Nestle Nutrition workshop series. Paediatric programme最新文献

Despite some improvements in recent years, extreme poverty and malnutrition remain a critical concern for developing countries. Malnutrition, and more specifically pediatric malnutrition, is a reality affecting millions of children, particularly in South Asia and Africa. It causes increased mortality and morbidity, decreased physical and intellectual development, poor productivity and a number of negative economic outcomes. Health economics data clearly demonstrate that interventions are effective and efficient, but more data are needed to measure that efficiency. Initiatives to address microdeficiencies have focused on vitamin A, iodine, zinc, iron and folate. Iodine is often used as a best practice example. Two main institutions lead the efforts to address malnutrition throughout the world: the UN with its UN Millennium Development Goal project, and the Copenhagen Consensus. We consider micronutrient deficiencies, particularly in iodine, corresponding interventions, their effects and health economic data. We discuss how developing public/private partnership could boost the effectiveness of interventions by combining the competencies of both sides: credibility, national and international buy-in, experience of public institutions, commercial competencies, high penetration rate, and product knowledge of private industry.

Growth assessment of children requires comparison of growth measurements with normative references, usually in the form of growth charts. Traditionally growth charts (growth references) have described the growth of children who were considered normal and were living in a defined geographic area. The new WHO growth charts, on the other hand, are growth standards that aim to represent growth as it occurs worldwide. Moreover, they represent growth as it occurs under optimal circumstances and is thought to be conducive to optimal long-term health. Most growth references are single-country references, exemplified here by charts from the UK, the Netherlands and the USA. By contrast, the Euro-Growth reference and the WHO standard are based on multinational samples. Comparison of these five charts reveals surprisingly large differences that are for the most part unexplained. Differences between the WHO charts and other charts are only partially explained by the use of a prescriptive approach and by the data truncation employed. The large differences between charts probably are of merely trivial consequence when charts are used in monitoring individual children. When charts are used in health assessment of groups of children, the impact of the differences, however, is substantial.

A large body of epidemiological data suggests that adverse early environments, including obesity during pregnancy or early postnatal life, are linked to an elevated prevalence of metabolic disease in adult offspring. The mechanisms underlying these effects are still poorly understood, but recent data from rodents provide insight into a potential role for the brain in this 'metabolic programming.' This review summarizes the developmental changes that have been observed in the hypothalamus in response to changes in the early nutritional and hormonal environment. It also discusses how resetting a diverse array of neuroendocrine systems may have long-term effects on the regulation of metabolism and energy balance.

Growth is a remarkably complex biological phenomenon, requiring the coordinated production of multiple hormones and growth factors. Human growth is characterized by several distinct features, including: (1) rapid growth in late gestation; (2) growth deceleration immediately following birth; (3) a prolonged childhood and a mid-childhood growth spurt; (4) a pubertal growth spurt; (5) relatively late attainment of adult height, and (6) minimal sexual dimorphism of adult stature. Secular changes in the height of humans probably reflect nutritional and environmental factors, rather than major genomic changes. While multiple hormones impact growth, the growth hormone (GH)-insulin-like growth factor (IGF) axis plays a central role in both intrauterine and postnatal growth. GH, after being secreted by the pituitary, binds to a transmembrane receptor and activates a postreceptor signaling cascade, ultimately leading to phosphorylation of signal transducer and activator of transcription (STAT) 5b. STAT5b transcriptionally regulates the genes for IGF-I and for key IGF-binding proteins. IGF-I, in turn, binds to the type 1 IGF receptor, resulting in chondrocyte proliferation and statural growth. IGF-deficient states may be divided into secondary forms, reflecting defects in GH production, and primary forms. Molecular defects of the GH-IGF axis have been identified in humans, with phenotypes that correspond to the specific genetic lesions. Therapy with GH or IGF-I can now be matched to specific defects in the GH-IGF axis.

