57 Bronchopulmonary dysplasia, IGF-I & nutrition 3 and endothelial lung injury 3 22. IGF-I is known to have a protective effect on inflammation and to show anti-oxidative effects, protecting cells from oxidativestress induced apoptosis 6-8. The protective effect on inflammation and the antioxidative effects of IGF-I may be important in decreasing the risk to develop BPD. In support of this, a recent study aiming to reduce the occurrence of retinopathy of prematurity by administering human recombinant IGF-I, showed that an increase in pro-inflammatory cytokines, e.g. Interleukin-6, is associated with a subsequent decrease in IGF-1 and IGF-I administration reduces the occurrence of BPD. 9 23 Possible interactions between nutrition, IGF-I levels and the occurrence of BPD In line with others, in our study, infants with BPD had a comparable macronutrient intake to infants without BPD. 16 Milanesi and colleagues recently reported that infants who developed BPD received less than the recommended daily protein/ energy ratio. 24 Nevertheless in our population infants reached the recommend daily intake by the second week of life. However, our study did show that infants who were predominantly fed donor human milk for at least a week had a higher odds of BPD compared to those who were predominantly fed donor human milk for a shorter period. Hypothetically, this could be due to the lower energy and macronutrient content of donor human milk compared to own mother’s milk. Yet, in our study population nutrient intake did not alter the association between donor human milk intake and the occurrence of BPD. (see web appendices) On the other hand, it has been described that human milk contains IGF-I and human milk IGF-I levels have been associated with growth in term infants. 25 Furthermore, Holder pasteurization can reduce IGF-I levels up to 40%. 26 Therefore, it could be hypothesized that donor human milk could lead to lower IGF-I levels in preterm infants. In addition to a possible direct uptake of IGF-I from human milk, it has been described that micronutrients and branched amino acids in human milk may stimulate the infant’s IGF-I axis. 27 Pasteurization also has been reported to affect these factors 28 and thus supports a potential negative effect of pasteurized donor humanmilk on endogenous IGF-I levels. In the future novel techniques such as High-Temperature-Short-Time pasteurization, high pressure processing and ultraviolet-C irradiation may offer alternatives to Holder pasteurization. 29 However, in our study participants were mainly fed own mother’s milk. (figure 3) The absolute quantity of donor human milk was small and did not correlate with the occurrence of BPD. Therefore, our findings remain speculative. Strengths and limitations Data on actual nutrient intake, as opposed to the prescribed amount, was collected prospectively and changes in IGF-I over time were calculated for every participant. Nevertheless, blood samples were taken every other week leading to a relatively low sample size in the analyses per week PMA.
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