Nutrition and Growth

Editor(s): R. Shamir, D. Turck, M. Phillip.

Growth as an indicator of health is more sensitive than commonly believed and can serve as an early sign of imbalance, before other malfunctions manifest themselves. Particularly in developing countries, growth failure in infants and children is related to mortality, morbidity and impaired brain development, and increases the risk of adult-onset non-communicable diseases. This publication focuses on the challenges of the interaction between nutrition and growth in the pediatric age group. Subjects covered include the interplay between nutrition and the IGF axis; early feeding and later growth; growth charts (including an update on the implementation of the WHO growth standards); various aspects of obesity; nutrition and growth of premature infants and of children with specific diseases; and the interaction between bone health, nutrition and growth. © All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronically or mechanically, including photocopying, recording, micro copying, or by any information storage and retrieval system, without permission in writing from the publisher.

Articles

Lessons Learned from Clinical Studies on Infant Nutrition

Author(s): H. Szajewska

Currently, one of the scientific concepts is that maternal, fetal, and infant nutrition may have implications for infant size and growth and subsequently for the risk of developing chronic diseases later in life, in addition to genetic, environmental, and behavioral factors. As a consequence, the interest of scientists and policy makers is now focused on characterizing the optimal dietary patterns and patterns of prenatal and postnatal size/growth. The objectives of this paper were to briefly review/summarize: (1) evidence of the importance of size and growth as well as early nutrition for health and development, (2) methodological issues associated with current scientific approaches that evaluate the impact of early nutrition/growth on later outcomes, (3) recent regulations and guidelines developed by various expert groups or scientific organizations, and (4) ways to solve someunresolved issues.

Growth Outcome Nutritionist Perspective

Author(s): C. Agostoni, G. Fattore

Increasing evidence points to a fundamental role of early nutrition on rates of growth and development, and later health. We may identify three major fields of scientific interest and clinical application. (1) In developing countries poor growth is associated with greater risk of morbidity and mortality from infectious diseases, mainly lower respiratory infections and diarrhea. In these settings, failure to promote compensatory growth may have negative short- term consequences, and the nutritionist’s task is the primary prevention of nutrient deficiencies to promote the full expression of the individual genetic potential, while allowing for recovery of early secondary functional deficiencies. (2) A second challenge for nutritionists is represented by the approach to growth impairments in rare disorders, ranging from congenital disorders to chronic infections. Most disorders are favorably influenced by improved nutritional status and better growth, and patients may satisfactorily reach adolescence, pubertal and reproductive age, up to ageing. Even for the less positive conditions, an improvement in the quality of life for families is in any case a rewarding aim. (3) A third challenge is represented by the definition of the role of nutrition on growth in physiological conditions for all individuals. Concern has been raised about the potential adverse long- term consequences of accelerated child growth rates, possibly resulting in a predisposition to develop non- communicable chronic diseases in the adult age. Accordingly, this hypothesis might explain the benefits of breastfeeding in terms of slower early growth, and the fetal origins hypothesis in terms of adverse postnatal catch- up growth in infants born small. Therefore, growth as viewed by a pediatric nutritionist perspective is a complex matter, ranging from the early stages of intrauterine development up to adult ages and ageing processes. Cost/benefit analyses of interventions on growth such as cost per DALYs (disability- adjusted life years) or QALYs (quality- adjusted life years) should be expanded on population basis and extended also to congenital and invalidating disorders to identify the most effective and economic sustainable strategies of action.

Nutritional Biomarkers for Growth Outcomes Perspective of the Endocrinologist

Author(s): M. Yackobovitch-Gavana, G. Gat-Yablonskia, M. Phillip

Linear growth is a hallmark of childhood; in most cases it proceeds without interference until final height is achieved after puberty. However, numerous genetic and environmental factors may interfere with the normal process. One of the most common environmental factors that may affect linear growth is the nutritional status. Due to the significant influence of nutrition on childhood’s growth, the identification of good nutritional biomarkers for growth outcomes will potentially help the pediatric endocrinologist to improve diagnosis and treatment of nutritional growth attenuation. This paper will discuss the following questions: What is a good nutritional biomarker for growth outcomes? Which nutritional biomarkers are already known? What additional biomarkers does theendocrinologist need?

