ACCUMULATION OF RISK

One of the earliest descriptions of accumulation of risk was Riley’s concept of insult accumulation,⁴⁰ the notion that life course exposures or insults gradually accumulate through episodes of illness and injury, adverse environmental conditions, and health damaging behaviours. One of the purposes of life course epidemiology is to test the extent of cumulative damage to biological systems as the number, duration or severity of exposures increase, and as body systems age and become less able to repair damage. The accumulation of different types of exposures (such as environmental, socioeconomic, and behavioural) may cause long term damage⁴¹ with exposure risk being either independent (fig 1, model (a)) or clustered (fig 1, model (b)). The latter is known as an accumulation model with risk clustering.¹⁶ Life course epidemiology shares with social epidemiology a particular interest in exposures that cluster because they are often related to an individual’s or family’s socioeconomic position in society.

• Download figure
• Open in new tab
• Download powerpoint

Figure 1

Life course causal models.

BIRTH COHORT EFFECTS

Birth cohort refers to the location of an individual in historical time as indexed by their year of birth. An environmental change (such as an improvement or deterioration of living standards) that affects the health of children may show up several decades later as birth cohort differences in adult mortality.⁴² Cohort differences in adult disease can also occur if there are cohort variations in risk factors such as childbearing characteristics or the adoption of habits such as smoking⁴³ that have long term effects on health. Birth cohorts may also be differentially affected by rapid or extensive social change.⁴⁴ The impact of such change, creating possibilities for turning points on life trajectories with short and long term effects on health, often varies by age.² The changing size of birth cohorts (such as the post-war “baby boom” generation) is itself one of the forces for social change. Age-cohort models identify possible cohort effects. More complex age-period-cohort models can be fitted to help distinguish these effects but require assumptions in order to estimate the parameters of the model because of the linear dependency among the three factors.^45,46 Cohort effects are easiest to distinguish when disease trends have accelerated, decelerated, or changed direction. Where they are steady and linear they cannot be reliably distinguished from period effects.⁴³

CHAINS OF RISK MODEL

A chain of risk model refers to a sequence of linked exposures that raise disease risk because one bad experience or exposure tends to lead to another and then another. Different types of chains can confer increased or decreased risk. Our definition of chains of risk (or protective chains) is based on the idea of “chain reactions” put forward by Rutter⁴⁷ to explain continuities between early experiences and adult psychosocial function. It also resembles what has been described as a “pathways model”.^13,48 Social, biological, and psychological chains of risk are possible and involve “mediating factors” and often “modifying factors”. The sequential links are probabilistic rather than deterministic. It is possible to conceive of two different types of chains of risk. One model is that each exposure not only increases the risk of the subsequent exposure but also has an independent effect on disease risk irrespective of the later exposure (fig 1, model c). When each adverse experience increases the risk of disease in a cumulative fashion this is called an “additive effect” and may be a special case of an accumulation model. Alternatively, earlier exposures have no effect on disease risk without the final link in the chain that precipitates disease onset (fig 1, model (d)). Such a “trigger effect” describes the situation when it is only the final link in the chain that has a marked effect on disease risk.

CONTEXT

Context refers to the location of an individual by time and place. Place refers to both geographical location and to group membership in terms of family, friends or age, and on the basis of class, ethnicity, residence, and gender that arise out of the social and economic structure of society. Context may affect exposure to risk and the individual’s response strategies. Application of a life course perspective to contextual as well as individual effects on health implies understanding the effects of changing contexts over time on the life course of individuals.

CRITICAL PERIOD

In the natural sciences a critical period of development refers to a time window when intrinsic changes in the organisation of living systems or sub-systems towards increasing complexity, greater adaptivity and more efficient functioning occurs rapidly and may be most easily modified in a favourable or unfavourable direction.⁴⁹ In life course epidemiology the relevance of changes during a critical period is in respect of their long term effects on disease risk many years later. Thus, we define a critical period as a limited time window in which an exposure can have adverse or protective effects on development and subsequent disease outcome. Outside this developmental window there is no excess disease risk associated with exposure.

CRITICAL PERIOD MODEL

A critical period model of disease causation is when an exposure acting during a critical period of development has effects on the structure or function of organs, tissues or body systems that are not modified in any dramatic way by later experience, and that precipitate disease later in life. Also known as “biological programming” or as a “latency model”,¹³ it underlies the fetal origins of adult disease hypothesis. An expanded version of the basic critical period model includes the possibility that the effect of an exposure during a critical period of development on later disease risk may be dramatically changed by later physiological or psychological stressors. The critical period with later effect modifiers implies investigating plausible interactive effects between early and later life risk factors.

