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Foetal development and infancy are life stages that are characterised by rapid growth, development and maturation of organs and systems. Variation in the quality or quantity of nutrients consumed by mothers during pregnancy, or infants during the first year of life, can exert permanent and powerful effects upon developing tissues. These effects are termed 'programming' and represent an important risk factor for noncommunicable diseases of adulthood, including the metabolic syndrome and coronary heart disease. This narrative review provides an overview of the evidence-base showing that indicators of nutritional deficit in pregnancy are associated with a greater risk of type-2 diabetes and cardiovascular mortality. There is also a limited evidence-base that suggests some relationship between breastfeeding and the timing and type of foods used in weaning, and disease in later life. Many of the associations reported between indicators of early growth and adult disease appear to interact with specific genotypes. This supports the idea that programming is one of several cumulative influences upon health and disease acting across the lifespan. Experimental studies have provided important clues to the mechanisms that link nutritional challenges in early life to disease in adulthood. It is suggested that nutritional programming is a product of the altered expression of genes that regulate the cell cycle, resulting in effective remodelling of tissue structure and functionality. The observation that traits programmed by nutritional exposures in foetal life can be transmitted to further generations adds weight the argument that heritable epigenetic modifications play a critical role in nutritional programming.

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1. In the rat, hypertension is induced by fetal exposure to maternal low-protein diets. The effect on blood pressure of undernutrition before conception and during discrete periods in early, mid or late pregnancy was assessed using an 18% casein (control) diet and a 9% casein to apply mild protein restriction. 2. The offspring of rats fed 9% casein developed raised blood pressure by weaning age. Feeding a low-protein diet before conception was not a prerequisite for programming of hypertension. 3. Hypertension was observed in rats exposed to low protein during the following gestational periods: days 0-7, days 8-14 and days 15-22. Blood pressure increases elicited by these discrete periods of undernutrition were lower than those induced by feeding a low-protein diet throughout pregnancy. The effect in early gestation was significant only in male animals. Post-natal growth of male rats exposed to low-protein diets was accelerated, but kidneys were small in relation to body weight. 4. Biochemical indices of glucocorticoid action in liver, hippocampus, hypothalamus and lung were elevated in rats exposed to low-protein diets in utero. The apparent hypersensitivity to glucocorticoids was primarily associated with undernutrition in mid to late gestation. 5. Plasma renin activity was elevated in rats exposed to 9% casein over days 15-55 of gestation. Animals undernourished over days 0-7 and 8-14 produced pups with lower plasma angiotensin II concentrations at weaning. 6. Fetal exposure to maternal low-protein diets for any period in gestation may programme hypertension in the rat. Alterations to renal structure, renal hormone action or the hypothalamic-pituitary-adrenal axis may all play a role in the programming phenomenon, either independently or in concert.

Background:While many studies have demonstrated positive associations between childhood obesity and adult metabolic risk, important questions remain as to the nature of the relationship. In particular, it is unclear whether the associations reflect the tracking of body mass index (BMI) from childhood to adulthood or an independent level of risk. This systematic review aimed to investigate the relationship between childhood obesity and a range of metabolic risk factors during adult life.Objective:To perform an unbiased systematic review to investigate the association between childhood BMI and risk of developing components of metabolic disease in adulthood, and whether the associations observed are independent of adult BMI.Design:Electronic databases were searched from inception until July 2010 for studies investigating the association between childhood BMI and adult metabolic risk. Two investigators independently reviewed studies for eligibility according to the inclusion/exclusion criteria, extracted the data and assessed study quality using the Newcastle–Ottawa Scale.Results:The search process identified 11 articles that fulfilled the inclusion and exclusion criteria. Although several identified weak positive associations between childhood BMI and adult total cholesterol, low-density lipo protein-cholesterol, triglyceride and insulin concentrations, these associations were ameliorated or inversed when adjusted for adult BMI or body fatness. Of the four papers that considered metabolic syndrome as an end point, none showed evidence of an independent association with childhood obesity.Conclusions:Little evidence was found to support the view that childhood obesity is an independent risk factor for adult blood lipid status, insulin levels, metabolic syndrome or type 2 diabetes. The majority of studies failed to adjust for adult BMI and therefore the associations observed may reflect the tracking of BMI across the lifespan. Interestingly, where adult BMI was adjusted for, the data showed a weak negative association between childhood BMI and metabolic variables, with those at the lower end of the BMI range in childhood, but obese during adulthood at particular risk.

The environment encountered in fetal and neonatal life exerts a profound influence on physiological function and risk of disease in adult life. Epidemiological evidence suggests that impaired fetal growth followed by rapid catch-up in infancy is a strong predictor of obesity, hypertension, non-insulin-dependent diabetes and CHD. Whilst these associations have been widely accepted to be the product of nutritional factors operating in pregnancy, evidence from human populations to support this assertion is scarce. Animal studies clearly demonstrate that there is a direct association between nutrient imbalance in fetal life and later disease states, including hypertension, diabetes, obesity and renal disease. These associations are independent of changes in fetal growth rates. Experimental studies examining the impact of micro- or macronutrient restriction and excess in rodent pregnancy provide clues to the mechanisms that link fetal nutrition to permanent physiological changes that promote disease. Exposure to glucocorticoids in early life appears to be an important consequence of nutrient imbalance and may lead to alterations in gene expression that have major effects on tissue development and function. Epigenetic mechanisms, including DNA methylation, may also be important processes in early-life programming.

The aim of this cohort study was to determine whether periodontitis and gingivitis are associated with impaired salivary antioxidant status and increased oxidative injury. One hundred and twenty-nine patients attending a routine dental check-up were recruited for the study. Periodontal disease status was characterized using the Community Periodontal Index of Treatment Needs (CPITN) system. Total salivary antioxidant capacity and salivary ascorbate, urate and albumin were determined in a sample of whole unstimulated saliva. Protein carbonyl concentrations were determined as an index of oxidative injury. Patients in the lowest tertile of CPITN score exhibited decreased salivary delivery of antioxidants and specifically urate than patients in the upper tertile. Poor periodontal health was associated with increased concentrations of protein carbonyls in saliva. Women had significantly lower total antioxidant status than men, regardless of periodontal health. Periodontal disease is associated with reduced salivary antioxidant status and increased oxidative damage within the oral cavity.

Nutrient restriction in pregnancy has been shown to programme adult obesity. Modulation of feeding behaviour may provide a mechanism through which obesity may be programmed. Pregnant Wistar rats were fed either a control diet or a low-protein (LP) diet throughout gestation. Their offspring were allocated to a self-selected-diet protocol to assess appetite and food preferences at 12 and at 30 weeks of age. Self-selection of high-fat, high-protein or high-carbohydrate foods by 12-week-old rats indicated that the prenatal environment influenced feeding behaviour. Both male and female offspring of LP-fed mothers consumed significantly more of the high-fat (P,0·001) and significantly less (P, 0·02) of the high-carbohydrate food than the control animals. Female, but not male, offspring of LP-fed rats failed to adjust food intake to maintain a constant energy intake and had higher fat (P, 0·005) and energy intakes (P,0·05) than control female rats. At 30 weeks of age there were no differences in the pattern of food selection between the two groups of animals. Male offspring of LP-fed rats had significantly more gonadal fat than control animals (P,0·05), but analysis of total body fat content indicated that there was no significant difference in overall adiposity. The present study suggests that in young adults at least, early life exposure to undernutrition determines a preference for fatty foods. Maternal nutrition may thus promote changes in systems that are involved in control of appetite or the perception of palatability.