A Randomized Clinical Trial of Therapeutic Hypothermia Mode during Transport for Neonatal Encephalopathy

Published:February 12, 2015DOI:


      To determine if temperature regulation is improved during neonatal transport using a servo-regulated cooling device when compared with standard practice.

      Study design

      We performed a multicenter, randomized, nonmasked clinical trial in newborns with neonatal encephalopathy cooled during transport to 9 neonatal intensive care units in California. Newborns who met institutional criteria for therapeutic hypothermia were randomly assigned to receive cooling according to usual center practices vs device servo-regulated cooling. The primary outcome was the percentage of temperatures in target range (33°-34°C) during transport. Secondary outcomes included percentage of newborns reaching target temperature any time during transport, time to target temperature, and percentage of newborns in target range 1 hour after cooling initiation.


      One hundred newborns were enrolled: 49 to control arm and 51 to device arm. Baseline demographics did not differ with the exception of cord pH. For each subject, the percentage of temperatures in the target range was calculated. Infants cooled using the device had a higher percentage of temperatures in target range compared with control infants (median 73% [IQR 17-88] vs 0% [IQR 0-52], P < .001). More subjects reached target temperature during transport using the servo-regulated device (80% vs 49%, P <.001), and in a shorter time period (44 ± 31 minutes vs 63 ± 37 minutes, P = .04). Device-cooled infants reached target temperature by 1 hour with greater frequency than control infants (71% vs 20%, P < .001).


