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Objective: Therapeutic hypothermia (HT) is the standard treatment for newborns after perinatal asphyxia. Preclinical studies report that HT is more effective when started early. Methods: Eighty cooled newborns were analyzed and grouped according to when cooling was started after birth: early (≤180 min) or late (>181 min). For survivors we analyzed whether starting cooling early was associated with a better psychomotor or mental developmental index (PDI or MDI, Bayley Scales of Infant Development II) than late cooling. Results: Forty-three newborns started cooling early and 37 started late. There was no significant difference in the severity markers of perinatal asphyxia between the groups; however, nonsurvivors (n = 15) suffered more severe asphyxia and had significantly lower centiles for weight (BWC; p = 0.009). Of the 65 infants that survived, 35 were cooled early and 30 were cooled late. There was no difference in time to start cooling between those who survived and those who did not. For survivors, median PDI (IQR) was significantly higher when cooled early [90 (77-99)] compared to being cooled later [78 (70-90); p = 0.033]. There was no increase in cardiovascular adverse effects in those cooled early. There was no significant difference in MDI between early and late cooling [93 (77-103) vs. 89 (76-106), p = 0.594]. Conclusion: Starting cooling before 3 h of age in surviving asphyxiated newborns is safe and significantly improves motor outcome. Cooling should be initiated as soon as possible after birth in eligible infants.
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- Perlman JM, Wyllie J, Kattwinkel J, Atkins DL, Chameides L, Goldsmith JP, Guinsburg R, Hazinski MF, Morley C, Richmond S, Simon WM, Singhal N, Szyld E, Tamura M, Velaphi S: Neonatal resuscitation: 2010 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science with Treatment Recommendations. Pediatrics 2010;126:e1319-e1344.
- Edwards AD, Brocklehurst P, Gunn AJ, Halliday H, Juszczak E, Levene M, Strohm B, Thoresen M, Whitelaw A, Azzopardi D: Neurological outcomes at 18 months of age after moderate hypothermia for perinatal hypoxic ischaemic encephalopathy: synthesis and meta-analysis of trial data. BMJ 2010;340:c363.
- Jacobs SE, Berg M, Hunt R, Tarnow-Mordi WO, Inder TE, Davis PG: Cooling for newborns with hypoxic ischaemic encephalopathy. Cochrane Database Syst Rev 2013;1:CD003311.
- Gunn AJ, Gunn TR, Gunning MI, Williams CE, Gluckman PD: Neuroprotection with prolonged head cooling started before postischemic seizures in fetal sheep. Pediatrics 1998;102:1098-1106.
- Sabir H, Scull-Brown E, Liu X, Thoresen M: Immediate hypothermia is not neuroprotective after severe hypoxia-ischemia and is deleterious when delayed by 12 hours in neonatal rats. Stroke 2012;43:3364-3370.
- Jacobs S, Hunt R, Tarnow-Mordi W, Inder T, Davis P: Cooling for newborns with hypoxic ischaemic encephalopathy. Cochrane Database Syst Rev 2007;4:CD003311.
- Gluckman PD, Wyatt JS, Azzopardi D, Ballard R, Edwards AD, Ferriero DM, Polin RA, Robertson CM, Thoresen M, Whitelaw A, Gunn AJ: Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trial. Lancet 2005;365:663-670.
- Shankaran S, Laptook AR, Ehrenkranz RA, Tyson JE, McDonald SA, Donovan EF, Fanaroff AA, Poole WK, Wright LL, Higgins RD, Finer NN, Carlo WA, Duara S, Oh W, Cotten CM, Stevenson DK, Stoll BJ, Lemons JA, Guillet R, Jobe AH: Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N Engl J Med 2005;353:1574-1584.
- Simbruner G, Mittal RA, Rohlmann F, Muche R, neo.nEURO.network Trial Participants: Systemic hypothermia after neonatal encephalopathy: outcomes of neo.nEURO.network RCT. Pediatrics 2010;126:e771-e778.