Early Nutrition and Later Outcomes in Preterm Infants

Author(s): N. Embleton

The developmental origins of health and disease is an emerging area of interest that amalgamates many areas of scientific studies and encompasses a wide range of diverse disciplines from epidemiology to molecular biology. Evidence has accumulated to show that early life experiences, both in utero and in infancy have long- term effects on many body systems. There are now good data to show that suboptimal in utero growth, especially when combined with rapid growth acceleration in early postnatal life may increase the risk of later life metabolic disease. The mechanisms are complex but likely to involve epigenetic marks such as DNA methylation. Preterm infants frequently experience suboptimal nutrient intakes in early postnatal life and exhibit growth failure within the NICU. They also receive products that may not provide either an optimal quantity or quality of nutrients. Follow- up studies have now shown much higher risks for long- term chronic disease in children and adults who were born preterm. There are higher levels of insulin resistance and abnormal partitioning of fat deposition. The onset of puberty seems earlier, average height is less and blood pressure, measures of vascular health and lipid profiles suggest cardiovascular health is likely to differ from healthy term born controls. Despite this, there are no data to suggest an overall benefit of limiting nutrient intake, or restricting growth in preterm infants. There are strong data to show that the preterm brain is exquisitely vulnerable to undernutrition, and that suboptimal nutrient intakes may permanently affect later cognitive attainment. A clinical focus on early nutrient intakes and breast milk provision is key to optimising long- term health outcomes.

Evaluation of Growth and Early Infant Feeding A Challenge for Scientists, Industry and Regulatory Bodies

Author(s): F. Haschke, P. Steenhout, D. Grathwohl, E. Haschke-Becher

Growth studies are necessary to prove safety and efficacy of new or renovated infant formulas. Healthy infants need to be followed in randomized clinical trials until 4– 6 months of age. Breastfed reference groups should be included in such studies, because growth of formula- fed infants may deviate from breastfed infants. The WHO growth standard describes growth of exclusively or predominantly breastfed infants and is frequently used as reference. However, the limitations of the standard must be known because weight- for- age until 6 months is higher than in all international growth references. Meta- analyses indicate that both weight and BMI of breastfed reference groups in clinical trials and of infants fed a low protein formula are somehow lower than the WHO standard. Infants of overweight and obese mothers or at risk for malnutrition are considered as at- risk populations. Any infant formula trial in those populations should use the WHO standard to document safety.

Bone Mineral Accretion and Its Relationship to Growth, Sexual Maturation and Body Composition during Childhood and Adolescence

Author(s): B. Zemel

Bo ne mineral accretion during childhood and adolescence is subject to a number of influences, including body composition changes, sexual maturation and growth. Bone mass and density increase with age and vary by sex, so bone health must be evaluated like other growth outcomes, i.e. in relation to age- and sex- specific reference ranges. Peak bone mass, the amount of bone acquired at the end of skeletal development is an important determinant of lifelong skeletal health. The timing of puberty is inversely related to peak bone mass, such that individuals who experience puberty at older ages have lower bone mass in young adulthood. Height, an indicator of skeletal size, is correlated with bone mineral content and density. Even more importantly, children who are tall for their age have greater bone mass and density than children of average or short stature. Body composition, particularly lean body mass, has a positive effect on bone accretion because of the mechanical strains of muscle mass on bone accretion. The effect of height growth is positively associated with bone accretion, but the magnitude of the effect is not the same at all pubertal stages; in Tanner stage 5, height growth has a more pronounced effect on bone accretion than at the beginning of puberty. Understanding these complex relationships is essential to understanding bone metabolism during this part of the life cycle and the challenges of assessing bone health in children with medical conditions that threaten bone health.

