Hyperglycaemia and outcome in neonates with hypoxic-ischaemic encephalopathy

Main Article Content

M Sichula
S Pillay
V Nakibuuka
M Harrison
A Horn


Background. Hypoxic-ischaemic encephalopathy (HIE) remains a leading cause of death and disability in term neonates despite therapeutic hypothermia. Hyperglycaemia in the first 12 hours of life is associated with poor outcomes in some studies. This relationship has not yet been explored in South African (SA) cohorts.

Objective. To describe the association between hyperglycaemia (in the first 12 hours of life) and poor outcome, which was defined as death or a severely abnormal amplitude-integrated electroencephalogram (aEEG) at 48 hours, in neonates with moderate-to-severe HIE who were treated with hypothermia at an SA tertiary hospital.

Methods. Folders from a database of 57 neonates with moderate-to-severe HIE treated with hypothermia between January 2011 and December 2012, were reviewed to obtain glycaemic profiles. Maternal and neonatal characteristics and outcomes were extracted from the database.

Results. Only 47 neonates had adequate glucose and aEEG data. Seventeen neonates (36%) had hyperglycaemia (>8.3 mmol/L), 25 (53%) were normoglycaemic and 5 neonates (10%) were hypoglycaemic (<2.3 mmol/L). Hyperglycaemia was only associated with death or severely abnormal aEEG at a glucose value ≥25.6 mmol/L. Hyperglycaemia was significantly associated with a low 5-minute Apgar score (p=0.007), severely abnormal aEEG at 6 hours (p=0.029), and a higher HIE score at 6 hours (p=0.002). Hyperglycaemia was associated with death (odds ratio 10; 95% confidence interval 1 - 96; p=0.045), but the association was not independent of the 5-minute Apgar score.

Conclusion. Early hyperglycaemia in neonates with moderate-to-severe HIE was associated with disease severity at birth and death despite cooling.

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How to Cite
Hyperglycaemia and outcome in neonates with hypoxic-ischaemic encephalopathy. (2024). South African Journal of Child Health, 18(1), e1028. https://doi.org/10.7196/
Author Biographies

M Sichula, Department of Paediatrics and Child Health, University of Cape Town

Mwiche is a general paediatrician originally from Zambia. She completed her undergraduate degree at the University of Pretoria in Gauteng, South Africa. She relocated from Gauteng to the Western Cape, where she started and completed training as a specialist paediatrician and achieved masters in paediatrics, at the University of Cape Town. Her masters research project re-ignited her passion for developmental issues and concerns in children of all ages and highlighted that healthy children start with healthy babies. She is passionate about neurodevelopment and respiratory conditions in children and will continue to focus my career on these aspects.

S Pillay, Neonatal Medicine, Department of Paediatrics and Child Health, University of Cape Town

Shakti’s undergraduate medical training at the University of Witwatersrand was followed by internship in Cape Town and community service in rural Kwa-Zulu Natal. She trained and specialized as a paediatrician and subsequently a neonatologist at the University of Cape Town (UCT). She was appointed senior clinical researcher and subsequently sub-specialist in neonatology at Groote Schuur Hospital, Cape Town, in 2019. Her paediatric and neonatal  research interests have focused on haematological, respiratory, infection-related, and neurological areas. She is co-investigator on studies with obstetrics and emergency departments and a multi-centre antibiotic stewardship study and is UCT site Co-PI for the national Neonatal Encephalopathy with suspected HIE (NESHIE) study. She manages the junior staff and is passionate about implementation of governance and ethical principles. She designed, developed and co-authored the content of the Neonatal Guide App and is a lead-author for South African Neonatal Guidelines.

V Nakibuuka, Department of Pediatrics, Nsambya Hospital, Kampala Uganda

Victoria is a paediatrician with 15 years’ experience, including sub-specialization in neonatology in Cape Town, South Africa and 8 years’ neonatologist practice in a tertiary hospital in Uganda. She led the setting up of the first neonatal Intensive care unit and newborn units in Uganda at Nsambya Hospital and spear-headed the setting up of the first Human milk Bank in Uganda. She is involved in development of clinical guideline curriculae and training for neonatal trainees, nurses, postgraduates researchers and junior doctors. Her passion and primary area of interest is implementation research to improve the quality of life of newborns in Uganda. Other interests include improving preterm outcomes, preterm nutrition, perinatal asphyxia and neonatal infections.

