Perinatal inflammation as major risk factor

Systemic inflammatory response system is a complex network of circulating mediators such as pro-inflammatory cytokines and changes in hemodynamics, the tissue perfusion and the coagulation-fibrinolysis system. Despite advances in postnatal surfactant replacement, drug-induced closure of the ductus arteriosus, more physiologic ventilation techniques, improved nutrition, and strategies to reduce higher-grade intraventricular hemorrhage the increased survival of very low birth weight infants has not been associated with a decrease in major neurodevelopmental impaiment. Obviously the activation of the systemic inflammatory response to the high prevalence of infection is a major determinant in the formation of neurological lesions. Recently a large prospective study in 6093 very low preterm infants (401–1000 gr, 80% of a surviving birth cohort) has demonstrated the pivotal role postnatal infection may have on the formation of neurodevelopmental deficits (Stoll BJ et al. JAMA, 292; 2357, 2004). The high prevalence of infections (65%) was associated with a high proportion of neurodevelopmental impairments at the age of 18 to 21 months (41%). Infants with infections had also higher rates of broncho-pulmonary dysplasia (52 vs. 27%), severe intraventricular hemorrhage (15 vs. 10%), and periventricular leukomalacia (3 vs. 8%). Only 29% of uninfected infants had developmental defects compared to 43% of infants with infections and 50% with sepsis. If we are able to reduce the inflammatory response and the consequences of infections, the proportion of preterm infants with neurodeveolpmental deficits can be reduced by up to 30%. Characterizing the inflammatory mechanisms and developing new treatment options (similar as in pulmonary inflammation following mechanical ventilation) is of paramount interest.