Hyperglycaemia in infants with hypoxic-ischaemic encephalopathy is associated with improved outcomes after therapeutic hypothermia: A post hoc analysis of the CoolCap Study

Sudeepta K. Basu, Jason L. Salemi, Alistair J. Gunn, Jeffrey R. Kaiser, P. D. Gluckman, J. S. Wyatt, A. J. Gunn, J. S. Wyatt, R. Ballard, A. D. Edwards, D. M. Ferriero, P. D. Gluckman, A. J. Gunn, R. Polin, C. Robertson, A. Whitelaw, R. Soll, M. Bracken, C. Palmer, M. HeymannA. Wilkinson, J. R. Kaiser, M. Battin, D. Armstrong, J. Khan, T. Raju, R. Polin, R. Sahni, U. Sanocka, A. Rosenberg, J. Paisley, R. Goldberg, M. Cotton, A. Peliowski, E. Phillipos, D. Azzopardi, A. D. Edwards, F. Northington, J. Barks, S. Donn, B. Couser, D. Durand, K. Sekar, D. Davis, M. Blayney, S. Adeniyi-Jones, T. Yanowitz, R. Guillet, N. Laroia, N. Finer, for the CoolCap Study Group

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)F299-F306
JournalArchives of Disease in Childhood: Fetal and Neonatal Edition
Issue number4
StatePublished - Jul 1 2017


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

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Obstetrics and Gynecology

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