M Harrison , Neonatal Medicine, Department of Paediatrics and Child Health, University of Cape Town

Michael’s undergraduate training was at the University of Cape Town and he left a few years later to train in the United Kingdom. He completed his paediatric training in London, later sub-specialising in Neonatal Medicine which incorporated a two-year research project into magnetic resonance imaging of preterm infant lungs. In 2002 he was appointed as a consultant and senior lecturer in neonatal medicine at the Hammersmith Hospital, Imperial College, London. In 2008 he was appointed senior sub-specialist in neonatology at Groote Schuur Hospital, Cape Town where he was later appointed to his current position as head of division in February 2011. Problems at birth remain a major health issue for South Africa and affected infants are drawn disproportionately from disadvantaged populations - he is passionate about addressing these issues and his research is focused on this.

A Horn, Neonatal Medicine, Department of Paediatrics and Child Health, University of Cape Town

Alan is Associate Professor of Paediatrics and Neonatal Medicine at Groote Schuur Hospital and University of Cape Town (UCT). His under-graduate training was in Cape Town, South Africa. He subsequently trained in paediatrics and neonatology in  the UK and South Africa. He was appointed as Sub-specialist in Neonatology at Groote Schuur Hospital, Cape Town, in 2003 and helped facilitate the modernisation of the unit with the introduction of aEEG, therapeutic hypothermia and neonatologist-performed echocardiograph. He chairs the University Specialist Training Committee, assists with developing national guidelines and is am the founding president of the United South African Neonatal Association (USANA). He wrote the first editions of “Neonatal Guidelines and Drug Doses”. His main research interests are hypoxic ischaemic encephalopathy (HIE) and therapeutic hypothermia. He is UCT site Co-PI for the national Neonatal Encephalopathy with suspected HIE (NESHIE) study and a member of the National workplace-based assessment steering committee.

How to Cite

Hyperglycaemia and outcome in neonates with hypoxic-ischaemic encephalopathy. (2024). South African Journal of Child Health, 18(1), e1028. https://doi.org/10.7196/


Blencowe H, Vos T, Lee AC, et al. Estimates of neonatal morbidities and disabilities at regional and global levels for 2010: Introduction, methods overview, and relevant findings from the Global Burden of Disease Study. Pediatr Res 2013;74(Suppl 1):4-16. https://doi.org/10.1038/pr.2013.203

Jacobs SE, Berg M, Hunt R, et al. Cooling for newborns with hypoxic ischaemic encephalopathy. Cochrane Database Syst Rev 2013(1):CD003311. https://doi. org/10.1002/14651858.cd003311.pub3

Pappas A, Shankaran S, McDonald SA, et al. Cognitive outcomes after neonatal encephalopathy. Pediatrics 2015;135(3):e624-634. https://doi. org/10.1542/peds.2014-1566

Global Burden of Disease Pediatrics Collaboration. Global and national burden of diseases and injuries among children and adolescents between 1990 and 2013: Findings from the Global Burden of Disease 2013 Study. JAMA Pediatr 2016;170(3):267-287. https://doi.org/10.1001/jamapediatrics.2015.4276

Tam EW, Haeusslein LA, Bonifacio SL, et al. Hypoglycemia is associated with increased risk for brain injury and adverse neurodevelopmental outcome in neonates at risk for encephalopathy. J Pediatr 2012;161(1):88-93. https://doi. org/10.1016/j.jpeds.2011.12.047

Burns CM, Rutherford MA, Boardman JP, Cowan FM. Patterns of cerebral injury and neurodevelopmental outcomes after symptomatic neonatal hypoglycemia. Pediatrics 2008;122(1):65-74. https://doi.org/10.1542/peds.2007-2822

McGowan JE, Chen L, Gao D, Trush M, Wei C. Increased mitochondrial reactive oxygen species production in newborn brain during hypoglycemia. Neurosci Lett 2006;399(1-2):111-114. https://doi.org/10.1016/j.neulet.2006.01.034

Nadeem M, Murray DM, Boylan GB, Dempsey EM, Ryan CA. Early blood glucose profile and neurodevelopmental outcome at two years in neonatal hypoxic-ischaemic encephalopathy. BMC Pediatr 2011;11:2-7. https://doi. org/10.1186/1471-2431-11-10

BasuSK,KaiserJR,GuffeyD,etal.Hypoglycaemiaandhyperglycaemiaareassociated with unfavourable outcome in infants with hypoxic ischaemic encephalopathy: A post hoc analysis of the CoolCap Study. Arch Dis Child Fetal Neonatal Ed 2016;101(2):F149-F155. https://doi.org/10.1136/archdischild-2015-308733

