Growth during the earliest stages of life is an important determinant of an individual’s later health and risk of chronic disease. Substantial evidence shows that growth in the first 2 years of life, especially high early weight gain, is associated with adverse health outcomes later in life, including increased blood pressure, increased weight gain and body fat deposition and increased risk of diabetes. Higher protein intake for infants who are formula fed may play a role with these health outcomes because formula-fed children reach a higher body weight and weight for length at one year of age compared to those fed breast milk. A lower protein intake in infant formula is associated with lower weight up at 2 years of age which might be beneficial because the slower pattern of growth in breastfed infants might be protective for the development of the metabolic syndrome. In preterm infants, however, a higher protein intake in the first month of life correlates with improved neurodevelopment. Preterm infants have higher protein turnover rates and protein losses than terms and thereby higher protein requirements. Excessive intake of amino acids has been shown to reduce (brain) growth and to influence neurotransmitter concentrations in the brain of rats which might put the developing brain at risk. Inadequate amino acid intake impairs protein synthesis, which is pivotal for growth. The growth rate of the preterm infant should mimic at least the growth rate of the intrauterine fetus at the same gestational age. Achieving appropriate growth and nutrition accretion of preterm neonates is often difficult during hospitalization because of metabolic and gastrointestinal immaturity and other complicating medical conditions. Many preterm neonates require total parental nutrition for their initial nutritional support but this is associated with several complications, including the increased risk of infection, mucosal atrophy and cholestatic jaundice. Therefore, transition to full enteral feeding and the cessation of TPN are accomplished as soon as feasible and safe, taking in consideration that enteral feeding is associated with a detrimental morbidity like necrotising enterocolitis. Enteral nutrition can be initiated immediately after birth by introducing small amounts to enhance the development of the gastro-intestinal tract and for this reason is referred to as “trophic”, “priming” or “minimal enteral feeding”.

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The studies presented in this thesis were financially supported by Danone Research BV. The study formula was manufactured by SHS United Kingdom, and transportation to Shanghai was facilitated by Dumex China. The study sponsors had no influence on the study design, the analysis of the data or the writing of the manuscript.
J.B. van Goudoever (Hans)
Erasmus University Rotterdam
Erasmus MC: University Medical Center Rotterdam

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