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Hyperglycaemia in infants with hypoxic–ischaemic encephalopathy is associated with improved outcomes after therapeutic hypothermia: a post hoc analysis of the CoolCap Study
  1. Sudeepta K Basu1,2,
  2. Jason L Salemi3,
  3. Alistair J Gunn4,
  4. Jeffrey R Kaiser5
  5. for the CoolCap Study Group
    1. 1Department of Pediatrics, Children's National Medical Center, Washington DC, USA
    2. 2Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA
    3. 3Department of Family and Community Medicine, Baylor College of Medicine, Houston, Texas, USA
    4. 4Department of Physiology, University of Auckland, Auckland, New Zealand
    5. 5Departments of Pediatrics and Obstetrics & Gynecology, Baylor College of Medicine, Houston, Texas, USA
    1. Correspondence to Dr Jeffrey R. Kaiser, Departments of Pediatrics and Obstetrics & Gynecology, Baylor College of Medicine, 6621 Fannin Street, MC: WT 6-104, Houston, TX 77030, USA; jrkaiser{at}


    Objective To investigate whether glycaemic profile is associated with multiorgan dysfunction and with response to hypothermia after perinatal hypoxic–ischaemic encephalopathy (HIE).

    Design Post hoc analysis of the CoolCap Study.

    Setting 25 perinatal centres in UK, USA and New Zealand during 1999–2002.

    Patients 194/234 (83%) infants of ≥36 weeks' gestation with moderate-to-severe HIE enrolled in the CoolCap Study with documented plasma glucose levels and follow-up outcome.

    Intervention Infants were randomised to head cooling for 72 hours starting within 6 hours of birth or standard care. Plasma glucose levels were measured at predetermined time intervals after randomisation.

    Main outcome measure Unfavourable primary outcome was defined as death and/or severe neurodevelopmental disability at 18 months. Glycaemic profile (hypoglycaemia (≤40 mg/dL, ≤2.2 mmol/L), hyperglycaemia (>150 mg/dL, >8.3 mmol/L) and normoglycaemia) during 12 hours after randomisation was investigated for association with multiorgan dysfunction or risk reduction of primary outcome after hypothermia treatment.

    Results Hypoglycaemia but not hyperglycaemia was associated with more deranged multiorgan function parameters (mean pH 7.23 (SD 0.16) vs 7.36 (0.13), p<0.001; aspartate transaminase 2101 (2450) vs 318 (516) IU/L, p=0.002; creatinine 1.95 (0.59) vs 1.26 (0.5) mg/dL, p<0.001) compared with normoglycaemia. After adjusting for Sarnat stage and 5 min Apgar score, only hyperglycaemic infants randomised to hypothermia had reduced risk of unfavourable outcome (adjusted risk ratio: 0.80, 95% CI 0.66 to 0.99), whereas hypoglycaemic and normoglycaemic infants did not.

    Conclusions Early glycaemic profile in infants with moderate-to-severe HIE may help to identify risk of multiorgan dysfunction and response to therapeutic hypothermia.

    Trial registration number NCT00383305.

    • neonatal hypoxic ischaemic encephalopathy
    • hypoglycaemia
    • hyperglycaemia
    • CoolCap Study
    • response to hypothermia treatment

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    • Collaborators Executive Committee: P.D. Gluckman (chair, co-principal investigator), J.S. Wyatt (co-principal investigator) and A.J. Gunn (scientific officer). SAC: J.S. Wyatt (chair), R. Ballard, A.D. Edwards, D.M. Ferriero, P.D. Gluckman, A.J. Gunn, R. Polin, C. Robertson and A. Whitelaw. Data Safety Committee: R. Soll (chair), M. Bracken, C. Palmer, M. Heymann and A.Wilkinson. Hospital Investigators: J.R. Kaiser (Arkansas Children's Hospital, 11 patients), M. Battin, D. Armstrong (University of Auckland-National Women's Hospital, NZ, 11 patients), J. Khan (Children's Memorial Hospital and Prentice Women's Hospital of Northwestern Memorial Hospital, three patients), T. Raju (University of Illinois at Chicago, one patient), R. Polin, R. Sahni, U. Sanocka (Children's Hospital of New York-Presbyterian, Columbia University, 18 patients), A. Rosenberg, J. Paisley (Children's Hospital of Denver, 23 patients), R. Goldberg, M. Cotton (Duke University, 14 patients), A. Peliowski, E. Phillipos (Royal Alexandra Hospital/University of Alberta Hospital, 20 patients), D. Azzopardi, A.D. Edwards (Hammersmith Hospital, London, UK, one patient), F. Northington (Johns Hopkins University, two patients), J. Barks, S. Donn (University of Michigan-Mott Children's Hospital, 12 patients), B. Couser (Children's Hospital and Clinics of Minneapolis, 16 patients), D. Durand (Children's Hospital and Research Centre at Oakland, eight patients), K. Sekar (Children's Hospital of Oklahoma, four patients), D. Davis, M. Blayney (Children's Hospital of Eastern Ontario/The Ottawa Hospital, one patient), S. Adeniyi-Jones (AI Dupont Children's Hospital at Thomas Jefferson University, six patients), T. Yanowitz (Magee Women's Hospital/ Children's Hospital of Pittsburgh, 10 patients), R. Guillet, N. Laroia (Golisano Children's Hospital at Strong, 10 patients), N. Finer, F. Mannino (University of California San Diego Medical Centre (Hillcrest), eight patients), J. Partridge (University of California San Francisco Children's Hospital, two patients), D. Davidson (Schneider Children's Hospital, 14 patients), A. Whitelaw (Southmead Hospital. Bristol, UK, 13 patients), M. Thoresen (St. Michael's Hospital, Bristol, UK, eight patients), J.S. Wyatt, F. O'Brien (University College Hospital, London, UK, four patients), B. Walsh (Vanderbilt Children's Hospital, 13 patients), J. Perciaccante and M. O'Shea (Wake Forest University Baptist Medical Centre, one patient). Manufacturer's Representatives: J. Jones, T. Weiler, J. Mullane, D. Hammond and J. Parnell (Olympic Medical, Seattle, Washington, WA, USA).

    • Contributors SKB: conceptualised and designed the study, drafted the initial manuscript and approved the final manuscript as submitted. JLS: performed data analysis, summarised results, critically reviewed the manuscript and approved the final manuscript as submitted. AJG and JRK: conceptualised and designed the study, supervised data analysis and interpretation, reviewed and revised the manuscript and approved the final manuscript as submitted. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

    • Funding CoolCap Study was supported by the Olympic Medical, Seattle, Washington, WA, USA. No funding was received for this post hoc analysis. Olympic Medical supported the original CoolCap Study financially, provided administrative support to the sites, supplied the aEEG monitors and the cooling devices and monitored initial data recording and accuracy, but had no input into the manuscript. The funding sources had no role in the analysis and interpretation of the data; preparation, review or approval of this manuscript and decision to submit this manuscript for publication.

    • Competing interests None declared.

    • Ethics approval Institutional review boards at each participating institute in CoolCap Study approved the original study. The current paper is a secondary analysis of the original study.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data sharing statement All data are available to the CoolCap Study steering committee and AJG.