85 IGF-I and nutrition in preterm infants 4 (3-5). However, Ëngstrom and colleagues found that in infants with a weight of less than 2000 g, protein supplementation had a stronger association with IGF-1 levels compared to infants over 2000 g. Perhaps this can explain why the positive trend our study found at 34 and 35 weeks PMA was not statistically significant. In contrast to the relationship between nutrient intake and concurrent IGF-1 levels describedabove, our results showednutrient intaketo influencethechange in IGF-1 at a younger PMA. For every macronutrient, intake from 28 weeks PMA was associated with the change in IGF-1 levels between birth and 32 weeks PMA. Hypothesizing, total macronutrient intake before 30 weeks may not reach the threshold to increase concurrent IGF-1 levels, but it might stimulate the IGF-1 axis to mature more rapidly and in this way cause a more rapid increase in IGF-1 levels over time. Strengths and Limitations This is the first study to evaluate the contribution of all macronutrients in relation to circulatory IGF-1 levels in preterm infants from birth until 36 weeks of gestation. In addition, to the best of our knowledge, the proportion of parenteral nutrition has not been investigated previously in relation to IGF-1 levels. In line with previous research, our results demonstrate a slow increase in IGF-1 levels in the first weeks of life (4). However, our results failed to support previous findings on nutrient intake per kg body weight. As previously mentioned, our population had little variation in nutrient intake per kg body weight. This could potentially explain the lack of statistically significant findings. In addition, despite the considerable overall sample size, this study had a relatively small sample size per week. This was due to the low sample frequency (on alternating weeks) and the relatively small number of extremely preterm infants, which resulted in a sample size ranging from 1 infant at 26 weeks PMA to 33 infants at 33 weeks PMA. This may have contributed to our findings. Moreover, it is important to note that this was an exploratory observational study. Therefore, the findings should be interpreted with caution and strong conclusions on potential causative relationships cannot be made. Conclusions Our findings further illustrate the complex association of maturation, concurrent comorbidities, and nutrition in relation to IGF-1 levels. The proportion of parenteral nutrition was found to be a negative predictor of IGF-1 levels, affirming the importance of stimulating enteral nutrition and limiting parenteral nutrition as much as possible in clinical practice. Our findings point towards a potential time frame inwhich nutrition is unable to impact IGF-1 levels. Future research should aim to narrow down this time frame and to gain more insight into factors enhancing or decreasing the response of IGF-1 to nutrition, e.g., age and inflammatory state, to align nutritional interventions accordingly.
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