Protein and energy requirements in infancy and childhood

Abstract

Some 30 years ago, Günter Dörner stated that the concentrations of hormones, metabolites and neurotransmitters during critical periods of early development will program disease risk in human adulthood, a concept that since has received enormous scientific support and broad attention. Evidence has also accumulated showing that early nutrition programs later obesity risk. Breastfeeding reduces the odds ratio for obesity at school age by about 20%, relative to formula feeding, adjusted for biological and sociodemographic confounding variables. We propose that the protective effect of breastfeeding is explained at least in part by the induction of lower rates of infant weight gain, which may be related to differences in substrate intakes with breast milk and standard infant formulae. Protein intake per kilogram body weight is some 55–80% higher in formula-fed than in breast-fed infants. We hypothesize that high early protein intakes in excess of metabolic requirements may enhance weight gain in infancy and later obesity risk (the ‘early protein hypothesis’). The European Childhood Obesity Project is testing this hypothesis in a randomized double-blind intervention trial in more than 1,000 infants in 5 European countries. Infants that are not breast fed are randomized to formulae with higher or lower protein contents and are followed up to school age. If an effect of infant feeding habits on later obesity risk should be established, there is great potential for effective preventive intervention with a significant potential health benefit for the child and adult population. Copyright © 2006 Nestec Ltd., Vevey/S. Karger AG, Basel Evidence is accumulating to show that metabolic events during critical time windows of preand postnatal development have marked modulating effects on health in later life, a concept often referred to as ‘programming’ or ‘metabolic programming’ [1]. It has been some three decades since Prof. Günter Dörner, 1 Requirements for Protein and Energy Rigo J, Ziegler EE (eds): Protein and Energy Requirements in Infancy and Childhood. Nestlé Nutr Workshop Ser Pediatr Program, vol 58, pp 1–18, Nestec Ltd., Vevey/S. Karger AG, Basel, © 2006. then head of the Institute of Experimental Endocrinology at the Charité Hospital, Humboldt University at Berlin, Germany, first introduced the term ‘programming’ into the scientific literature to describe these phenomena [2]. In a visionary article reviewing a series of clinical and experimental data, Dörner [3] concluded that the concentrations of hormones, metabolites and neurotransmitters during critical early periods of development are capable of preprogramming brain development and, up to human adulthood, functional disturbances, diseases as well as syndromes of reproduction and metabolism. Dörner also proposed an interaction between the genetic material of the individual and environmental influences during early development to determine later function in adult life, a concept that has only recently been confirmed by experimental data [1, 4–6]. The concept has gained wide popularity following epidemiological studies documenting inverse relationships between body weight at birth and at age 1 year, respectively, and the risks of hypertension, diabetes and coronary heart disease in adulthood [7]. These observations have led to the hypothesis that maternal malnutrition during pregnancy would induce both fetal growth restriction and increased later disease risk, the fetal origins of the adult disease hypothesis [7]. However, this interpretation has recently been challenged based on the observation that low birth weight is associated with catch-up growth after birth, and accelerated weight gain by itself seems to be a risk factor for later disease [8]. Cole [9] substantiated the latter concept by multiple regression analysis of blood pressure outcomes on weights at different ages. Data from cohort studies in Brazil and the Philippines relating blood pressure in adolescence to weight through childhood showed small inverse weight effects in infancy, but early weight proved to be less important than weight and weight gain during adolescence [9]. Furthermore, Tu et al. [10] raised the possibility that evidence for the fetal origins of adult disease hypothesis might be a statistical artifact known as the ‘reversal paradox’, due in part to inappropriate statistical adjustment for variables on the causal pathway such as early weight gain and current body size. They performed computer simulations for three hypothetical relations between birth weight and adult blood pressure. The effect of statistically adjusting for different correlations between current weight and birth weight and between current weight and adult blood pressure was examined to assess their impact on associations between birth weight and blood pressure. When there was no genuine relation between birth weight and blood pressure, adjustment for current weight created an inverse association the size of which depended on the magnitude of the positive correlations between current weight and birth weight and between current weight and blood pressure. When there was a genuine inverse relation between birth weight and blood pressure, the association was exaggerated following adjustment for current weight, whereas a positive relation between birth weight and blood pressure could be reversed after adjusting for current weight. Koletzko