Prenatal Nutritional Influence on Skeletal Development

Author(s): E.Curtis, J. Cheah, N. Harvey

There is increasing evidence to suggest that prenatal nutritional factors may have long- term effects on the offspring. Osteoporosis is a worldwide public health problem leading to both morbidity and mortality, through associated bone fractures. Although in clinical practice most effort in fracture prevention is aimed at slowing the rate of age- related bone loss, there is accumulating evidence that peak bone mass, achieved in early adulthood, is an important factor in determining bone strength in later life. A variety of studies have shown that peak bone mass is influenced by early life events, including nutrition in the prenatal period. This chapter will use the example of bone development to consider the effects of maternal diet and nutritional status on the offspring.

Insulin- Like Growth Factors, Nutrition and Growth

Author(s): M. Savage

Nu tritional status is a key factor in the regulation of human linear growth. The growth hormone (GH)- IGF axis consists of a cascade of finely tuned molecular mechanisms which are vulnerable to proteincalorie deficiency. The most notable evidence for this is the presence of IGF- 1 deficiency, that can be caused by failure of a number of processes including abnormal pituitary GH secretion, decreased GH binding to its receptor (GHR), post- GHR signal transduction, IGF- 1 gene  transcription, IGF binding protein (IGFBP) deficiency and decreased IGF- 1 binding to its own receptor (IGF1R). Nutritional deficiency is seldom present as an isolated pathogenesis. In diarrhoeal states, intercurrent infection is frequently present which impairs the function of the growth plate. In chronic inflammatory disorders, where nutritional deficiency may be present due to increased energy expenditure, co- existing excess cytokine production also disrupts the GH- IGF- 1 axis causing a complex mixed pathogenesis.

Role of Insulin- Like Growth Factors in Growth, Development and Feeding

Author(s): J. Wit, M. Walenkamp

Information about the role of insulin- like growth factors (IGFs) is mainly derived from knockout (KO) and transgenic mice, human mutations in IGF1, IGF1R and IGFALS, and association studies with IGF1 SNPs. Igf1 KO mice show severely impaired pre- and postnatal growth and brain development and sensorineural hearing loss. Both local and endocrine IGF- 1 are needed for normal growth. Igfals KO mice show a modest postnatal growth attenuation. Homozygous igf1r KO mice are severely growth impaired, while heterozygous mutations only show mild growth retardation. Two patients with a complete absence of biologically active IGF- 1 showed severe pre- and postnatal growth, extreme microcephaly, sensorineural deafness and failure to thrive. A patient with a mutation that led to a partially functional protein had a less severe growth phenotype and no deafness, similarly to two siblings with a heterozygous IGF1 mutation. Heterozygosity for a dysfunctional IGF1 mutation leads to a mild effect on birth weight, adult height and head circumference. Patients with heterozygous mutations or deletions of IGF1R have a moderate pre- and postnatal growth failure, microcephaly and a history of feeding problems. Children with homozygous mutations of IGFALS have a low or normal birth weight, a mild growth failure, a head circumference in the lower normal range, and no failure to thrive. Association studies of IGF1 polymorphisms in large populations have shown variable results with respect to height, but a more consistent association with head circumference. In conclusion, a normal IGF- I bioactivity (normal local and endocrine IGF- 1 availability, normal IGF1R function, normal signaling) is needed for a ormal pre- and postnatal longitudinal and cranial growth. IGF- 1 dysfunction causes severe growth failure, while heterozygous defects of IGF1R and homozygous defects of IGFALS are associated with a milder phenotype. Feeding disturbances in infants with IGF1 and IGF1R mutations suggest a role of IGF- 1 signaling in regulatory brain centers.

Advances in Growth Chart Design and Use The UK Experience

Author(s): C. Wright, A. Williams, T. Cole

As part of the process of adopting the WHO standard in the United Kingdom, the Royal College ofPaediatrics and Child Health (RCPCH) was commissioned by the UK Department of Health to design new UK- WHO growth charts. The working group for this project combined expertise ranging from statistics and graphic design to qualitative research, as well as paediatrics, nursing and dietetics. New charts for children under 4 years were published in 2009 and are now widely used in the UK and beyond (www.growthcharts.rcpch.ac.uk). This paper will describe what we have learned in general about the process of designing charts and how these principles were applied to the design of a novel chart designed specifically for sick and premature infants. A successful design first requires clarity about the exact purpose of the chart and who will use it. The layout of the chart can then be varied in many ways to fit that use and ensure users are not misled. Users need consistent and well- evidenced rules for chart use. Drafting the instructions serves as a powerful test of the validity and clarity of the design. However, charts need also to be formally evaluated, as expert views will not reflect those of the average user. The Neonatal and Infant Close Monitoring (NICM) chart included various novel design features, including date boxes for gestational age adjustment and low SD lines to help assess very small infants. It was evaluated at three stages using plotting exercises and each phase led to substantial design changes. Growth charts are conceptually very complex, with the capacity to mislead as well as inform and should always be formally evaluated before implementation.

