Nutrition Publication

NNIW65 - Importance of Growth for Health and Development

Editor(s): A. Lucas, M. Makrides, E. E. Ziegler. vol. 65

The focus of this book covers three session outcomes: 1st session provides an overview and focused on the association of early growth with obesity and cardiovascular outcomes. The 2nd session concentrated on the interrelationship between growth and neurodevelopment and the 3rd session considered the control and assessment of physical growth.

Related Articles

Subject Index

The focus of the book cover three sessions outcomes: 1st session provides an overview and focused on the association of early growth with obesity and cardiovascular outcomes. The 2nd session concentrated on the interrelationship between growth and neurodevelopment and the 3rd session considered the control and assessment of physical growth.

Concluding Remarks

Author(s): A. Lucas, M. Makrides, E.E. Ziegler

The focus of the book cover three sessions outcomes: 1st session provides an overview and focused on the association of early growth with obesity and cardiovascular outcomes. The 2nd session concentrated on the interrelationship between growth and neurodevelopment and the 3rd session considered the control and assessment of physical growth.

Growth and Later Health: A General Perspective

Author(s): A. Lucas

Whilst growth and its derangement in disease have been a long-standing focus in pediatrics, increasing evidence points to a further, fundamental role of early growth in the programming of later health. In studies on animals and humans, rapid early growth is associated with higher risk of obesity and cardiovascular disease, and in animals, senescence and life span – a concept encapsulated in the postnatal growth acceleration hypothesis. This hypothesis explains the benefits of breastfeeding to infants for reduced cardiovascular disease risk in terms of their slower early growth and the fetal origins hypothesis in terms of the adverse postnatal catch-up growth in infants born small. Early growth, notably prior to full term, also influences brain development and cognition – and emerging evidence suggests diverse, broader effects, for instance cancer and the onset of puberty. Understanding the mechanisms, triggers and windows for such effects is important, given the major public health implications, including potential new opportunities for primary prevention of adult disease.

Early Infancy as a Critical Period for Development of Obesity and Related Conditions

Author(s): M.W. Gillman

The current obesity epidemic has affected even the youngest children in our societies, including those in the first months of life. Animal experiments suggest that the early postnatal period may be critical to development of healthful energy homeostasis and thus prevention of obesity. In humans, observational studies and follow-up of randomized feeding trials show that rapid weight gain in the first half of infancy predicts later obesity and higher blood pressure. Despite the mounting consistency of results, several questions remain to be answered before clinical or public health implications are clear. These include the need for body composition data in infancy and data from the developing world to identify modifiable determinants of gain in adiposity in the early weeks of life, to mount interventions to modify these determinants, to examine tradeoffs of more vs. less rapid weight gain for different outcomes, and to incorporate any interventions that prove to be efficacious into clinical and public health practice in a cost-effective manner.

Leptin, Nutrition, and the Programming of Hypothalamic Feeding Circuits

Author(s): S.G. Bouret

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.

Early Growth and Ageing

Author(s): J.H. Chen, E.C. Cottrell, S.E. Ozanne

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.

Does Early Growth Affect Long-Term Risk Factors for Cardiovascular Disease?

Author(s): A. Singhal

The concept that early growth and nutrition have long-term biological effects isbased on extensive studies in animals dating from the 1930s. More recently, compellingevidence for a long-term influence, or programming effect, of growth has also emergedin humans. Substantial evidence now supports the hypothesis that ‘accelerated’ or toofast infant growth increases the propensity to the major components of the metabolicsyndrome (glucose intolerance, obesity, raised blood pressure and dyslipidemia), theclustering 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, experimentaldata from prospective randomized controlled trials strongly support a causal linkbetween infant growth and later cardiovascular risk factors. These observations suggesttherefore that the primary prevention of cardiovascular disease could begin fromas early as the first few months of life. The present review considers this evidence, theunderlying mechanisms involved and its implications for public health.

Developing World Perspective: The Importance of Growth for Short-Term Health

Author(s): L.S. Adair

Recently, concern has been raised about the potential adverse long-term consequences of rapid child growth. Rapid early childhood weight gain is associated with increased likelihood of being overweight or obese later in childhood and of having risk factors for the development of chronic disease such insulin resistance and elevated blood pressure. This has led to concerns about the wisdom of promoting catch-up growth in infants born small for gestational age or in children with poor growth after birth. In considering the costs and benefits of promoting catch-up growth, we must not lose sight of the immediate health threats to children in resource-poor environments in developing countries where child morbidity and mortality remain high. The literature on short-term consequences of growth is limited by its focus on attained size as an indicator of prior nutritional status, but generally shows that children with evidence of poor prior growth are at greater risk of morbidity and mortality from common infectious diseases, including lower respiratory infections and diarrhea. In these settings, failure to promote compensatory growth may have devastating short-term consequences.

