Therapeutic hypothermia in asphyxiated newborns: selective head cooling vs. whole body cooling — comparison of short term outcomes

Objectives: Therapeutic hypothermia TH became broadly used in the management of the asphyxiated newborns. Although two cooling methods are used, so far the superiority of none of them has been established. The purpose of the study is to compare two cooling methods: selective head cooling (SHC) and whole body cooling (WBC) Material and methods: We conducted a prospective observational study in newborns with HIE. The patients received one of methods: SHC or WBC. The eligibility criteria were similar to previous studies. Stability of cardio-respiratory parameters and short term outcomes were analyzed. Results: 78 neonates with hypoxic-ischemic encephalopathy due to perinatal asphyxia were involved in this study. The SHC group consisted of 51 newborns, the WBC group consisted of 27 patients. Both study groups had similar baseline characteristics and condition at birth. There were no significant differences in hospital course, neurological status and adverse effects associated with cooling procedure between groups. Analyzing the rate of thrombocytopenia and the number of transfusions of blood components no statistically significant differences were found between the groups. Conclusions: Results of our study indicate that two compared methods of TH despite varied target core temperature ranges do not differ significantly according to clinical course and risk of adverse events. Further observations are conducted and we look forward to the results of the long neurodevelopmental care

Effect of allopurinol in addition to hypothermia treatment in neonates for hypoxic-ischemic brain injury on neurocognitive outcome (ALBINO): Study protocol of a blinded randomized placebo-controlled parallel group multicenter trial for superiority (phase III)

Background: Perinatal asphyxia and resulting hypoxic-ischemic encephalopathy is a major cause of death and long-term disability in term born neonates. Up to 20,000 infants each year are affected by HIE in Europe and even more in regions with lower level of perinatal care. The only established therapy to improve outcome in these infants is therapeutic hypothermia. Allopurinol is a xanthine oxidase inhibitor that reduces the production of oxygen radicals as superoxide, which contributes to secondary energy failure and apoptosis in neurons and glial cells after reperfusion of hypoxic brain tissue and may further improve outcome if administered in addition to therapeutic hypothermia. Methods: This study on the effects of ALlopurinol in addition to hypothermia treatment for hypoxic-ischemic Brain Injury on Neurocognitive Outcome (ALBINO), is a European double-blinded randomized placebo-controlled parallel group multicenter trial (Phase III) to evaluate the effect of postnatal allopurinol administered in addition to standard of care (including therapeutic hypothermia if indicated) on the incidence of death and severe neurodevelopmental impairment at 24 months of age in newborns with perinatal hypoxic-ischemic insult and signs of potentially evolving encephalopathy. Allopurinol or placebo will be given in addition to therapeutic hypothermia (where indicated) to infants with a gestational age ≥ 36 weeks and a birth weight ≥ 2500 g, with severe perinatal asphyxia and potentially evolving encephalopathy. The primary endpoint of this study will be death or severe neurodevelopmental impairment versus survival without severe neurodevelopmental impairment at the age of two years. Effects on brain injury by magnetic resonance imaging and cerebral ultrasound, electric brain activity, concentrations of peroxidation products and S100B, will also be studied along with effects on heart function and pharmacokinetics of allopurinol after iv-infusion. Discussion: This trial will provide data to assess the efficacy and safety of early postnatal allopurinol in term infants with evolving hypoxic-ischemic encephalopathy. If proven efficacious and safe, allopurinol could become part of a neuroprotective pharmacological treatment strategy in addition to therapeutic hypothermia in children with perinatal asphyxia. Trial registration: NCT03162653, www.ClinicalTrials.gov, May 22, 2017