Update on the Implementation of the WHO Child Growth Standards

Author(s): M. de Onis

In 2006, the World Health Organization (WHO) launched new growth standards for application to allchildren regardless of ethnicity, socioeconomic status and feeding mode. By April 2011, 125 countries had adopted the WHO standards, another 25 were considering their adoption, and 30 had not adopted them. Reasons for adoption included: (1) providing a more reliable tool for assessing growth that is consistent with the Global Strategy for Infant and Young Child Feeding; (2) protecting and promoting breastfeeding; (3) enabling monitoring of malnutrition’s double burden, stunting and overweight; (4) promoting healthy growth and protecting the right of children to reach their full genetic potential, and (5) harmonizing national growth assessment systems. In adopting the new standards many countries switched from weight- for- age only to multiple indicators. Weight- for- age was adopted almost universally, followed by length/height- for- age (104 countries) and weight- for- length/height (88 countries). Several countries (36) reported newly introducing body mass index- for- age. Most countries opted for sex- specific charts and the z- score classification. Many redesigned their child health records and updated recommendations on infant feeding, immunization and other health messages. The scrutiny that the WHO standards have undergone is without precedent in the history of developing and applying growth assessment tools. Governments set up committees to scrutinize the new standards before deciding to adopt them and professional groups conducted thorough examination of the standards. The detailed evaluation allowed to assess the impact of the new standards and document their robustness and benefits for child health programmes. In sum, 5 years after their release, the WHO growth standards have been widely implemented. Countries have adopted and harmonized best practices in child growth assessment, and established the breastfed infant as the norm against which to assess compliance with children’s right to achieve their full genetic growth potential.

Nutritional Catch-Up Growth

Author(s): G. Gat-Yablonski, R. Pando, M. Phillip

Malnutrition, marked by variant nutrient deficiencies, is considered a leading cause of stunted growthworldwide. In developing countries, malnutrition is caused mainly by food shortage and infectiousdiseases. Malnutrition may also be found in the developed world, where it is due mostly to prematurity, chronic diseases, and anorexia nervosa. In most cases, when food consumption is corrected, spontaneous catch- up (CU) growth occurs. However, CU growth is not always complete, leading to growth deficits. Therefore, it is important to understand the mechanisms that govern this process. Using a rat model of food restriction followed by refeeding, we established a nutrition- induced CU growth model. Levels of leptin and insulin- like growth factor- 1 were found to significantly decrease when food was restricted and to increase already 1 day after refeeding. Gene expression analysis of the growth plate revealed that food restriction specifically affects transcription factors such as the hypoxia inducible factor- 1 and its downstream targets on the one hand, and global gene expression, indicating epigenetic regulation, on the other. Food restriction also reduced the level of several microRNAs, including the chondrocyte- specific miR- 140, which led to an increase in its target, SIRT1, a class III histone deacetylase. These findings may explain the global changes in gene expression observed under nutritional manipulation. We suggest that multiple levels of regulation, including transcription factors, epigenetic mechanisms, and microRNAs respond to nutritional cues and offer a possible explanation for some of the effects of food restriction on epiphyseal growth plate growth. The means whereby these components sense changes in nutritional status are still unknown. Deciphering the role of epigenetic regulation in growth may pave the way for the development of new treatments for children with growth disorders.