Postnatal Growth and Development in the Preterm and Small for Gestational Age Infant

Author(s): R.J. Cooke

A clear relationship exists between undernutrition, poorer growth and poor development in term and preterm infants. However, preterm infants are at greater risk than term infants. Undernutrition is more common and ‘programmed’ growth rates are almost six times faster. Thus, even short periods of nutritional deprivation may have significant effects. Recent advances have led to an improvement in early growth but very low birthweight infants remain small for gestational age at hospital discharge. Studies suggest that a ‘window of opportunity’ exists after hospital discharge, in that better growth between discharge and 2–3 months corrected age is paralleled by better development, and poorer growth is associated with poorer development. However, interventions aimed at improving growth and development have yielded varying results. This may partly be related to differences in study design as well as the composition of the nutrient-enriched formulas. Irrespective, one point is concerning, i.e. infant boys appear to be at a developmental disadvantage when fed a term infant formula after discharge. A single study has also suggested that dietary intervention can improve brain growth in term and preterm infants with perinatal brain injury. However, concern has been expressed about rapid ‘catch-up’ growth in preterm infants and the development of insulin resistance and visceral adiposity. Data from our group do not support the idea of increased or altered adiposity in preterm infants fed a nutrientenriched formula after hospital discharge.

Interrelationship between Growth and Development in Low and Middle Income Countries

Author(s): R. Martorell, P. Nguyen

Early childhood growth failure is a significant public health problem in developingcountries. We examine relationships between low birthweight and stunting withchild development. Compared to children born with normal birthweight, low birthweightchildren have substantially poorer cognitive and schooling outcomes later inlife. Linear growth failure leading to stunting mostly occurs before age 2 years, withstunting in older children reflecting growth failure in early life. Many studies showthat stunting is associated with poor mental and motor development in infants andwith low scores in cognitive tests, increased frequency of behavioral problems andpoor school achievement in older children. Very few studies have assessed the relativeimportance for development of prenatal vs. postnatal growth failure and even fewerhave done so using appropriate statistical techniques. The limited evidence to datesuggests growth during the first 2 years of life is more important than growth at anyother time, including the prenatal period, for predicting later cognitive development,schooling and educational achievement. In conclusion, children in settings of povertywho experience growth failure prior to age 2 years have reduced potential to succeedin school and to be productive members of society.

Role of Long-Chain Polyunsaturated Fatty Acids in Neurodevelopment and Growth

Author(s): M. Makrides, L.G. Smithers, R.A. Gibson

There has been intense interest in the role of the n-3 long-chain polyunsaturatedfatty acid (LCPUFA) docosahexaenoic acid (DHA, 22:6n-3), in growth and developmentof infants. In 2009, there are at least twelve published randomized controlledtrials (RCT) assessing the effects of LCPUFA supplementation of infant formula forpreterm infants and seventeen RCTs involving formula-fed term infants. In addition,at least five RCTs have investigated the effect of DHA supplementation during pregnancyand/or lactation on infant and early child development. Collectively, the publishedliterature has demonstrated no harm of dietary LCPUFA for infants regardlessof whether they are born preterm or at term. However, developmental benefit is moreconsistently observed in infants born preterm. This may be explained by the fact thatDHA accretion to neural tissues peaks during the fetal brain growth spurt in the lasttrimester of pregnancy. Infants born preterm are denied the full gestation period toaccumulate DHA and are at risk of incomplete DHA accumulation. New research isfocused on the timing and dose of DHA supplementation needed to optimize developmentaloutcomes.

Growth and Development of the Brain and Impact on Cognitive Outcomes

Author(s): P.S. Hüppi

Understanding human brain development from the fetal life to adulthood is of great clinical importance as many neurological and neurobehavioral disorders have their origin in early structural and functional cerebral maturation. The developing brain is particularly prone to being affected by endogenous and exogenous events through the fetal and early postnatal life. The concept of ‘developmental plasticity or disruption of the developmental program’ summarizes these events. Increases in white matter, which speed up communication between brain cells, growing complexity of neuronal networks suggested by gray and white matter changes, and environmentally sensitive plasticity are all essential aspects in a child’s ability to mentalize and maintain the adaptive flexibility necessary for achieving high sociocognitive functioning. Advancement in neuroimaging has opened up new ways for examining the developing human brain in vivo, the study of the effects of early antenatal, perinatal and neonatal events on later structural and functional brain development resulting in developmental disabilities or developmental resilience. In this review, methods of quantitative assessment of human brain development, such as 3D-MRI with image segmentation, diffusion tensor imaging to assess connectivity and functional MRI to visualize brain function will be presented.

