Nutrition and the Metabolic Health of Children
Overnutrition, expressed as overweight and obesity, sometimes combined with inadequate micronutrient intake, coexists together with undernutrition as the major threats of malnutrition in children. Appropriate growth and metabolism of children have been extensively studied as to their association with future metabolic diseases. It is appreciated that early growth is controlled via the biochemical pathways that support organ and tissue growth and development, energy release from dietary intake, and production and release of hormones and growth factors regulating the biochemical processes. Anthropometric measurements, body composition, and their trajectories have been the metrics to evaluate both age-appropriate growth and link to future metabolic disease risk. As factors associated with risk of metabolic disease like childhood obesity are fairly well known, a strategic framework that includes appropriate nutrition and healthy dietary habits, adoption of the right behavior, and healthy food choices from early infancy to childhood is necessary to decrease this risk. The role of industry in this is to provide foods rich in nutrients developmentally appropriate and to promote responsible consumption and age-adapted portion sizes.
Until the middle of the 20th century, the major threats to the health and wellbeing of children were linked to undernutrition and infectious diseases. While these two aspects remain important causes of ill health of children globally, it is now clear that overnutrition and its consequences represent major risks to health and that metabolic programming due to dietary or environmental factors is also a threat to health throughout the life cycle. This overview will consider the influence of nutritional factors in children’s health, starting with basic aspects of growth and metabolism, then considering the problems of underweight and undernutrition, followed by the challenges caused by overweight and obesity.
Growth and Metabolism
Normal Physical Growth – Early Milestones
In children above 1 year of age, the body mass index (BMI) can be used as an index of growth of the whole body as it is determined by weight divided by height (or length) squared. While there are benefits to be gained from looking at age-related increases in height and increases in weight separately, BMI provides an index which depends on both height and weight, and which is also following a specific trajectory over time. Thus, rather than the actual BMI, it is normally the z-score (or multiples of the standard deviation of the BMI at a given age) that is used to compare children or to assess changes over time. In term babies, there is a rapid increase in BMI between 7 and 12 months or so of life. This increase from a BMI of approximately 11.5 at birth to 17 over a 9-month period is the most rapid seen during any stages of the life cycle. Clearly, if the BMI is increasing at such a rapid rate, there is a substantially greater increase in weight than height (length). Over the next 3–4 years, there is a steady decline in BMI as linear growth occurs more rapidly than weight, such that around the age of 4–5 years, the BMI is at a nadir of approximately 15–16. During this period of early childhood, there is also a greater increase in fat-free mass than in fat mass, so the percentage of body fat falls from infancy to age 5–6 years. This nadir of BMI is then followed by the start of the adiposity rebound  when a slower increase in BMI occurs over the next 12–13 years, with increases in height and weight, with both fat mass and fat-free mass increasing over this period. Included in this period is the adolescent growth spurt and the differences in fat and fat-free mass increases in relation to sex, but these aspects are beyond the context of this overview. By the age of 18 year, the BMI will be approximately 21.5 in healthy, well-nourished individuals, although undernutrition and overnutrition during childhood and adolescence can lead to low or high BMI values outside the healthy range.
Rolland-Cachera et al.  proposed that if the adiposity rebound occurs at 4–5 years, or before, then there is a more rapid increase in adiposity and an increased risk of obesity in childhood, adolescence, and adulthood. More recent evidence has shown that infant growth in the first 6 months of life is slower if the baby is breastfed compared to formula . However, as weaning occurs, there is a faster rate of growth between 6 and 12 months if the guidance to include fresh fruit and vegetables plus home-prepared food and continued breastfeeding is followed, compared to those infants receiving breads and processed foods during weaning . While this could just be a consequence of the slower weight gain in the first 6 months, it is important to recognize that the more rapid weight gain in the second 6 months may not always be beneficial as a literature review by the same authors had previously reported that larger infants or those showing faster infant growth were at increased risk of obesity as children . Differences in body composition trajectories may explain the dynamics of these associations further. Formula-fed infants have been consistently described to have higher accretion of lean mass during the first few months of life, while their fat mass at later age was higher compared to breastfed infants [4, 5].
Metabolic Health and Relevant Growth in Early Life (Fig. 1)
The essential components of metabolism include the biochemical pathways that support organ and tissue growth and development, the release of energy within the cells from the dietary macronutrients, and the production and release of hormones and growth factors to regulate the biochemical processes. The brain is dependent on an adequate supply of glucose as a fuel for aerobic metabolism to support brain growth, development, and function, in infants and young children, and so effective glucose homeostasis is a critical aspect of metabolism and growth in early life.
The link between metabolic health and optimal growth in early life is clearly dependent on an adequate and age-appropriate diet, and both undernutrition and overnutrition in early life can have a major impact on growth and subsequent health in childhood, adolescence, and adulthood. These undesirable effects of nutrition can have epigenetic effects within the infant, which lead to long-term impact on the organs and functions due to modifications of the genes involved in the regulation of these metabolic pathways. It was originally thought that the main epigenetic influences occurred during fetal life, and low or high birthweight is a major risk factor for later chronic disease, but under- and over-nutrition in infancy can also lead to epigenetic changes with long-term consequences .
