35 Dietary proteins and IGF I levels in preterm infants 2 Inanalogywith thedevelopment of retinopathyof prematurity the suddendecrease in IGF I at birth could cause stagnation in vascular growth. It is hypothesized that the surge in IGF I might lead to neovascularisation with abnormal vessel formation, which could cause intracranial haemorrhage and consequently influence neurodevelopmental outcome. In experimental studies it has been suggested that IGF I may limit damage after hypoxic-ischemic brain injury and inflammation (47, 48). Moreover mice treated with IGF I seemed to have increased proliferation of immature oligodendrocytes, while the number of mature oligodendrocytes remained the same. This was hypothesized to possibly promote myelination at later stages when the immature oligodendrocytes mature and start myelinating (49). In addition lipopolysaccharide induced brain inflammation in a mouse model led to lower IGF I levels and impaired myelination in the subcortical white matter (50). However in a rat periventricular leukomalacia model it was demonstrated that exogenous IGF I limited lipopolysaccharide induced damage at a low dose, while it increased damage at higher doses (51). Recently IGF I administration has been investigated in a phase I study in preterm infants and showed to effectively increase IGF I levels without any adverse events (52). In the near future this might offer a therapeutic intervention potentially improving neurodevelopment as well as growth and body composition. The role of dietary proteins in growth and body composition In the first weeks of life preterm infants almost universally accumulate a protein deficit and show postnatal growth restriction. In an attempt to achieve an intrauterine-like growth rate neonatologists are challenged to administer the right composition of amino acids and the optimal amount of proteins, combined with sufficient fatty acids and carbohydrates, to optimize nitrogen accretion. Currently the recommended range of protein intake for preterm infants is 3.5 to 4.5 g/kg/day (53). Over the past few years increasing amounts of parenteral amino acids have been administered to preterm infants showing a consistent increase in protein balance. Recent nutritional studies have actually demonstrated that by administering high dose parenteral amino acids current recommendations for protein intake and intrauterine-like growth rates can be achieved, nutritional deficits can drastically be reduced and postnatal growth restriction can in part be prevented (Figure 2) (11). It is recognized that high and early introduction of proteins can limit the initial postnatal weight loss (54). By reducing initial weight loss the tendency for rapid ‘catch-up’ growth might be reduced, which may lead to more favourable metabolic programming. Indeed low protein levels are associated with low IGF I levels (55), which in turn is associated with fat mass accretion in childhood (35).
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