NUTRITION IN RELATION TO THE ENDOCRINE REGULATION OF PRETERM GROWTH AND BODY COMPOSITION
Preterm birth disrupts a key phase of human development. This thesis focused on the postnatal modulation of growth and body composition in preterm infants. Furthermore, the influence of nutritional intake and the immature endocrine axis on health outcomes was investigated. Part I. IGF-I and nutrition in relation to growth, body composition and health outcomes in preterm infants Low IGF-I levels between preterm birth and term age were associated with impaired growth up to term age and possibly an unfavourable body composition at term equivalent age. IGF-I levels were also associated with nutritional intake: higher caloric and protein intake were associated with higher IGF-I levels from a gestational age from 30 weeks onwards. In particular between 30 and 33 weeks postmenstrual age, higher macronutrient and total caloric intake were associated with higher IGF-I levels. Furthermore, parenteral nutrition in the second week of life, which is the major source of nutrition at that time, was found to be associated with lower IGF-I levels. In addition, low IGF-I levels between preterm birth and 36 weeks postmenstrual age increased the odds of BPD. Furthermore, a higher intake of donor human milk increased the odds of BPD. Hence there may be a window of opportunity to increase IGF-I levels through nutritional interventions and thus improve growth, body composition and health outcomes in infants born preterm. Part II. Determinants and assessment of body composition in preterm infants There are concerns that infants born preterm have a less favourable body composition in infancy, i.e. lower fat free mass, compared to infants born at term. This in turn may be associated with adverse cardiometabolic outcomes in later life. Despite these concerns, there are no guidelines on which methods should be used to assess body composition in preterm infants. Nevertheless, it was demonstrated that commonly accepted methods show poor agreement. A systematic review of the literature, showed that there are actually very few studies validating commonly accepted methods to measure body composition in preterm infants against one another. In current practice, DXA, ADP and isotope dilution, are accepted as accurate measures. Nevertheless, there is variation within and between these methods and our systematic review showed that the statistical agreement between ADP and isotope dilution may be interpreted as poor. Therefore, caution should be taken when comparing body composition measured with different methods. To facilitate future studies and support clinical practice it would be valuable for researchers and physicians to come to an agreement on which reference should preferentially be used to measure body composition in preterm infants. In our studies, we primarily used ADP and suggest the use of ADP or DXA or isotope dilution depending on local availability and expertise. Monitoring body composition remains important in the light of the potential increased cardiometabolic disease risk in adults born prematurely. Early life events and possible interventions in this period may have the potential of improving long term outcomes of preterm infants. Indeed, it was shown that higher IGF-I levels in the first month of life are associated with increased fat free mass at term equivalent age. These findings suggest that the window of opportunity to improve the body composition of preterm infants may be limited to the early postnatal phase. In this phase interventions to increase IGF-I levels may have the potential to improve health outcomes of infants born preterm. Meanwhile after this phase IGF-I levels would have reached a threshold value where IGF-I determines the growth rate and further enrichment of nutrition could lead to an unfavourable body composition due to increased fat mass deposition.