Lower protein in infant formula is associated with lower weight up to age 2 y: A randomized clinical trial

Dr von Hauner Children's Hospital, University of Munich Medical Centre, Munich, Germany.
American Journal of Clinical Nutrition (Impact Factor: 6.77). 05/2009; 89(6):1836-45. DOI: 10.3945/ajcn.2008.27091
Source: PubMed

ABSTRACT Protein intake during infancy was associated with rapid early weight gain and later obesity in observational studies.
The objective was to test the hypothesis that higher protein intake in infancy leads to more rapid length and weight gain in the first 2 y of life.
In a multicenter European study, 1138 healthy, formula-fed infants were randomly assigned to receive cow milk-based infant and follow-on formula with lower (1.77 and 2.2 g protein/100 kcal, respectively) or higher (2.9 and 4.4 g protein/100 kcal, respectively) protein contents for the first year. For comparison, 619 exclusively breastfed children were also followed. Weight, length, weight-for-length, and BMI were determined at inclusion and at 3, 6, 12, and 24 mo of age. The primary endpoints were length and weight at 24 mo of age, expressed as length and weight-for-length z scores based on the 2006 World Health Organization growth standards.
Six hundred thirty-six children in the lower (n = 313) and higher (n = 323) protein formula groups and 298 children in the breastfed group were followed until 24 mo. Length was not different between randomized groups at any time. At 24 mo, the weight-for-length z score of infants in the lower protein formula group was 0.20 (0.06, 0.34) lower than that of the higher protein group and did not differ from that of the breastfed reference group.
A higher protein content of infant formula is associated with higher weight in the first 2 y of life but has no effect on length. Lower protein intake in infancy might diminish the later risk of overweight and obesity. This trial was registered at as NCT00338689.

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Available from: Jean-Paul Langhendries, Sep 27, 2015
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    • "Previous studies have evidenced perinatal nutrition environment as the risk factor for the development of metabolic disease in the adulthood of the offspring (Armitage et al., 2008). An epidemiological study revealed that children fed on milk formulas gained more weight, when compared with those fed on breast milk, with greater body mass index (BMI) at 24 months of age and increased risk of childhood overweight and obesity (Koletzko et al., 2009). Nutritional insults suffered in the early childhood periods may be related to the morphological and physiological changes in the adulthood, resulting in the phenomenon of phenotypic plasticity (Wells, 2007). "
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    ABSTRACT: This study evaluated the long-term effects of a westernized diet during pregnancy and lactation. Female Wistar rats (n = 12) were divided into two groups according to their food intake, namely, control (C) or westernized (W) diet, throughout pregnancy/lactation. On the 21st day, the male pups were weaned on a standard diet as follows: Control diet (CC) (n = 8) and westernized diet in perinatal life followed by control diet post weaning (WC) (n = 8). The levels of fasting (12 h) serum glucose, triglycerides (TG), and total cholesterol and fraction in the pups were determined. During weaning, the WC group showed 14% greater body weight (p < 0.001). In the adulthood, the offspring from dams fed on westernized diet showed hyperphagia, hyperinsulinism, hypertriglyceridemia, higher fat visceral weight, higher very-low-density-lipoprotein cholesterol level, decreased high-density-lipoprotein cholesterol level, and altered glucose tolerance test. In conclusion, maternal western-style diet in early life altered long-term food intake, visceral fat pad, insulin, glucose and lipid serum, and increased risk of metabolic disorders.
    International Journal of Food Sciences and Nutrition 09/2014; 65(8). DOI:10.3109/09637486.2014.950208 · 1.21 Impact Factor
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    • "Notably, increased postnatal catch-up growth in small for gestational age infants is associated with increased postnatal mTORC1 signalling and increased childhood asthma risk [22]. Moreover, excessive postnatal protein intake by formula feeding increases weight gain, total body fat mass and increases the risk of childhood obesity [23-25], which has been linked to increased amino acid-mediated mTORC1-signalling [26]. "
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    ABSTRACT: This article provides a new view of the cellular mechanisms that have been proposed to explain the links between infant formula feeding and the development of atopy and obesity. Epidemiological evidence points to an allergy- and obesity-preventive effect of breastfeeding. Both allergy and obesity development have been traced back to accelerated growth early in life. The nutrient-sensitive kinase mTORC1 is the master regulator of cell growth, which is predominantly activated by amino acids. In contrast to breastfeeding, artificial infant formula feeding bears the risk of uncontrolled excessive protein intake overactivating the infant's mTORC1 signalling pathways. Overactivated mTORC1 enhances S6K1-mediated adipocyte differentiation, but negatively regulates growth and differentiation of FoxP3(+) regulatory T-cells (Tregs), which are deficient in atopic individuals. Thus, the "early protein hypothesis" not only explains increased mTORC1-mediated infant growth but also the development of mTORC1-driven diseases such as allergy and obesity due to a postnatal deviation from the appropriate axis of mTORC1-driven metabolic and immunologic programming. Remarkably, intake of fresh unpasteurized cow's milk exhibits an allergy-preventive effect in farm children associated with increased FoxP3(+) Treg numbers. In contrast to unprocessed cow's milk, formula lacks bioactive immune-regulatory microRNAs, such as microRNA-155, which plays a major role in FoxP3 expression. Uncontrolled excessive protein supply by formula feeding associated with the absence of bioactive microRNAs and bifidobacteria in formula apparently in a synergistic way result in insufficient Treg maturation. Treg deficiency allows Th2-cell differentiation promoting the development of allergic diseases. Formula-induced mTORC1 overactivation is thus the critical mechanism that explains accelerated postnatal growth, allergy and obesity development on one aberrant pathway.
    Allergy Asthma and Clinical Immunology 07/2014; 10(1):37. DOI:10.1186/1710-1492-10-37 · 2.03 Impact Factor
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    • "and was conducted and nine trials in this age group were identified [27] [28] [29] [30] [31] [32] [33] [34] [35]. However none of them targeted energy intake from formula-milk, the focus of the baby milk intervention. "
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    ABSTRACT: . We describe our experience of using the Medical Research Council framework on complex interventions to guide the development and evaluation of an intervention to prevent obesity by modifying infant feeding behaviours. Methods . We reviewed the epidemiological evidence on early life risk factors for obesity and interventions to prevent obesity in this age group. The review suggested prevention of excess weight gain in bottle-fed babies and appropriate weaning as intervention targets; hence we undertook systematic reviews to further our understanding of these behaviours. We chose theory and behaviour change techniques that demonstrated evidence of effectiveness in altering dietary behaviours. We subsequently developed intervention materials and evaluation tools and conducted qualitative studies with mothers (intervention recipients) and healthcare professionals (intervention deliverers) to refine them. We developed a questionnaire to assess maternal attitudes and feeding practices to understand the mechanism of any intervention effects. Conclusions . In addition to informing development of our specific intervention and evaluation materials, use of the Medical Research Council framework has helped to build a generalisable evidence base for early life nutritional interventions. However, the process is resource intensive and prolonged, and this should be taken into account by public health research funders. This trial is registered with ISRTCN: 20814693 Baby Milk Trial.
    Journal of obesity 07/2014; 2014(9254):646504. DOI:10.1155/2014/646504
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