The hypothesis that early-life growth patterns contribute to non-communicable diseases initially emerged from historical cohort studies, consistently associating low birth weight and infant weight gain with later disease risk. Cohort studies offer crucial life-course data on disease aetiology, but also suffer from important limitations, including the difficulty of adjusting for confounding factors and the challenge of interpreting data on early growth. Prospective randomised trials of infant diet appear to provide evidence in direct contradiction to cohort studies, associating faster early growth with disease risk. The present article attempts to resolve this contradiction on two grounds. First, insufficient attention has been directed to inconsistency of outcomes between cohort studies and prospective trials. Cohort studies can assess actual mortality, whereas prospective trials investigate proxies for disease risk. These proxies are often aspects of phenotype that reflect the 'normalisation' of metabolism in response to growth, and not all those displaying normalisation in adolescence and early adulthood may go on to develop disease. Second, a distinction is made between 'metabolic capacity', defined as organ development that occurs in early life, and 'metabolic load', which is imposed by subsequent growth. Disease risk is predicted to be greatest when there is extreme disparity between metabolic capacity and metabolic load. Whereas cohort studies link disease risk with poor metabolic capacity, prospective trials link it with increased metabolic load. Infancy is a developmental period in which nutrition can affect both metabolic capacity and metabolic load; this factor accounts for reported associations of both slow and fast infant growth with greater disease risk.
Early origins of disease hypothesis: Historical cohort studies: Conflicts in evidence:Phenotypic inductionDuring the 20th century the burden of disease in industrialised countries shifted dramatically from infectious to non-infectious diseases as a result of changes in sanitation, hygiene, living conditions and nutrition (1) . In 1880 infectious, parasitic and respiratory diseases accounted for approximately 50% of all deaths in England and Wales, whereas cancers and diseases of the circulatory system accounted for <10%. By 1990 the corresponding percentages had altered to 17 and 70 (1) . The modern killers became known as 'lifestyle' diseases, attributed to behavioural factors such as diet, sedentary behaviour and tobacco smoking, although both genetic factors and broader environmental factors such as pollution were also acknowledged to be important. Public health campaigns to reduce the prevalence of CVD and associated diseases such as type 2 diabetes, hypertension and stroke focused on dietary change (decreased consumption of fat, salt and refined carbohydrate, increased consumption of fruit, vegetables, vitamins and minerals), reductions in smoking and alcohol consumption and the promotion of leisure-time physical activity. Within the last two d...