A variety of systems are used to establish efficacy of food ingredients. Immortal human cell lines have the advantage of rapid throughput and often have the ability to point to mechanisms of action. Transgenic and natural variants of animals (usually rats and mice) have proven to be extremely useful in elucidating effects in vivo, although extrapolation of results to humans has risks. Animal models are also useful in establishing safety and toxic levels of ingredients. Human trials have the most relevance to society. Types of evidence for efficacy rise from improved status level in subjects as a result of eating food (long-chain polyunsaturated fatty acid, levels in erythrocytes), change in surrogate markers as a result of eating food (plasma cholesterol or glutathione peroxidase activity), change in a physiological outcome (such as visual evoked potential acuity or heart rate variability) through to the highest level of evidence, a change in a clinical outcome (improved global development, reduction in infections) established in randomized controlled trials. Ultimately, there is a need for tests of pragmatic interventions that can easily be incorporated into usual dietary practices of the culture in which it is tested.

Malnutrition remains a major problem in children in large parts of the developing world. About 150 million young children in the developing world are either wasted or stunted, and it has been estimated that over half of childhood deaths are attributable to the potentiating effects of malnutrition. Thus, tackling both mild-moderate and severe malnutrition effectively is essential if the millennium development goals are to be achieved. Intervention strategies to promote exclusive breastfeeding for about 6 months in the absence of maternal HIV infection will result in significant improvements in nutrition, and are key to prevention strategies for malnutrition. Careful evaluation and effective counseling of HIV-positive mothers regarding feeding choices is essential. Evidence from a number of randomized controlled trials shows that ready to use foods have an important role to play in the prevention and treatment of both outpatient and inpatient malnutrition. Such foods were initially produced commercially, but it has been shown, particularly in Malawi, that such foods can be locally produced at low cost. In some parts of the world, HIV is a major underlying cause of malnutrition in children and is associated with high mortality rates in those with severe malnutrition. Strategies for the prevention and treatment of children with HIV need to be escalated.

Effects of in utero and early life conditions on adult health and disease such as cardiovascular disease and type 2 diabetes are well documented by epidemiological and clinical observations. Animal models including intrauterine artery ligation, maternal restriction of iron, protein or general caloric intake, provide invaluable tools to understand mechanisms linking early growth and later diseases in adult life. In addition, the rodent model of maternal protein restriction has revealed that longevity can be influenced either positively or negatively by early growth patterns. Recent rapid advances in the ageing field using model organisms involving caloric restriction and genetic mutation as well as gene overexpression demonstrated the importance of insulin/ IGF-1 signaling pathways, oxidative damage and SIRT1 in the regulation of lifespan. Studies using rodent models of maternal protein restriction suggest that alteration in insulin metabolism, changes in expression of antioxidant defense systems and in levels of oxidative damage (including telomere attrition) may also play a key role in regulation of lifespan by the early environment. It is suggested that neuroendocrine systems and epigenetic modification may be the potential mechanisms underlying beneficial or detrimental effects of early growth on the regulation of lifespan. Further studies in this area are warranted.

The concept that early growth and nutrition have long-term biological effects is based on extensive studies in animals dating from the 1930s. More recently, compelling evidence for a long-term influence, or programming effect, of growth has also emerged in humans. Substantial evidence now supports the hypothesis that 'accelerated' or too fast infant growth increases the propensity to the major components of the metabolic syndrome (glucose intolerance, obesity, raised blood pressure and dyslipidemia), the clustering of risk factors which predispose to cardiovascular morbidity and mortality. The association between infant growth and these risk factors is strong, consistent, shows a dose-response effect, and is biologically plausible. Moreover, experimental data from prospective randomized controlled trials strongly support a causal link between infant growth and later cardiovascular risk factors. These observations suggest therefore that the primary prevention of cardiovascular disease could begin from as early as the first few months of life. The present review considers this evidence, the underlying mechanisms involved and its implications for public health.