- Azzopardi DV, Strohm B, Edwards AD, Dyet L, Halliday HL, Juszczak E, Kapellou O, Levene M, Marlow N, Porter E, Thoresen M, Whitelaw A, Brocklehurst P: Moderate hypothermia to treat perinatal asphyxial encephalopathy. N Engl J Med 2009;361:1349-1358.
- Tagin MA, Woolcott CG, Vincer MJ, Whyte RK, Stinson DA: Hypothermia for neonatal hypoxic ischemic encephalopathy: an updated systematic review and meta-analysis. Arch Pediatr Adolesc Med 2012;166:558-566.
- Bayley N: Bayley Scales of Infant Development Ii; Psychological Corporation. San Antonio, Harcourt, Brace & Co, 1993.
- Hagberg B, Hagberg G, Beckung E, Uvebrant P: Changing panorama of cerebral palsy in Sweden. VIII. Prevalence and origin in the birth year period 1991-94. Acta Paediatr 2001;90:271-277.
- Guillet R, Edwards AD, Thoresen M, Ferriero DM, Gluckman PD, Whitelaw A, Gunn AJ: Seven- to eight-year follow-up of the CoolCap trial of head cooling for neonatal encephalopathy. Pediatr Res 2012;71:205-209.
- Gunn AJ, Bennet L, Gunning MI, Gluckman PD, Gunn TR: Cerebral hypothermia is not neuroprotective when started after postischemic seizures in fetal sheep. Pediatr Res 1999;46:274-280.
- Gunn AJ, Gunn TR, de Haan HH, Williams CE, Gluckman PD: Dramatic neuronal rescue with prolonged selective head cooling after ischemia in fetal lambs. J Clin Invest 1997;99:248-256.
- Rice JE 3rd, Vannucci RC, Brierley JB: The influence of immaturity on hypoxic-ischemic brain damage in the rat. Ann Neurol 1981;9:131-141.
- Robertson NJ, Tan S, Groenendaal F, van Bel F, Juul SE, Bennet L, Derrick M, Back SA, Valdez RC, Northington F, Gunn AJ, Mallard C: Which neuroprotective agents are ready for bench to bedside translation in the newborn infant? J Pediatr 2012;160:544-552.e4.
- Chakkarapani E, Dingley J, Liu X, Hoque N, Aquilina K, Porter H, Thoresen M: Xenon enhances hypothermic neuroprotection in asphyxiated newborn pigs. Ann Neurol 2010;68:330-341.
- Hobbs C, Thoresen M, Tucker A, Aquilina K, Chakkarapani E, Dingley J: Xenon and hypothermia combine additively, offering long-term functional and histopathologic neuroprotection after neonatal hypoxia/ischemia. Stroke 2008;39:1307-1313.
- Wu YW, Bauer LA, Ballard RA, Ferriero DM, Glidden DV, Mayock DE, Chang T, Durand DJ, Song D, Bonifacio SL, Gonzalez FF, Glass HC, Juul SE: Erythropoietin for neuroprotection in neonatal encephalopathy: safety and pharmacokinetics. Pediatrics 2012;130:683-691.
- Fan X, van Bel F, van der Kooij MA, Heijnen CJ, Groenendaal F: Hypothermia and erythropoietin for neuroprotection after neonatal brain damage. Pediatr Res 2013;73:18-23.
- Fang AY, Gonzalez FF, Sheldon RA, Ferriero DM: Effects of combination therapy using hypothermia and erythropoietin in a rat model of neonatal hypoxia-ischemia. Pediatr Res 2013;73:12-17.
- Cetinkaya M, Alkan T, Ozyener F, Kafa IM, Kurt MA, Koksal N: Possible neuroprotective effects of magnesium sulfate and melatonin as both pre- and post-treatment in a neonatal hypoxic-ischemic rat model. Neonatology 2011;99:302-310.
- Dingley J, Liu X, Tooley J, Chakkarapani E, Elstad M, Thoresen M: First human use of 50% xenon inhalation during cooling therapy for neonatal hypoxic-ischemic encephalopathy (HIE): the ‘CoolXenon' clinical feasibility study (platform presentation). Neonatal Society 2010 Autumn Meeting, London, 2010.