151 Low Levels of Cystein are Associated with Increased Proinflamma-Tory Activity, Arterial Hypotension and Severe Intraventricular Hemorrhage in Preterm Infants

Abstract

Background: Increased proinflammatory activity is associated with oxidative stress, hemodynamic impairment and tissue damage. Cystein is an essential amino acid in preterm infants and metabolized to glutathione which is one of the most important intracellular antioxidant systems. Plasma levels of isoprostane are considered a stable marker of oxidative stress. Aim: To evaluate if plasma levels of cystein and isoprostane at 6 h of age are associated with proinflammatory activity and with subsequent morbidity in preterm infants.Methods: A two year prospective cohort study including inborn infants delivered at < 32 +0 gestational weeks after antenatal informed consent and excluding infants with major anomalies. 74 infants were enrolled with a mean (SD) gestational age of 27.1 (1.9) weeks. Blood sampling for analysis of proinflammatory (TNFá, IL-1 â, IL-2, IL-6, IL-8, IL-12, IFN- ã) and modulatory (IL-4, IL-10) cytokines was performed from umbilical cord and at 6 h postnatal age. Plasma levels of cystein and isoprostane were determined at 6 h postnatal age. Continuous invasive measurement of arterial blood pressure (ABP) was digitally stored during the first 72 h. Ultrasound examinations of the brain were performed at day 1, 3 and 7, at 6 weeks and at term age.Results: Levels of cystein in plasma at 6 h of age were positively related to gestational age at birth (r=0.46, p=0.001). Increased levels of IFN-ã, TNFá, IL-1â, IL-6 and IL-12 at 6 h were associated with a decrease in level of cystein (r=−0.37, p=0.002; r= -0.25, p=0.04; r=−0.45, p=0.000; r=−0.29, p=0.02 and r=−0.28, p=0.02 respectively). Level of cystein at 6h was positively related to average of mean ABP (0– 6 h), r=0.38, p=0.004. Decreased levels of cystein at 6 h were associated with development of severe IVH (grade III + IV), OR (95 % CI) 0.93 (0.88– 0.97), p=0.000. All associations remained significant after adjustment for gestational age and gender. Levels of isoprostane at 6 h were neither associated with cytokine levels in umbilical cord nor with those at 6h of age.Conclusion: Increased proinflammatory activity, arterial hypotension and development of severe IVH are associated with low levels of cystein early after birth in preterm infants.