Thus, an adequate nutrient supply is critical to provide the building blocks for growth, the substrates for energy metabolism, and the precursors for signaling molecules, hormones, and the specialized components of the vital organs. It is obvious that an inadequate supply of these dietary components will compromise growth and metabolism, and oversupply of energy is likely to lead to excess fat accumulation and obesity. However, it is less obvious that an excessive intake of protein in infancy in an otherwise balanced diet can cause problems for the child. Koletzko and colleagues  performed a randomized controlled trial of dietary protein content in infants for the first year of life and looked at the effect on height and weight at 2 years of age. The dietary groups received either lower protein (1.77 and 2.2 g protein per 100 kcal in infant formula and follow-on formula) or higher protein (2.9 and 4.4 g protein per 100 kcal) in the first year, with these formulas all based on cow’s milk and the allocations being blinded to the parents. A comparator group of breastfed infants was also studied. The outcome was that the lower protein group had a lower weight for length z-score at 2 years than the higher protein group and that the lower protein group value was no different from the breastfed group (although this aspect was not randomized, so caution is needed in drawing conclusions). The dietary protein content did not affect length, so the major effect was that the higher protein group had a higher weight for length and higher BMI z-scores from 6 months of age. Children in the high protein formula arm had significantly higher BMI compared to those in the low formula arm at 6-year follow-up with the strongest effects driven by the group at the 90th percentile .
The impact of fetal and infant undernutrition is not just restricted to growth and metabolism but can also affect the cardiovascular system and the associated risk of cardiometabolic disease. A study by Belfort and colleagues  looked at relationships between weight and length in babies at birth, 6 months, and 3 years and systolic blood pressure (SBP) at 3 years. The babies in the highest quartile of weight for length z-score at birth had the lowest SBP at 3 years. Of great interest is that those babies in the lowest quartile of weight for length z-score at birth but who had the largest increase in weight for length z-score from birth to 6 months had the highest SBP at 3 years. In fact, the SBP at 3 years of those in the lowest birth but highest 6 month weight for length quartiles was 5.5 mm Hg higher than those starting in the highest quartile but then in the lowest quartile at 6 months. Thus, the consequences of low birthweight followed by rapid infant growth may have undesirable long-term effects on the cardiovascular system. A more recent study used the NHANES database to assess the association between reported birthweight and measured SBP in children aged up to 15 years at the time of the blood pressure measurement . They observed that low birthweight was associated with higher SBP, irrespective of current BMI. The association of low birthweight and high SBP was stronger in boys than in girls and accompanied by lower HDL cholesterol, whereas in girls, low birthweight was associated with higher HbA1c, an indicator of impaired glucose homeostasis.
Figure 1 shows the microbiome as one of the aspects of metabolic health and growth in early life. The potential role of the gut microbiota in healthy growth and metabolism is based on observational data and some preclinical research. From this work, it seems likely that the gut microbiota has an important influence on gut barrier function and related immune function, on whole body metabolism through the impact of short-chain fatty acids generated by bacterial fermentation, and also on secretion of some hormones, particularly the gut hormones. Breast milk contains oligosaccharides, which are potential substrates for some of the microbiota and which may modulate these beneficial effects. However, there is a need for carefully designed intervention trials with clear physiological outcomes to demonstrate mechanistic links between the microbiota, potential substrates (prebiotics), and benefit to the individual.
Tracking of Physical Growth
Geserick et al.  reported an important prospective study in over 50,000 children from 0 to 14 years. They reported that most of the adolescents with normal weight had always had a normal weight throughout childhood. About 50% of the children who were overweight at 2 years or less moved into the normal weight category in adolescence. However, 90% of the children who were obese at the age of 3 years were either overweight or obese as adolescents. Furthermore, the most rapid weight gain in those who were obese as adolescents was seen between 2 and 6 years. These observations provide a clear framework for identifying infants and young children at risk of becoming obese adolescents and subsequently adults and who are likely to benefit from an effective weight management program from early childhood, accounting for underlying risk factors such as maternal health and pregnancy complications and their growth trajectories during the first year of age.
The changes in adipose tissue content during gestation, infancy, childhood, and adolescence have been recently reviewed by Orsso and colleagues . As one would expect from maternal weight gain, the greatest increase in adipose tissue in gestation is in the third trimester, and they reported growing evidence of the influence of maternal nutrition, toxins, and genetic factors on adipose tissue deposition. In the neonatal period, there are rapid increases in adipose tissue in the first 6 months after birth, following which in infancy the adipose tissue stores normally decrease at the same time as linear growth and fat-free mass accretion increase. The changes in adipose tissue in infancy are affected by nutritional factors and feeding practices (breast or formula feeding as indicated above), as well as the gut microbiome, and these are potential targets for future initiatives to prevent excessive fat deposition and childhood obesity. Adipose tissue expansion is relatively slow during childhood until the onset of puberty, when there are major sex differences, with girls having an increase in adipose tissue and boys having a relative reduction as muscle mass expands.
