175 General discussion 8 Even so, Leviton and colleagues reported positive associations between certain pro-inflammatory proteins and IGF-I. For example, vascular cell adhesion molecule 1, which mediates the adhesion of leukocytes to vascular endothelium, increases as IGF-I levels increase. Also, matrix metallopeptidase 9, a regulatory factor in neutrophil migration, is positively associated with IGF-I. (22) Hypothesizing IGF-I may have pro-inflammatory as well as anti-inflammatory properties, which has also been implied by older studies. (26) This warrants for further research. Especially, in the light of recent studies on the administration of IGF-I in preterm infants which failed to show a reduction in the occurrence of retinopathy of prematurity, but did find a significant reduction in the occurrence of bronchopulmonary dysplasia. (27) Speculatively, the balance between the pro- and anti-inflammatory properties of IGF-I may have played a role in this. Determinants and assessment of body composition in preterm infants Body composition in infancy and childhood is influenced by early life events. For example, disease severity after preterm birth is negatively associated with fat free mass in infancy. (28) Also nutrition and growth patterns in early life influence body composition. Both increased energy and protein intakes between preterm birth and hospital discharge have been shown to be associated with higher fat free mass at hospital discharge. (29) In line with these findings weight gain between preterm birth and term equivalent age has shown positive correlations with fat free mass at term equivalent age.(30, 31) After preterm birth, however, it is a challenge to administer the recommended amount of nutrients, resulting in relative malnutrition in the first week of life. Moreover, preterm birth is associated with potentially severe comorbidities, especially with decreasing gestational age at birth. Therefore unsurprisingly, postnatal growth restriction is often seen in preterm infants.(32) In line with the previously mentioned association between growth and lean mass, in the case of preterm infants who frequently suffer postnatal growth restriction, a relative increase in fat mass is expected to be seen. Indeed, increased fat mass at term equivalent age has been described when comparing preterm infants with those born at term and when comparing extremely preterm to very preterm infants. (33) Thus, body composition is a reflection of the condition of the infant in early life. It would be insightful to investigate the influence of optimizing IGF-I levels, either through dietary interventions or administration of IGF-I in the first weeks of life, on later body composition. To the best of our knowledge there are no reports on the effect of IGF-I administration on body composition in preterm infants or animal models resembling preterm infants. Interestingly in children with growth hormone insensitivity, higher doses of IGF-I administration, led to an increase in fat mass percentage. (34) Hypothesizing, there may be a doseresponse relationship in preterm infants as well, where a moderate IGF-I levels would stimulate lean mass, while higher levels would increase adiposity.
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