Growth Faltering in Low- Income Countries

Author(s): A. Prentice, S. Moore, A. Fulford

Meta- analysis of growth data from over 50 low and low- middle income countries shows a consistent pattern of stunting and poor weight gain from about 3 months of age and persisting until at least 5 years. Children tend not to be wasted because their short stature offsets their underweight, leading to a rather adequately proportioned appearance. This frequently conceals the true levels of malnutrition in communities. At the macro- environmental level such growth faltering is due to the combined effects of poverty, food insecurity, low- dietary diversity, a highly infectious environment, poor washing facilities and poor understanding of the principles of nutrition and hygiene. These tend to be ameliorated as communities pass through the demographic transition with improved incomes and education. Because such changes will take generations to achieve, the global health community continues to search for effective interim solutions. Disappointingly, apart from intensive feeding programmes aimed at rehabilitating severely malnourished children, there are few examples of very successful nutrition interventions. This emphasizes the need for a better understanding of the etiology of growth failure. This paper uses anthropometric data collected over 6 decades in subsistence farming communities from rural Gambia to illustrate the typical key features of growth faltering. Arising from this analysis, and from gaps in the published literature, the following issues are highlighted as still requiring a better resolution: (1) the pre- natal and inter- generational influences on growth failure; (2) the ontogeny of the infant immune system; (3) the exact nature of the precipitating insults that initiate gastroenteropathy; (4) the effects of both enteric and systemic infections on the hormonal regulation of growth; (5) interactions between macro- and micro- nutrient deficiencies and infections in causing growth failure, and (6) the role of the microbiome in modulating dietary influences on health and growth.

Catch- Up Growth Cellular and Molecular Mechanisms

Author(s): G. Finkielstain, J. Lui, J. Baron

In m ammals, after a period of growth inhibition, body growth often does not just return to a normal rate but actually exceeds the normal rate, resulting in catch- up growth. Recent evidence suggests that catch- up growth occurs because growth- inhibiting conditions delay progression of the physiological mechanisms that normally cause body growth to slow and cease with age. As a result, following the period of growth inhibition, tissues retain a greater proliferative capacity than normal, and therefore grow more rapidly than normal for age. There is evidence that this mechanism contributes both to catch- up growth in terms of body length, which involves proliferation in the growth plate, and to catch- up growth in terms of organ mass, which involves proliferation in multiple nonskeletal tissues.

Treatment Options for Children with Monogenic Forms of Obesity

Author(s): I . Aldhoon Hainerová, J. Lebl

Mutations in genes involved in energy balance regulation within the central nervous system lead tomonogenic forms of obesities. Individuals with these mutations are characterized by early- onset obesity and in some cases by endocrine abnormalities. Carriers of leptin gene mutations are able to normalize their body weight after daily subcutaneous leptin administration. Pharmacotherapy targetingthe specific- gene deficiencies has not clinically been tested in other monogenic obesities. Mutations in the melanocortin 4 receptor gene (MC4R) represent the most common monogenic cause of human obesity. Several treatment options have been investigated in subjects with MC4R mutations. Few studies showed that an intensive life- style intervention induces similar weight reduction in MC4R mutation carriers in comparison to MC4R mutation noncarriers. However, long- term body weight maintenance is hardly ever achieved in MC4R mutation carriers. Sibutramine, serotonin and noradrenalin reuptake inhibitor, in MC4R mutation carriers induced weight reduction and  improved cardiometabolic health risks. This result was also found in our homozygous MC4R mutation carrier. In vitro studies of melanocortin agonists efficiently activate mutated MC4R with impaired endogenous agonist functional response and thus, further research in the development of drugs for MC4R mutations is needed. An administration of intranasal adrenocorticotropic hormone was not shown to be effective in subjects with pro- opiomelanocortin gene mutations. Bariatric surgery has also been performed in few of MC4R mutation carriers. After gastric banding, lower body weight reduction and worse improvement of metabolic complications was found in MC4R mutation carriers versus noncarriers. However, preliminary results suggest that diversionary operations as gastric bypass represent a suitable method also for MC4R mutation carriers. In conclusion, the management of monogenic obesities still remains a challenge.