EMBODIMENT

Embodiment is a term common to both social epidemiology²¹ and life course epidemiology. It describes how extrinsic factors experienced at different life stages are inscribed into an individual’s body functions or structures. This may be through developmental processes associated with critical periods, habituation, learning, damage, and repair. The term “biological embedding”^48,50 has a similar meaning although it tends to be applied to neurobiological or psychobiological mediators of the early social environment on child development and life course health.

INDUCTION AND LATENCY PERIODS

While different definitions of these terms appear in the epidemiological literature, we favour those used by Rothman.⁵¹Induction period is defined as the time between exposure and initiation of the disease process, hence it is a characteristic of a relation between a specific exposure and a specific disease. Life course epidemiologists have a particular interest in causal relations with long induction periods. Latency period refers to the period between disease initiation and detection, and is a characteristic of the disease (onset of symptoms) or the healthcare system (diagnosing the disease). If an exposure has a long induction and/or latent period, its public health importance may vary according to when in the life course one is exposed. Variations in the time between induction and latency periods make it difficult to detect the true causal agents, and the strength of association between an exposure and disease can be diluted or missed if the wrong time frame is measured. Often it is difficult to observe the time of disease initiation and this prevents researchers from distinguishing empirically between the induction and latent periods. Latency period should not be confused with latency model, which is an alternative term for a critical period model.

LIFE CYCLE/LIFE SPAN/LIFE COURSE

The concept of a life cycle has generally been used in other scientific disciplines to describe a series of distinct, bounded life stages which are socially or biologically determined.⁵² In contrast the concept of the life span used in psychology assumes that development and aging form a continuous process from birth to death. The distinction between life span and life course, the term used more commonly in sociology, is mainly a matter of scientific history.

MEDIATING FACTOR

A risk or protective factor mediates the association between exposure and disease when it chronologically follows the exposure and is conceptualised as lying, at least partly, on the causal pathway. Life course epidemiology requires an explicit temporal theoretical model that distinguishes between mediating factors (post-exposure of interest) and confounding factors (conceptualised as prior to and/or tangential to understanding the effects of the exposure of interest).

MODIFYING FACTOR

A risk or protective factor modifies the association between an exposure and disease when the causal effect of the exposure of interest differs across levels of the modifying factor. Investigation of modifying factors provides information about the nature of the causal process. Effect modification is known as interaction—“synergism” if the modifying variable enhances the effect of the explanatory variable or “antagonism” if it diminishes it. Interactions are thought to be common features of life course processes and should be investigated where plausible biological, behavioural or social hypotheses exist. Well defined theoretical life course models are needed to interpret the biological or social significance of observed interactions. Empirical assessment of interaction is the source of much debate in epidemiology and needs to be carefully considered in terms of additive or multiplicative risk models.^51,53

PLASTICITY

Plasticity is the potential for change in intrinsic characteristics in response to environmental stimuli. It is measured by within person variability. Like life course perspectives in other disciplines,⁵⁴ the search for the range of plasticity and age associated changes and constraints is a fundamental quest of life course epidemiology.

RESILIENCE

Resilience is a dynamic process of positive adaptation in the face of adversity.⁵⁵ The focus of research has been on the intrinsic and extrinsic factors associated with educational, emotional and behavioural resilience of children.^55,56 There has been less focus on health outcomes and on long term outcomes in general.⁵⁷ A question that has hardly been addressed is whether resilience in development, and its associated factors, have long term health benefits or costs. For example, the fetal origins hypothesis assumes that adaptations for survival made by the fetus in response to adversity (maternal undernutrition) raise the risk of chronic disease risk in later life.¹⁸ Life course epidemiology has contributions to make to an integrated science of human adaptation and development⁵⁶ that also includes an aging perspective. Both share a focus on lifelong biological, psychological, and social processes and their interrelationships.

SENSITIVE PERIOD

Like critical periods, sensitive periods are also times of rapid individual change but there is more scope to modify or even reverse those changes outside the time window. Thus a sensitive period in life course epidemiology is a time period when an exposure has a stronger effect on development and subsequent disease risk than it would at other times. Outside the time period any excess risk will be weaker.