      Cooling using a servo-regulated device provides more predictable temperature management during neonatal transport than does usual care for outborn newborns with neonatal encephalopathy.
      CPeTS (California Perinatal Transport System), CPQCC (California Perinatal Quality Care Collaborative), FDA (Food and Drug Administration)
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic and Personal
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to The Journal of Pediatrics
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Shah P.S.
        Hypothermia: a systematic review and meta-analysis of clinical trials.
        Semin Fetal Neonatal Med. 2010; 15: 238-246
        • Shankaran S.
        • Laptook A.R.
        • Ehrenkranz R.A.
        • Tyson J.E.
        • McDonald S.A.
        • Donovan E.F.
        • et al.
        Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy.
        N Engl J Med. 2005; 353: 1574-1584
        • Jacobs S.E.
        • Morley C.J.
        • Inder T.E.
        • Stewart M.J.
        • Smith K.R.
        • McNamara P.J.
        • et al.
        Whole-body hypothermia for term and near-term newborns with hypoxic-ischemic encephalopathy: a randomized controlled trial.
        Arch Pediatr Adolesc Med. 2011; 165: 692-700
        • Azzopardi D.V.
        • Strohm B.
        • Edwards A.D.
        • Dyet L.
        • Halliday H.L.
        • Juszczak E.
        • et al.
        Moderate hypothermia to treat perinatal asphyxial encephalopathy.
        N Engl J Med. 2009; 361: 1349-1358
        • Eicher D.J.
        • Wagner C.L.
        • Katikaneni L.P.
        • Hulsey T.C.
        • Bass W.T.
        • Kaufman D.A.
        • et al.
        Moderate hypothermia in neonatal encephalopathy: efficacy outcomes.
        Pediatr Neurol. 2005; 32: 11-17
        • Simbruner G.
        • Mittal R.A.
        • Rohlmann F.
        • Muche R.
        Systemic hypothermia after neonatal encephalopathy: outcomes of RCT.
        Pediatrics. 2010; 126: e771-e778
        • Gluckman P.D.
        • Wyatt J.S.
        • Azzopardi D.
        • Ballard R.
        • Edwards A.D.
        • Ferriero D.M.
        • et al.
        Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trial.
        Lancet. 2005; 365: 663-670
        • Eicher D.J.
        • Wagner C.L.
        • Katikaneni L.P.
        • Hulsey T.C.
        • Bass W.T.
        • Kaufman D.A.
        • et al.
        Moderate hypothermia in neonatal encephalopathy: safety outcomes.
        Pediatr Neurol. 2005; 32: 18-24
        • Jacobs S.E.
        • Berg M.
        • Hunt R.
        • Tarnow-Mordi W.O.
        • Inder T.E.
        • Davis P.G.
        Cooling for newborns with hypoxic ischaemic encephalopathy.
        Cochrane Database Syst Rev. 2013; 1: CD003311
        • Gunn A.J.
        • Bennet L.
        • Gunning M.I.
        • Gluckman P.D.
        • Gunn T.R.
        Cerebral hypothermia is not neuroprotective when started after postischemic seizures in fetal sheep.
        Pediatr Res. 1999; 46: 274-280
        • Gunn A.J.
        • Gunn T.R.
        • de Haan H.H.
        • Williams C.E.
        • Gluckman P.D.
        Dramatic neuronal rescue with prolonged selective head cooling after ischemia in fetal lambs.
        J Clin Invest. 1997; 99: 248-256
        • Gunn A.J.
        • Gunn T.R.
        • Gunning M.I.
        • Williams C.E.
        • Gluckman P.D.
        Neuroprotection with prolonged head cooling started before postischemic seizures in fetal sheep.
        Pediatrics. 1998; 102: 1098-1106
        • Iwata O.
        • Iwata S.
        • Thornton J.S.
        • De Vita E.
        • Bainbridge A.
        • Herbert L.
        • et al.
        “Therapeutic time window” duration decreases with increasing severity of cerebral hypoxia-ischaemia under normothermia and delayed hypothermia in newborn piglets.
        Brain Res. 2007; 1154: 173-180
        • Thoresen M.
        • Tooley J.
        • Liu X.
        • Jary S.
        • Fleming P.
        • Luyt K.
        • et al.
        Time is brain: starting therapeutic hypothermia within three hours after birth improves motor outcome in asphyxiated newborns.
        Neonatology. 2013; 104: 228-233
        • Zhou W.H.
        • Cheng G.Q.
        • Shao X.M.
        • Liu X.Z.
        • Shan R.B.
        • Zhuang D.Y.
        • et al.
        Selective head cooling with mild systemic hypothermia after neonatal hypoxic-ischemic encephalopathy: a multicenter randomized controlled trial in China.
        J Pediatr. 2010; 157 (372.e1-3): 367-372
        • Akula V.P.
        • Gould J.B.
        • Davis A.S.
        • Hackel A.
        • Oehlert J.
        • Van Meurs K.P.
        Therapeutic hypothermia during neonatal transport: data from the California Perinatal Quality Care Collaborative (CPQCC) and California Perinatal Transport System (CPeTS) for 2010.
        J Perinatol. 2013; 33: 194-197
        • Fairchild K.
        • Sokora D.
        • Scott J.
        • Zanelli S.
        Therapeutic hypothermia on neonatal transport: 4-year experience in a single NICU.
        J Perinatol. 2010; 30: 324-329
        • O'Reilly K.M.
        • Tooley J.
        • Winterbottom S.
        Therapeutic hypothermia during neonatal transport.
        Acta Paediatr. 2011; 100 (discussion e49): 1084-1086
        • Kendall G.S.
        • Kapetanakis A.
        • Ratnavel N.
        • Azzopardi D.
        • Robertson N.J.
        Passive cooling for initiation of therapeutic hypothermia in neonatal encephalopathy.
        Arch Dis Child Fetal Neonatal Ed. 2010; 95: F408-F412
        • Harris P.A.
        • Taylor R.
        • Thielke R.
        • Payne J.
        • Gonzalez N.
        • Conde J.G.
        Research electronic data capture (REDCap)—a metadata-driven methodology and workflow process for providing translational research informatics support.
        J Biomed Inform. 2009; 42: 377-381
        • Natarajan G.
        • Pappas A.
        • Shankaran S.
        • Laptook A.R.
        • Walsh M.
        • McDonald S.A.
        • et al.
        Effect of inborn vs. outborn delivery on neurodevelopmental outcomes in infants with hypoxic-ischemic encephalopathy: secondary analyses of the NICHD whole-body cooling trial.
        Pediatr Res. 2012; 72: 414-419
        • Akula V.P.
        • Davis A.S.
        • Gould J.B.
        • Van Meurs K.
        Therapeutic hypothermia during neonatal transport: current practices in California.
        Am J Perinatol. 2012; 29: 319-326
        • Chaudhary R.
        • Farrer K.
        • Broster S.
        • McRitchie L.
        • Austin T.
        Active versus passive cooling during neonatal transport.
        Pediatrics. 2013; 132: 841-846