71 IGF-I and nutrition in preterm infants 4 Introduction Preterm birth leads to an abrupt disruption of fetal development, leaving preterm infants in a precarious situation where they need to thrive despite an immature gastrointestinal tract and not fully developed immune and endocrine functions. Insulin-like growth factor 1 (IGF-1) stimulates growth and plays a crucial role in the complex association between early nutrient intake, growth, and maturation (1). In preterm infants, IGF-1 is mainly stimulated by insulin and nutrition (1, 2). However, to what extent various macronutrients impact IGF-1 levels in different phases of postnatal life is yet to be elucidated. In the fewstudies relatingactual nutrient intake to IGF-1 levels betweenpretermbirth and hospital discharge, protein and energy intake had a positive association with IGF-1 levels (3-5). Remarkably, one previous study reported that in preterm infants, the positive association between IGF-1 and nutrient intake was only apparent after 30 weeks postmenstrual age (PMA) (4). This suggests that there might be a limited window of opportunity for nutrition to influence early postnatal growth. It is to be noted that, to the best of our knowledge, only protein and energy intake have been studied in relation to IGF-1 levels in preterm infants. Interestingly, in adults, studies assessing fat and carbohydrate intake in relation to IGF-1 have been inconclusive. This leaves us with a gap in knowledge concerning the potential impact of dietary fat and carbohydrate intake on IGF-1 levels in preterm infants (6-8). In addition, the route of nutrient administration is another largely uncharted research area in relation to IGF-1 levels in preterm infants. Animal studies have shown that in a state of inflammation or poor nutrient intake, enteral feeding results in higher IGF-1 levels thanparenteral feeding. This is thought to be due to a reduction in inflammatory cytokine levels after enteral feeding (9, 10). These findings suggest that the route of nutrient administration could mediate cytokine production and consequently influence IGF-1 levels. Toour knowledge, this is yet tobe investigated inpreterminfants. Given the impact of poor growth and subsequent accelerated growth on later health outcomes in infants born preterm (11-13), it is pertinent to gain insight into factors influencing early postnatal growth, in order to obtain potential interventions to avert later adverse outcomes. In this light, the association between nutrition and IGF-1 is of particular interest, because nutrition is a factor which lends itself well for intervention and could lead to changes in clinical practice. Nevertheless, research on the relationship between nutrition and IGF-1 in preterm infants is scarce, andmost studies were published over a decade ago. Meanwhile, nutrition and neonatal intensive care have significantly changed. In addition, in previous studies, the infants were either on full enteral feeds or the relationship with the proportion of parenteral feeding was not taken into account. In this explorative observational study, associations between the macronutrient intake, the proportion of parenteral feeding, and IGF-1 were assessed in very and extremely preterm infants between birth and 36 weeks PMA.
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