Abstract • 175

Perinatal infections are still a major problem in neonatal care. Preterm delivery is often associated with subclinical intramniotic infection and oxidative stress. Generation of reactive oxygen species (ROS) may be related to increased activation of immunoinflammatory cells by lytic enzymes, chemoattractants, pro-inflammatory cytochines, growth factors, vasoactive agents and ROS. Thus ROS generation appear to be a vicious circle in which ROS are both promoters and products. The formation of O2- is indeed the first step of the killing reaction; it is followed by production of other ROS namely H2O2, by superoxide dismutase, hydroxyl radical by a transition metal-catalyzed reaction, HOCl- by myeloperoxidase. Combination of highly reactive free radicals, in a biological environment may generate further unstable molecules, such as organic hydroperoxides and alkoxy radicals, which help to kill microorganisms and dispose of damaged tissue. Immunoinflammatory cells may stimulate endothelial production of humoral factors and adhesion molecules which in turn attract and activate neutrophils. These events presumably play a role in the pathogenesis of hypoxic-ischemic brain injury following microglial cell activation. Antiinflammatory interventions include efforts to modulate nitric-oxide activity, therapies directed at neutrophilic adhesion molecules, as well as administration of tissue-factor pathway inhibitors, activated protein C, albumin, chain-breaking antioxidants, ferriheme-bound drugs, natural cytokine antagonists and immunotherapy. A single solution seems improbable. Future approaches involve the clinical adaptation of molecular biological techniques such as gene therapy and antisense technology.