Spies EE, Lababidi SL, McBride MC. Early hyperglycemia is associated with poor gross motor outcome in asphyxiated term newborns. Pediatr Neurol 2014;50(6):586-590. https://doi.org/10.1016/j.pediatrneurol.2014.01.043

Basu SK, Salemi JL, Gunn AJ, Kaiser JR, for the CoolCap Study Group. Hyperglycaemia in infants with hypoxic-ischaemic encephalopathy is associated with improved outcomes after therapeutic hypothermia: a post hoc analysis of the CoolCap Study. Arch Dis Child Fetal Neonatal Ed 2017;102(4):F299-F306. https://doi.org/10.1136/archdischild-2016-311385

NakibuukaV.Theinfluenceofbirthsiteonshort-termoutcomesofencephalopathic newborn infants treated with therapeutic hypothermia at Groote Schuur Hospital, Cape Town, South Africa. MPhil thesis. Cape Town: University of Cape Town, 2015. http://hdl.handle.net/11427/15738 (accessed 23 August 2023)

Horn AR, Swingler GH, Myer L, et al. Early clinical signs in neonates with hypoxic ischemic encephalopathy predict an abnormal amplitude-integrated electroencephalogram at age 6 hours. BMC Pediatr 2013;13:52. https://doi. org/10.1186/1471-2431-13-52

Toet MC, Hellström-Westas L, Groenendaal F, Eken P, de Vries LS. Amplitude- integrated EEG 3 and 6 hours after birth in full-term neonates with hypoxic- ischaemic encephalopathy. Arch Dis Child Fetal Neonatal Ed 1999;81(1):F19- 23. https://doi.org/10.1136/fn.81.1.f19

Thoresen M, Hellstrom-Westas L, Liu X, de Vries LS. Effect of hypothermia on amplitude-integrated electroencephalogram in infants with asphyxia. Pediatrics 2010;126(1):e131-139. https://doi.org/10.1542/peds.2009-2938

Thompson CM, Puterman AS, Linley LL, et al. The value of a scoring system for hypoxic ischaemic encephalopathy in predicting neurodevelopmental outcome. Acta Paediatrica 1997;86(7):757-761. https://doi.org/10.1111/j.1651-2227.1997. tb08581.x

Shankaran S, Laptook AR, Ehrenkranz RA, et al. Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N Engl J Med 2005;353(15):1574- 1584. https://doi.org/10.1056/nejmcps050929

Chouthai NS, Sobczak H, Khan R, et al. Hyperglycemia is associated with poor outcome in newborn infants undergoing therapeutic hypothermia for hypoxic ischemic encephalopathy. J Neonatal Perinatal Med 2015;8(2):125-131. https:// doi.org/10.3233/npm-15814075

Montaldo P, Caredda E, Pugliese U, et al. Continous glucose monitoring profiles during therapeutic hypothermia in encephalopathic infants with unfavourable outcome. Pediatr Res 2020;88:218-224. https://doi.org/10.1038/s41390-020- 0827-4

Tam EWY, Kamino D, Shatil AS, et al. Hyperglycemia associated with acute brain injury in neonatal encephalopathy. Neuroimage Clin 2021;32:102835. https://doi.org/10.1016/j.nicl.2021.102835

Sarkar S, Donn SM, Bapuraj JR, et al. The relationship between clinically identifiable intrapartum sentinel events and short-term outcome after therapeutic hypothermia. J Pediatr 2011;159(5):726-730. https://doi.org/10.1016/j. jpeds.2011.04.014

Shankaran S, Laptook AR, McDonald SA, et al. Acute perinatal sentinel events, neonatal brain injury pattern, and outcome of infants undergoing a trial of hypothermia for neonatal hypoxic-ischemic encephalopathy. J Pediatr 2017;180:275-278 e272. https://doi.org/10.1016/j.jpeds.2016.09.026

Bonifacio SL, Glass HC, Vanderpluym J, et al. Perinatal events and early magnetic resonance imaging in therapeutic hypothermia. J Pediatr 2011;158(3):360-365. https://doi.org/10.1016/j.jpeds.2010.09.003

Pinchefsky EF, Hahn CD, Kamino D, et al. Hyperglycemia and glucose variability are associated with worse brain function and seizures in neonatal encephalopathy: A prospective cohort study. J Pediatr 2019;209:23-32. https:// doi.org/10.1016/j.jpeds.2019.02.027

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