Early Diet, Insulin- Like Growth Factor- 1,Growth and Later Obesity

Author(s): K. Michaelsen, A. Larnkjaer, C. Molgaard

There is increasing evidence that factors in early life are important for the risk of developing overweight and obesity later in childhood. Among the postnatal factors, breastfeeding and complementary feeding are especially interesting because the pattern of these two factors can be changed. Breastfeeding has been shown to reduce the risk of later obesity, although the effect is not substantial. Complementary feeding also seems to play a role. There is some evidence that a high protein intake is associated with a higher risk of obesity later in childhood, whereas a high fat intake during the complementary feeding period does not seem to be a risk factor for later obesity. Thus, the dietary pattern during this period is different from the pattern seen in older children and adults where a high fat intake is associated with a higher risk of obesity and a high protein intake in some studies seems to protect against obesity. A few studies have also suggested that early introduction of complementary foods (before age 4 months) is associated with an increased risk of later obesity. A high weight gain during early life, especially the first 6 months, is associated with a higher risk of developing obesity. However, some studies suggest that weight gain during the 6- to 12- month age period, when complementary feeding is introduced, is not associated with later obesity. Insulin- like growth factor- 1 (IGF- 1) values and body composition both play a role in the complex pattern between early diet and later obesity, but our present knowledge about how these factors are influenced by diet during infancy is limited. Future studies should include longitudinal data on IGF- 1 and body composition during infancy to improve our understanding of how diet in early life can play a role in prevention of later obesity.

Obesity Prevention in Children

Author(s): L. Moreno, S, Bel-Serrat, A. Santaliestra-Pasías, G. Rodríguez

The prevalence of childhood overweight and obesity continues to be unacceptably high and of public health concern in Europe. During childhood and adolescence, environmental factors are the main drivers of obesity development. Obesity is caused by a chronic energy imbalance involving both dietary intake and physical activity patterns. Several risk factors are influencing obesity development, even starting in the prenatal period. From birth, along life, mainly diet and physical activity/inactivity are the most important drivers on top of genetic susceptibility. The first years of life can therefore be crucial to start preventive interventions that can have an impact on lifestyle and onlater overweight and obesity. Schools are an attractive and popular setting for implementing interventions for children. Interventions including a community component are considered to be the most effective. Obesity control will require policy interventions to improve the environments that promote poor dietary intake and physical inactivity rather than individually focused interventions. More solid institutional and health policies are needed together with more effective interventions to obtain evident changes for the prevention of excess adiposity among children.

Growth Trajectories Associated with Adult Obesity

Author(s): M. Rolland-Cachera, S. Péneau

The influence of early life factors on later body weight and metabolic diseases has generated increasing interest in the recent years. Exposure to environmental factors during pregnancy and early life can exert long- lasting influence on health. Anthropometric indicators are of great value to investigate the early determinants of the development of obesity. Different indicators may be associated with different growth patterns and then may predict different risks. The adiposity rebound (AR) which corresponds to the second rise in BMI that occurs at around 6 years of age, predicts later body weight. An early rebound is a risk factor for later overweight. Many fat children stay fat but, by contrast, an early AR is not associated with overweight in early life. These observations point out the existence of various BMI patterns associated with adult obesity. Two main trajectories emerge: the trajectory of high BMI at all ages which reflects both high lean and fat body masses, and the trajectory of low or normal BMI followed by an early AR and a subsequentrise in BMI reflecting increased fat rather than lean body mass. The trajectory of always high BMI could correspond to the so- called ‘metabolically healthy obese subjects’ while the trajectory of low BMI followed by increasing fatness is associated with insulin resistance and coronary heart diseases. The very early rebound recorded in most obese subjects suggests that determinants of obesity have operated very early in life. The identification of growth trajectories is of great interest to investigate the factors promoting obesity and metabolic diseases and to improve prevention strategies which should start from early life.

