38 Chapter 2 showed that protein intake in the first weeks of life was positively correlated with the cognitive and motor score on the Bayley Scales of Infant Development (77, 78). In addition Biasini and colleagues found that increased protein intake in extremely low birth weight infants improved performance and hearing/language scores on the Griffith Development Mental Score at 3 and 12 months corrected age (79). Moreover increased fat free mass, which is claimed to reflect protein accretion, was associated with faster neuronal processing at 4 months corrected age (80). Also, perinatal protein restriction in mice altered the intracerebral dopamine circuit whichcausedaltered reward-processingandhyperactivity (81). The authors suggest that this could possibly be translated to adverse neurodevelopmental outcome, such as ADHD, in growth restricted infants. Furthermore in preterm infants who were fed a high nutrient diet larger caudate volumes and higher verbal IQ were found in adolescence (82). So far pathways explaining the associationbetweenneurodevelopment andprotein intake are still speculative. Compared to other nutrient components the unique feature of protein might just lie in the alteration of neuronal processing. Perhaps that the underlying mechanism works through increased neurotransmitter- and receptor synthesis. Indeed increased lactalbumin intake in rats increased cortex tryptophan. Nevertheless casein had a negative effect on tryptophan (83). Also de Kieviet and colleagues found an increased oral glutamine intake to be associated with increased white matter-, hippocampus-, and brain stem volumes in very preterm children at school age (84). Since glutamine has been shown to reduce the number of serious infections in very preterm children, they hypothesized that increased glutamine intake indirectly influences neurodevelopment by reducing infections in the neonatal period. IGF I and dietary proteins As stated earlier IGF I levels are related to nutritional intake. Socha et al. demonstrated that infants fed high-protein follow-up formula had higher IGF I levels than those fed low-protein follow-up formula (26). Moreover a minimal caloric as well as a minimal protein intake has to be reached to maintain normal IGF I levels (12). Furthermore there is a strong negative effect of breast milk on IGF I levels. Next to the lower protein content other, yet to be determined, factors might play a role in establishing this effect (85). Given the reciprocal relation between IGF I and nutrition, nutritional interventions might be the key factor in improving growth, body composition and neurodevelopmental outcome of preterm infants. Interestingly, Hansen-Pupp and colleagues found that IGF I and nutritional intake only correlated after a postmenstrual age of 30 weeks (14). The timing of a nutritional intervention may therefore be crucial for the sustainability of its effect.
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