Benefits and Harms of Iron Supplementation in Iron-Deficient and Iron-Sufficient Children

Author(s): M. Domellöf

Due to high iron requirements, young children are at risk for iron deficiency anemia. Iron supplements are therefore often recommended, especially since iron deficiency anemia in children is associated with poor neurodevelopment. However, in contrast to most other nutrients, excess iron cannot be excreted by the human body and it has recently been suggested that excessive iron supplementation of young children may have adverse effects on growth, risk of infections, and even on cognitive development.Recent studies support that iron supplements are beneficial in iron-deficient children but there is a risk of adverse effects in those who are iron replete. In populations with a low prevalence of iron deficiency, general supplementation should therefore be avoided. Iron-fortified foods can still be generally recommended since they seem to be safer than medicinal iron supplements, but the level of iron fortification should be limited. General iron supplementation is recommended in areas with a high prevalence of iron deficiency, with the exception of malarious areas where a cautious supplementation approach needs to be adopted, based either on screening or a combination of iron supplements and infection control measures.More studies are urgently needed to better determine the risks and benefits of iron supplementation and iron-fortified foods given to iron-deficient and iron-sufficient children.

Effects of Selective Dropout on Infant Growth Standards

Author(s): S. Van Buuren

Exclusively breastfed (EBF) infants have higher weight gain during the first2 months, and lower thereafter. The explanation for this phenomenon is not clear.Longitudinal data from the Social Medical Survey of Children Attending Child HealthClinics study with a cohort of 2,151 Dutch children were analyzed according to a patternmixture model. It appears that higher than average growth of EBF infants duringthe first 2 months is primarily attributable to selective dropout. Furthermore, betweenmonths 2 and 6, light nonEBF infants gain more weight than light EBF infants. Bothfactors aid in explaining differences in growth between EBF and nonEBF infants. TheWHO Child Growth Standards for weight-for-age have been calculated from a subgroupof 903 infants (out of 1,743) that complied with strict feeding criteria. If similardropout mechanisms operate in the Multicentre Growth Reference Study, then theWHO weight-for-age standards are expected to be systematically different from thosefor the entire group of 1,743 infants.

The 2000 Centers for Disease Control and Prevention Growth Charts: Several Insights after 8 Years

Author(s): C.L. Ogden, R. Wei, L.R. Curtin, K.M. Flegal

This paper explores three issues related to the 2000 Centers for Disease Control andPrevention growth charts. First, it clarifies the methods that were used to create thecharts as it has become apparent that the smoothing techniques have been somewhatmisunderstood. The techniques included smoothing-selected percentiles betweenand including the 3rd and 97th percentiles and then approximating these smoothedcurves using a procedure to provide the transformation parameters, lambda, mu, andsigma. Only the selected percentiles were used in this process due to small samplesizes beyond these percentiles. Second, given the concern that the infant charts werecreated with relatively few data points in the first few months of life, it compares theoriginal observed percentiles with percentiles that include newly available US nationaldata for the first few months of life. Third, it discusses the issues that arise if a 99thpercentile is extrapolated based on the lambda, mu, and sigma parameters. The 99thpercentile of the body mass index-for-age chart has been recommended to identifyextremely obese children, yet the 97th percentile is the highest available percentile onthe Centers for Disease Control and Prevention growth charts.

Growth Charts Compared

Author(s): E.E. Ziegler, S.E. Nelson

Growth assessment of children requires comparison of growth measurements withnormative references, usually in the form of growth charts. Traditionally growth charts(growth references) have described the growth of children who were considered normaland were living in a defined geographic area. The new WHO growth charts, on theother hand, are growth standards that aim to represent growth as it occurs worldwide.Moreover, they represent growth as it occurs under optimal circumstances and isthought to be conducive to optimal long-term health. Most growth references are single-country references, exemplified here by charts from the UK, the Netherlands andthe USA. By contrast, the Euro-Growth reference and the WHO standard are based onmultinational samples. Comparison of these five charts reveals surprisingly large differencesthat are for the most part unexplained. Differences between the WHO chartsand other charts are only partially explained by the use of a prescriptive approach andby the data truncation employed. The large differences between charts probably areof 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 thedifferences, however, is substantial.

Body Composition in Infancy: Impact on Health Later in Life

Author(s): K.J. Ellis

From retrospective studies, there is substantial evidence that birthweight and the rate of weight gain during early infancy are associated with increased risk for adverse health outcomes later in life. Birthweight is the marker of the integrative effects of the prenatal environment, while the rate of weight gain after birth reflects both genetic potential and external postnatal influences. The adulthood-to-infancy associations constitute the basis for the ‘fetal origins’ and ‘catch-up growth’ hypotheses for some diseases. However, these findings are based on the assumption that anthropometricbased indices reflect body composition during both time periods, with the body mass index (weight/stature2) being the most frequently used index. More direct measures of body composition were simply not available at the time of the births of the adults participating in these studies. Nowadays, there are a number of in vivo techniques that can be used to examine body composition in infancy. In particular, what does the body mass index reflect in terms of body composition for the infant? Is it an adequate index?

Endocrinology of Growth

Author(s): R.G. Rosenfeld

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.