Underweight and Undernutrition
As indicated earlier, these two factors have been of major concern when considering healthy childhood growth in many parts of the world. A number of factors need to be considered before initiating major nutritional interventions because there are occasions when this is not justified or likely to be effective. For example, is the child small for their height or are they just short with an appropriate weight? If the latter, then a simple nutritional intervention is unlikely to be very effective and endocrine therapy may be appropriate. Has the child progressively dropped down the centiles on the growth charts or have increasingly negative z-scores on the weight for height charts? This is a matter of some concern and may be due to an inadequate diet which would need further investigation. It is also possible that endocrine intervention plus dietary therapy may be justified.
A major concern, indicated in the previous section, is the child who is underweight at birth but then has rapid weight gain as an infant. Some of this is clearly catch-up growth and may not have long-term negative effects on health, but continued rapid growth is a concern and likely to be a risk factor for obesity in childhood and adolescence and careful monitoring is needed.
Chronic undernutrition in children is a major worry as it can lead to major disturbance of growth, but also of development, like brain development, if the diet is limited in quantity and/or in its micronutrient content. For example, inadequate iodide intake will impact on thyroid status and not just affect cell metabolism but also limit neurodevelopment in fetal and neonatal periods and infancy
It is now clear that a number of factors are major risks for the development of obesity in childhood. Maternal impaired metabolic health and high BMI, using infant formula rather than breastfeeding and early weaning, are risk factors for excessive weight gain in infancy. High intake of sweetened beverages, low intake of fruits and vegetables, habitual consumption of foods outside the home, and lack of family meals are major risk factors for excessive weight gain in childhood. In addition, low sleep duration at night, excessive TV or screen viewing time, and low levels of active play have all been identified as contributing to the risk of obesity in childhood.
One overarching factor that has been found to markedly increase the risk of childhood obesity is social deprivation. This has been clearly demonstrated in England, where the National Child Measurement Programme has measured the height and weight of almost all school children aged 5–6 and 10–11 years annually since 2006. The data from 2018 illustrate the concerns regarding deprivation, where in the 5- to 6-year-olds, the least deprived boys and girls have shown progressive reductions in the prevalence of overweight and obesity over a 12- year period, whereas the most deprived quintile has shown progressive increases in prevalence over this time period. Deprivation was defined using the Index of Multiple Deprivation, the official measure of relative deprivation in England. Deprivation deciles are calculated by ranking the 32,844 neighborhoods in England from most deprived to least deprived and dividing them into 10 equal groups . Interestingly the impact of deprivation was more noticeable in the young girls than the boys, as the girls showed no reduction in prevalence over time in the third, fourth, and fifth most deprived quintiles, whereas it was only the most deprived quintile in the boys that showed no change in prevalence. The older children (10–11 years) had higher rates of obesity and overweight than the younger children, but again the most deprived quintile showed a progressive increase in prevalence over the 12 years, whereas the least deprived showed a reduction . Recent reports from the COVID-19 pandemic provide a credible example on how social deprivation combined with disrupted routine and stress led to an almost double-digit increase rate in BMI particularly within young children with overweight or obesity pre pandemic .
Role of Industry
Everyone has a role to play in dealing with the obesity epidemic, and this includes the food industry. There is a real risk that if industry does not define a role in helping countries and individuals to reduce the incidence of obesity, then it may be defined for them. In some sectors, there are concerns about the social irresponsibility of promoting large portions and energy-dense foods and failing to help consumers eat healthily as part of an active lifestyle.
As indicated above, undesirable dietary practices associated with obesity risk are already present in some infants. By 2 years of age, the child has already assumed the eating practices of the family and BMI at 3 years is predictive of obesity in childhood and later life. Reidy and colleagues  published a detailed analysis of the 2008 Feeding Infants and Toddlers Study (FITS), which was a cross-sectional survey of dietary intake in US children aged 0–47 months. They showed that the diet transitioned from being entirely milk based (as expected) to having a fairly stable pattern from 18 to 47 months, which was low in fruits and vegetables and high in grains, meat, and sweet foods. In fact, the contribution of sweet foods exceeded the combined contribution of fruits and vegetables. Recent evidence also states that dietary patterns, including sugar-rich, ready-to-eat, and confectionary products, initiated during infancy track up to mid-childhood with potential long-term consequences on metabolic health .
The main priorities for childhood nutrition are now early recognition/identification of risk, prevention of undernutrition, providing appropriate nutrients for effective immune function to deal with infectious diseases, reduction of the risk of obesity, and help for those already overweight or obese to return toward a healthy weight. The impact of overnutrition on metabolic programming is at least as important as the effect of undernutrition, and the possibility that both of these can lead to epigenetic changes, which will make reversal of impaired health much more challenging.
The food industry can make a major contribution to enable children to achieve healthy growth and health by the provision of nutrient rich-foods and promoting responsible consumption and appropriate portion sizes. However, the industry also needs to recognize that inappropriate consumption of energy rich and nutrient-poor foods can contribute to the development of obesity and to specific nutrient inadequacies. A major challenge going forward is to develop a strategy to help children and their caregivers make appropriate choices for the long-term health of the child.
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