Obesity and Growth during Childhood and Puberty

Author(s): M. Loredana Marcovecchio, F. Chiarelli

Growth during childhood and adolescence occurs at different rates and is influenced by theinteraction between genetic and environmental factors. Nutritional status plays an importantrole in regulating growth, and excess body weight early in life can influence growth patterns.Childhood obesity is a growing and alarming problem, associated with several short- term and long- term metabolic and cardiovascular complications. In addition, there is evidence suggesting that excess adiposity during childhood influences growth patterns and pubertal development. Several studies have shown that during prepubertal years obese children have higher height velocity and accelerated bone age compared to lean subjects. However, this prepubertal advantage in growth tends to gradually decrease during puberty, when obese children show a reduced growth spurt compared with lean subjects. Growth hormone (GH) secretion in obese children is reduced, therefore suggesting that increased growth is GH independent. Factors which have been implicated in the accelerated growth in obese children include increased leptin and insulin levels, adrenal androgens, insulin- like growth factor (IGF)- 1, IGF- binding protein- 1 and GH- binding proteins. Excess body weight during childhood can also influence pubertal development, through an effect on timing of pubertal onset and levels of pubertal hormonal levels. There is clear evidence indicating that obesity leads to early appearance of pubertal signs in girls. In addition, obese girls are also at increased risk of hyperandrogenism. In boys, excess adiposity has been associated with advanced puberty in some studies, whereas others have reported a delay in pubertal onset. The existing evidence on the association between childhood and adolescence obesity underlines a further reason for fighting the epidemics of childhood obesity; that is preventing abnormal growth and pubertal patterns.

Pathophysiology and Management of Abnormal Growth in Children with Chronic Inflammatory Bowel Disease

Author(s): S. Ahmed, C. Farquharson, P. McGrogan, R.K. Russella

Many children with a variety of chronic diseases suffer from a variable component of chronic inflammation and often have co- existing growth retardation. The aetiology of this growth retardation may be multifactorial and in a condition such as inflammatory bowel disease it includes the effects of the disease on nutrition as well as the effect of drugs such as glucocorticoids. Growth is primarily regulated through the endocrine and paracrine component of the GH/IGF- 1 axis which may be modulated by other factors such as sex steroids. There is increasing evidence that this axis may be affected in children with chronic inflammation. An improved understanding of the GH/IGF- 1 axis and how it is affected in chronic inflammation will lead to an improved rationale for developing therapeutic regimens that can improve growth in those children whose growth does not improve despite optimal management of the disease. This review will illustrate these aspects by concentrating primarily on the pathophysiology of growth retardation in inflammatory bowel disease and possible interventions for improving growth.

Optimal Growth of Preterm Infants

Author(s): W. Corpeleijn, S. Kouwenhoven, J. van Goudoever

The cause of growth restriction in preterm infants is multifactorial, but it has been estimated that about 50% of the variance in early postnatal growth can be attributed to nutrition. Very low birth weight (VLBW) infants who were born small- for- gestational age (SGA) seem to have the highest risk to become growth restricted. Possibly, the intrauterine growth- retarded preterm infant is metabolically different from its appropriately grown counterpart and therefore has different nutritional needs. Neonatal nutrition and the resulting postnatal growth are major determinants in the short- and longterm outcomes of preterm neonates. Although having favorable effects on neurodevelopmental outcome, rapid postnatal weight gain after a period of nutritional restriction is associated with the development of insulin resistance and metabolic syndrome in later life. It seems likely that minimization of postnatal growth failure will decrease the need for catch- up growth and thereby decrease the risk of developing cardiovascular risk factors. Monitoring postnatal growth with current growth charts is complicated. Most growth charts that are currently being used are a reflection of current (nutritional) practices and are not a prescription of how VLBW should grow under optimal conditions. In addition to body weight, other aspects of growth such as lean body mass and length gain should also be taken into account when assessing the quality of postnatal growth. Noninvasive measurements of infant body composition are useful tools in evaluating the success of different nutritional interventions. However, all currently available methods have substantial drawbacks. A relatively new and promising method is air displacement plethysmography. This method still needs to be validated in preterm neonates. In conclusion, neonatal nutrition is a major determinant in the short- and long- term outcomes of preterm neonates. Monitoring postnatal growth is complicated by the lack of prescriptive growth charts and noninvasive measurements to assess the quality of growth.

