Inflammation and the Insulin-like Growth Factor System at Very Preterm Birth. Implications for Early Morbidity and Development

Abstract: The intention of this thesis was to evaluate the effects of inflammation at very preterm birth on subsequent morbidity, as well as on the neuro-protective IGF-system. Prospective clinical studies of very preterm infants constituted a base for the evaluation. Temporal changes in levels of cytokines were chosen as markers of an induced inflammatory response and were evaluated together with components of the IGF-system at birth and during the first 3 postnatal days. The studies could describe associations between increased levels of pro-inflammatory cytokines and subsequent morbidity. Inflammation present in cord blood related to impaired developmental outcome at 2 years of age, as well as to changes in components of the IGF-system, which indicates that inflammation present already before delivery may injure the immature brain and interfere with neuro-protective mechanisms. A postnatal increase in cytokines was on the other hand associated with early morbidity, such as arterial hypotension and cerebral hemorrhage. Concentrations of IGF-I displayed a temporal decrease from birth and onwards, suggesting a low endogenous production after very preterm birth. We could show that exogenous administration of IGF-I from adult donor plasma elevated low endogenous levels of IGF-I in extremely preterm infants without any side effects. In summary, these findings imply that the time point of an induced inflammatory response appears important for type of subsequent morbidity. This may be of relevance for determining an optimal time point of delivery and for intervention with anti-inflammatory or protective strategies, with the purpose to decrease brain injury after very preterm birth.