SUSCEPTIBILITY

Within epidemiology susceptibility has been defined in terms of Rothman’s “causal pie model”,⁵¹ which describes susceptibility as “a term that refers to the condition of having one of two interacting causes already and therefore being susceptible to the effect of the other.” (page 172). It is usually used where host factors increase the likelihood that another exposure will produce disease. Host factors refer to both intrinsic factors as well as prior exposures that have become embodied over time. Thus susceptibility is a process occurring over time that may eventually lead to disease via the completion of the last piece of the causal pie. This idea has been given greater salience with the emergence of genetic epidemiology and the growing attention to gene-environment interactions.⁵⁸ In the wider scientific literature susceptibility is often used synonomously with vulnerability and conveys a broadly similar process.

TIME

Time is a fundamental concept in life course epidemiology, both in terms of life time (as indexed by the chronological age of individuals) and historical time at the population level (as indexed by membership of a birth cohort). Changing individuals must be studied in a changing environment (see context). The effect of an exposure on a health outcome may be dependent on the duration or timing of exposure. Critical and sensitive periods are so defined because the age of the individual at the time of exposure is assumed to affect the long term outcome. In other words, they represent qualitatively different exposure-time interactions. For critical periods there is no excess risk associated with exposure outside this time window whereas for sensitive periods it is merely weaker. This is similar to Elder’s “life stage principle”.² Similarly, social roles and life events have different social meanings and possibly differential health effects depending on their timing and whether they are typical for a person’s age, gender, or culture.

TRAJECTORY, TRANSITION AND TURNING POINTS (ADAPTED FROM ELDER²)

A trajectory provides a long term view of one dimension of an individual’s life over time. These may be social states (such as work, marriage, socioeconomic position), psychological states (such as depression) or physiological states (such as lung function). Implicit is the idea of a normative trajectory around which individuals deviate. Transitions are short-term and embedded in trajectories, marking a change in social, psychological, or physiological states. A marked change of direction is referred to as a turning point.

VULNERABILITY

Vulnerability is the opposite of resilience and refers to a dynamic process of negative adaptation in the face of adversity. The negative physiological or behavioural response is shaped by prior embodiment of extrinsic factors as well as intrinsic characteristics.

CONCLUSION

Life course epidemiology has blossomed in the past five years as a natural response to the limitations of previous aetiological models of chronic disease. We have welcomed the opportunity here and elsewhere¹⁶ to clarify its purpose and guiding principles as misunderstandings have inevitably arisen. A life course perspective in epidemiology has been erroneously limited to notions of risk accumulation,^59,60 or associated only with psychosocial theories of social epidemiology.²¹ Rather we would argue that it represents an attempted synthesis of previous models of disease causation (such as adult lifestyle, biological programming, and social causation) that is scientifically interesting, conceptually and methodologically challenging, inherently interdisciplinary and policy relevant. A life course approach has been adopted in all but name by researchers whose focus was initially restricted to fetal and infant life but who have now extended their frame of reference to include postnatal growth and development.^59,61 Childhood indicators of adult disease risk include childhood stature, particularly leg length,⁶² relative weight,⁶³ energy intake and IQ.^64,64a There is also more willingness among those who focus on adult risk factors to recognise the importance of early life factors.⁶⁵ In epidemiology there is a growing appreciation of the need for a temporal perspective for conventional so called “adult” risk factors.^66–68 Age at onset, duration and changes in levels of exposure to conventional risk factors may alter their effects on adult disease risk and impact on long term disease trends.⁶⁹

What are the future challenges for life course epidemiology? One challenge is the continued development of testable theoretical models that elucidate the risk and protective factors at each life stage, and the underlying biological, psychological, and social pathways that link these together across one or more generations. The life course models defined in this glossary are not mutually exclusive and may operate simultaneously. It may not be easy to distinguish these models empirically²⁴ nor to develop standardised and acceptable methods of combining cumulative exposures.³⁶ These are just two of a number of complex methodological problems facing life course epidemiology. The second challenge is the ability of life course epidemiology to help explain temporal, geographical, and social patterns of disease distribution. Thirdly, changing individuals need to be studied in a changing world and we would like to see a life course approach fully integrated into the study of broadly defined contextual health effects. Fourthly, the growing genetic knowledge and development of cheap and reliable methods to analyse DNA on large population samples, has opened up possibilities for studying the interactive effects of genetic and environmental factors across the life course. Lastly, and most important of all, there is the need to translate our new knowledge into interventions and policy recommendations designed to improve the long term health of individuals, social groups, and societies.^14,70–72