis?

Assessment of outcomes 

• At different life stages 

• Baseline measures ascertained prior to onset of major age-related decline  

• With repeat measures over time 

Data on potential risk factors 

• From birth (or earlier) onwards 

• With repeat measurements over time (to facilitate study of different life course models) 

• That are potentially modifiable  

Which types of studies are used for life course research?

• National and regional birth cohorts

• Historical cohorts

• Adult cohorts with retrospective data on childhood

• Natural experiments

• Long-term follow-up of randomized controlled trials (RCTs)

What are national and regional birth cohorts?

National and regional birth cohorts 

• Data collected prospectively across life from birth 

What are historical cohorts?

Historical cohorts

• Some data ascertained earlier in life and study participants then retraced later in life 

What are adult cohorts with retrospective data on childhood?

Adult cohorts with retrospective data on childhood

• Repeat measures in adulthood and recalled data on childhood 

What are the benefits of using multiple ‘life course’ studies?

• No one study has data on all measures of interest at all relevant life stages 

• Facilitates study of cohort differences  

  • Are associations generalizable or cohort specific 

• May impact on associations observed and relative public health importance of different risk factors 

• Important differences in environment across time

  and between countries

How has life course epidemiology impacted understanding of factors across life relating to chronic pain later in life?

• Serious illness before 25 has been associated with increased risk of chronic widespread pain at age 68y 

What associations were found during studies of childhood factors and back pain?

Persistent back-pain 

• Taller childhood height (in women), abdominal pain in adolescence, poor care in childhood, poorer maternal health 

Back-pain in early adulthood only

• Taller childhood height (in women) 

Mid-adulthood onset of back-pain

• Abdominal pain in adolescence