Nutrition and Growth in Inflammatory Bowel Disease

Author(s): R. Shamir

Growth failure is common in children with inflammatory bowel disease (IBD), mainly those with Crohn’s disease (CD). The prevalence of growth failure varies in different cohorts, mainly due to the heterogeneity of the population treated by the reporting centers (primary vs. referral), but can be as high as 40% of the cases. Factors related to growth impairment in CD include low dietary intake, stool loss, increased energy and nutrient requirements, the use of medications (for example, steroids interfere with the IGF- 1 axis), disease activity (the effect of inflammation on growth), genetic background (parents height), and physical activity. In animals, malnutrition, genetic polymorphism, elevated pro inflammatory cytokines, and exposure to lipopolysaccharide are involved in growth impairment in IBD, while malnutrition, genetic polymorphism and increased inflammation have been shown to be associated with growth impairment in humans. Exclusive enteral nutrition (EEN) is the preferred first line treatment in CD. EEN induces remission, prolongs remission and affects growth failure via its effect on malnutrition and inflammation. However, similar to drug treatment, EEN effect on growth failure is limited, most probably due to incomplete control of inflammation. Children with IBD should be assessed for growth on diagnosis and on each follow- up visit. New nutritional strategies, identification of genetic polymorphisms that respond to EN, and methods to increase lean body mass (physical activity) are needed in order to improve growth in our IBD patients.

Early Growth and Later Atherosclerosis

Author(s): A. Singhal

The concept that early growth has long- term biological effects is based on extensive studies in animals dating from the 1930s. More recently, compelling evidence for a long- term influence of early growth on later health has also emerged in humans. Substantial data now support the hypothesis that ‘accelerated’, or too fast infant growth, increases the propensity to obesity, glucose intolerance, raised blood pressure, dyslipidaemia and endothelial dysfunction, the clustering of risk factors which predispose to the development of atherosclerotic cardiovascular disease (CVD). 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. These observations suggest, therefore, that the primary prevention of CVD should 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.

Body Composition in Young Children with Cystic Fibrosis

Author(s): J. Williams

Malnutrition in cystic fibrosis is an indication of poor prognosis and measurement of body composition may aid in identifying those at risk of poor clinical outcome. There is growing evidence of patients with cystic fibrosis having high fat and/or low fat- free mass which is likely to affect prognosis. Simple body composition techniques are based on assumptions about the nature of the fat- free mass and may therefore be biased; however, these techniques may be helpful in identifying children with high fat or low fat- free mass. The ‘gold standard’ 4- component model of body composition allows for more accurate assessment of fat mass and the components of fat- free mass.

Interaction between Weight and Medications in Psychological Illnesses of Children

Author(s): A. Apter, L. Steingart

Psychiatric medications have many implications on weight and growth. Stimulant medications may produce appetite loss and thus affect growth. Second- generation antipsychotics which are widely used for psychosis and many other indications may cause weight gain and subsequent metabolic disease. Weight loss such as that seen in anorexia nervosa may severely interfere with the efficacy of antidepressant agents.

Prematurity and Bone Health

Author(s): C. Pieltain, V. de Halleux, Th. Senterre, J. Rigo

Recent advances in neonatal care significantly increases survival rate in preterm and particularly inextremely low birth weight infants (ELBW infants) and nutrition is becoming one of the most challenging issue to improve short and long term health and developmental outcomes. Nutrition is also relevant for bone development and mineralization reducing the risk of osteopenia and metabolicbone disease (MBD). Osteopenia of prematurity is a multifactorial disease including predominantly nutritional but also biomechanical and environmental factors. At birth, the fetal active mineral transfer is interrupted and the preterm becomes related to the parenteral and enteral mineral supplies. On the other hand, physiological adaptation of bone to extra uterine life leads to an increase in bone resorption. This process occurring earlier in preterm than in term infants can be accompanied by an increased risk of bone fragility and fractures. Early provision of highly bioavailable mineral supplies, correction of vitamin D deficiency and the screening of serum phosphorus concentration combined to urinary mineral excretion appears to be helpful for the prevention of MBD. When available, DEXA is more sensitive than ultrasound for quantifying osteopenia in VLBW infants at the time of discharge. Catch-up of mineralization is rapidly observed during the post term period and osteopenia of prematurity seems to be a self-resolving disease although the potential long-term consequences on the attainment of peak bone mass remains uncertain.