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Is therapeutic hypothermia for hypoxic ischaemic encephalopathy beneficial in late preterm babies?

Three Part Question

In a late premature baby (34 weeks) [patient] does therapeutic
hypothermia [intervention] compared to normothermia [comparision] reduce
the neurological adverse outcomes of moderate hypoxic ischaemic encephalopathy?

Clinical Scenario

A 34 week baby has been delivered following a uterine rupture and is pale and floppy with no heart rate. Resuscitation is started and the baby quickly responds. Apgar scores are 11, 25 and 410. One hour later, the baby develops abnormal movements consistent with a seizure.
Blood gas analysis at this time shows: pH 6.90, PCO2 6.5, PO2 8.2, BE -14, Lactate 11.
Although by gestation this baby is one week below the 35 week limit suggested in the national guideline for therapeutic hypothermia, should this baby be considered for cooling?

Search Strategy

Online search performed - OVID interface
key words 'Preterm’, ‘Premature’, ‘Hypothermia’, ‘Hypoxic ischaemic encephalopathy’,
‘cooling’, ‘HIE’, ‘encephalopathy’ and ‘late preterm’.

Search Outcome

Secondary sources identified: Cochrane Library-one review article.
Primary sources identified: Medline, Embase, CINAHL databases were searched. There were 11 articles in Medline, 13 articles in Embase and 3 articles in CINAHL. The articles found were in turn hand-searched to identify any further relevant references.

Relevant Paper(s)

Author, date and country Patient group Study type (level of evidence) Outcomes Key results Study Weaknesses
Austin, T et al
Not applicableReview, expert consensusExpert consensusCautiously advocates cooling for 33-36 week babies with clear diagnosis of hypoxic ischaemic encephalopathy
Gunn, AJ, Bennet L
New Zealand
Not applicableReviewMRI evidence of brain injurySignificantly reduced in preterm sheep which underwent moderate therapeutic hypothermiaBased on animal models of preterm brain injury


There is limited evidence and few studies that evaluate the effectiveness and benefit of therapeutic hypothermia in 32-35 week gestation babies. The published literature on this topic consists of animal studies, case reports and consensus opinions. The only published guidance cautiously advocates cooling for 33-36 week infants, if there is a strong clinical suspicion of an acute hypoxic-ischaemic event. However, data from large randomised controlled studies is lacking. Further research is needed before cooling can be routinely considered in 32-35 week babies. Until then it is crucially important to continue to enter all babies cooled outside of criteria into the national cooling register so that they are appropriately followed up and that data can be analysed retrospectively.

Clinical Bottom Line

Babies with HIE born between 32-35 weeks who fulfil the criteria for cooling should be promptly discussed directly with a local cooling centre. Any consideration to cool outside nationally defined criteria should be clearly discussed with parents with the risks and benefits outlined.


  1. Laura, F et al Therapeutic hypothermia in a late preterm infant Journal of Maternal Fetal and Neonatal Medicine 2012 Apr;25 Suppl 1:125-7
  2. Austin, T et al To cool or not to cool? Hypothermia treatment outside trial criteria Archives of disease in childhood - fetal and neonatal edition 2013 Sep;98(5):F451-3
  3. Gunn, AJ, Bennet L Brain cooling for preterm infants Clinical Perinatology 2008 Dec;35(4):735-48
  4. Walsh W et al Pilot Study of Head Cooling in Preterm Infants With Hypoxic Ischemic Encephalopathy Results not yet published Not applicable