THE DEVELOPMENTAL ORIGINS OF ADULT HEALTH AND WELL-BEING
Medical Research Council-Institute of Child Health, London, UK
1. THE CONCEPT OF PROGRAMMING
Previously, nutritional scientists focused on meeting nutritional needs and preventing deficiencies. This focus has changed radically. Current interest lies in the biological effects that nutrition has on health, notably lifetime health.
That nutrition has lifetime effects raises a broader concept concerning the general importance of early life events. In this context, I popularised the term “programming” - the idea that “a stimulus or insult during a critical or sensitive period of development, can have long-term or life- time effects on the organism”. Many short-lived internal ‘signals’ or environmental experiences, operating during brief critical periods, have lifetime effects.
2. EVIDENCE FROM ANIMALS
Evidence that early nutrition has such ‘programming’ effects in animals is overwhelming. Adult outcomes programmed by infant nutrition include lipid metabolism, blood pressure, obesity, diabetes, arteriosclerosis, behaviour and longevity. Such programming occurs in diverse species, including primates.
14 Alan Lucas In humans, observational studies link adult disease with size or mode of nutrition in early life. Yet, it is difficult to use observational associations to prove causation, and hence underpin health policy.
However, over 20 years ago we used the pharmaceutical intervention trial model to test prospectively long term effects of early diet, randomly assigned, on health and neurodevelopmental outcomes. Given the need for long-term follow up to detect emergence of programmed effects, the major impact of early nutrition has only recently emerged.
3. STUDIES ON PREMATURE BABIES
The longest-term experimental evidence for programming is based on studies of premature babies. We showed only 2-4 weeks of randomised dietary manipulation in neonates programmes in adolescence and beyond: (1) key components of the metabolic syndrome - blood pressure, tendency to obesity and diabetes and blood lipids, (ii) the first stages of the atherosclerotic process (determined by ultrasound), (iii) brain structure and function (iv) bone health, possibly relevant to degenerative bone disease, (v) atopy. Effect sizes are large. Thus early diet has a greater effect on later cardiovascular risk factors than lifestyle modification in adulthood.
4. STUDIES ON FULL TERM INFANTS
However, programming also occurs in healthy full-term infants, through effects of specific nutrients (e.g. iron, long-chain polyunsaturated fatty acids) or whole diets (e.g. breast milk).
Importantly for some outcomes, early nutrition may operate by influencing postnatal growth. Early growth acceleration in invertebrates and vertebrates carries long term health costs. Our new experimental evidence shows in humans faster postnatal growth is a major adverse influence on later cardiovascular risk.
THE DEVELOPMENTAL ORIGINS OF ADULT HEALTH 15
5. POSTNATAL GROWTH ACCELERATION HYPOTHESIS
Relative effects of fetal versus postnatal growth need reappraisal. We suggest the postnatal period is particularly important and the risk for the small fetus may relate to deleterious postnatal growth acceleration (‘catch-up’) seen in this population. Thus the ‘fetal origins hypothesis’
may be largely explained in terms of the broader ‘growth acceleration hypothesis’.
6. A BALANCE OF RISKS
Designing optimal early nutritional policies requires balance of risks.
In premature babies, a high plane of nutrition benefits later brain development but adversely programmes cardiovascular health. Defining the corresponding balance of risks in healthy full-term infants is a critical priority.
In summary, 40 years of animal and human studies show early nutrition is a key factor for health with major biological and social implications.