Relationship between Isoprostane Concentrations, Metabolic Acidosis, and Morbid Neonatal Outcome

Abstract

When a fetus is subjected to a massive perinatal hypoxic-ischemic insult, it may suffer sufficient damage to cause intrauterine death and stillbirth (1)(2)(3)(4)(5). In less severe, nonfatal cases, prolonged or severe intrauterine hypoxia may lead to serious neonatal complications such as hypoxic-ischemic encephalopathy (HIE), cerebral palsy, and impaired myocardial function (6)(7)(8). Hypoxia during labor leads to anaerobic respiration in the fetus and an accumulation of lactic acid in the tissues, producing metabolic acidosis. Damage to the brain and heart in asphyxia neonatorum is not a direct result of hypoxia, but rather of the toxic effects of reactive oxygen species generated after reperfusion of ischemic tissues. We have demonstrated that lipid peroxidation in the fetus increases during normal labor (9) and that umbilical cord plasma lipid peroxide concentrations are higher in situations known to lead to intrapartum hypoxia (10)(11)(12) and much lower after elective cesarean delivery (13). Reperfusion of damaged organs with oxygenated blood after delivery may also be detrimental to the infant’s long-term survival. Prediction of long-term neurodevelopmental outcomes in infants with birth asphyxia remains challenging. Unfortunately, previous studies have shown that clinical and biochemical variables, such as umbilical artery blood gases or Apgar scores, are of limited value in predicting morbid neonatal outcome. We have proposed the use of lipid peroxidation products, acting as footprints of oxidative stress, as alternative measures of perinatal outcome (14). Increased concentrations of lipid peroxidation products in cord arterial blood are associated with clinical situations known to cause fetal distress, but they have not been shown to be associated with significant morbid outcomes such as HIE. This study aims to demonstrate an association between increased umbilical cord blood lipid peroxide concentrations and morbid neonatal outcomes. The study hypotheses …