OBJECTIVE: Free oxygen radicals and proinflammatory cytokines are important causes for brain injury in neonates with hypoxic ischemic encephalopathy (HIE). Our objectives were to test the hypothesis that a combination of antioxidants (ascorbic acid) and anti-inflammatory agents (ibuprofen) can ameliorate the brain injury in HIE and improve neurodevelopmental outcomes when given to term infants immediately after birth. STUDY DESIGN: In a prospective, randomized, double-blinded controlled trial, 60 asphyxiated term infants were assigned to one of two groups, intervention and control. The intervention group (n=30) received intravenous ascorbic acid and oral ibuprofen for 3 days; and the control group (n=30) received similar volumes of a placebo. We measured a panel of cytokines at enrollment and administered the treatment drugs within 2 h after birth. Neurological evaluations and developmental screenings were performed for all survivors at 6 months of age. RESULT: The Intervention and Control groups did not differ in the severity of HIE at enrollment, the concentrations of IL-1 beta and IL-6, the incidence of mortality (37 vs 33%), the incidence of neurological abnormalities at hospital discharge (47 vs 55%) and the incidence of developmental delay at 6 months of age (32 vs 40%), respectively. None of the observed complications were related to intervention. Serum interleukin (IL)-1beta and IL-6 concentrations correlated positively with the severity of HIE at birth (P<0.01), whereas only serum IL-6 correlated with neurodevelopmental outcome at 6 months (P<0.001). CONCLUSION: Early administration of ascorbic acid and ibuprofen did not affect outcomes in infants with perinatal asphyxia. This study does not explain whether our intervention was not effective in blocking free radicals and inflammatory cytokines, if the dosing and route of administration were inadequate, or if other mediators existed that could have a more powerful role in brain injury during hypoxia-ischemia.
RCT Entities:
OBJECTIVE:Free oxygen radicals and proinflammatory cytokines are important causes for brain injury in neonates with hypoxic ischemicencephalopathy (HIE). Our objectives were to test the hypothesis that a combination of antioxidants (ascorbic acid) and anti-inflammatory agents (ibuprofen) can ameliorate the brain injury in HIE and improve neurodevelopmental outcomes when given to term infants immediately after birth. STUDY DESIGN: In a prospective, randomized, double-blinded controlled trial, 60 asphyxiated term infants were assigned to one of two groups, intervention and control. The intervention group (n=30) received intravenous ascorbic acid and oral ibuprofen for 3 days; and the control group (n=30) received similar volumes of a placebo. We measured a panel of cytokines at enrollment and administered the treatment drugs within 2 h after birth. Neurological evaluations and developmental screenings were performed for all survivors at 6 months of age. RESULT: The Intervention and Control groups did not differ in the severity of HIE at enrollment, the concentrations of IL-1 beta and IL-6, the incidence of mortality (37 vs 33%), the incidence of neurological abnormalities at hospital discharge (47 vs 55%) and the incidence of developmental delay at 6 months of age (32 vs 40%), respectively. None of the observed complications were related to intervention. Serum interleukin (IL)-1 beta and IL-6 concentrations correlated positively with the severity of HIE at birth (P<0.01), whereas only serum IL-6 correlated with neurodevelopmental outcome at 6 months (P<0.001). CONCLUSION: Early administration of ascorbic acid and ibuprofen did not affect outcomes in infants with perinatal asphyxia. This study does not explain whether our intervention was not effective in blocking free radicals and inflammatory cytokines, if the dosing and route of administration were inadequate, or if other mediators existed that could have a more powerful role in brain injury during hypoxia-ischemia.
Authors: Nicola J Robertson; Sidhartha Tan; Floris Groenendaal; Frank van Bel; Sandra E Juul; Laura Bennet; Matthew Derrick; Stephen A Back; Raul Chavez Valdez; Frances Northington; Alistair Jan Gunn; Carina Mallard Journal: J Pediatr Date: 2012-02-09 Impact factor: 4.406
Authors: Alexis A Topjian; Robert A Berg; Joost J L M Bierens; Christine M Branche; Robert S Clark; Hans Friberg; Cornelia W E Hoedemaekers; Michael Holzer; Laurence M Katz; Johannes T A Knape; Patrick M Kochanek; Vinay Nadkarni; Johannes G van der Hoeven; David S Warner Journal: Neurocrit Care Date: 2012-12 Impact factor: 3.210
Authors: Alexander Trofimov; Tatyana Strekalova; Niall Mortimer; Olga Zubareva; Alexander Schwarz; Evgeniy Svirin; Aleksei Umriukhin; Andrei Svistunov; Klaus-Peter Lesch; Victor Klimenko Journal: Neurotox Res Date: 2017-04-18 Impact factor: 3.911
Authors: Michael S Wolf; Mioara D Manole; Lee Ann New; Yaming Chen; Elif Soysal; Patrick M Kochanek; Hülya Bayır; Robert S B Clark Journal: Pediatr Res Date: 2021-04-12 Impact factor: 3.953