83 IGF-I and nutrition in preterm infants 4 Discussion This study shows that the proportion of parenteral nutrition is negatively associated with IGF-1 levels in extremely and very preterm infants. Gestational age, BPD, and weight were significant confounders in the association between nutrient intake and IGF-1 levels. Total protein, fat, and carbohydrate intake, as well as total energy intake, showed a positive association with IGF-1 levels, particularly between 30 and 33 weeks PMA. The Effect of the Various Macronutrients on IGF-1 Levels Studies in preterm infants consistently show that protein intake is positively associated with IGF-1 levels (3-5). However, not all studies could show that energy intake was a predictor of IGF-1 after correction for confounders (3). In our study, higher total protein intake and higher total energy intake were associated with higher IGF-1 levels. In contrast to previous studies, our study did not find an association between nutrient intake per kg bodyweight and IGF-1 levels. Weight explained more of the variance in IGF-1 than nutrient intake. However, it should be noted that the variance in nutrient intake per kg bodyweight may have been too small to show significant differences in IGF-1 levels in our population. This is due to the univocal application of our local nutrition protocol. For example, from 33 weeks PMA the interquartile range in protein intake was between 3.7 and 4.1 g kg−1 day−1. This range was notably smaller compared to previous research (4) and could have limited the statistical power. To our knowledge, the impact of fat and carbohydrate intake on IGF-1 levels in preterm infants has not been studied previously. Meanwhile, studies in adults have been inconclusive, with some finding positive associations (7), while others found negative associations (6) or no association at all (8). In our study, total fat and total carbohydrate intake showed a positive association with IGF-1 levels. Interestingly, both carbohydrate and fat intake had a comparable impact on IGF-1 when compared to protein intake—a one SD change in any of the macronutrients led to a change of 0.6 SD in IGF-1 levels at 30 weeks PMA. Although it has been suggested that the role of proteins is more important than that of carbohydrates and fat in stimulating IGF-1 (3, 6), like dietary proteins, dietary fat and carbohydrates have been found to increase hepatic IGF-1 expression in animal studies (23). Moreover, fat and carbohydrates provide the majority of the total energy intake, which has repeatedly been shown to have a positive association with IGF-1 levels and thus supports our findings. The Route of Nutrient Administration Parenteral feeding was found to be negatively associated with IGF-1 levels. It could be hypothesized that less exposure of the gastrointestinal tract to nutrition enhances a pro-inflammatory state in the immature gut, which in turn could lead
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