Gluckman PD, Wyatt JS, Azzopardi D, Ballard R, Edwards AD, Ferriero DM, Polin RA, Robertson CM, Thoresen M, Whitelaw A, Gunn AJSelective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trial. Lancet 365:663-670

The Liggins Institute, University of Auckland, Auckland, New Zealand.
The Lancet (Impact Factor: 45.22). 02/2005; 365(9460):663-70. DOI: 10.1016/S0140-6736(05)17946-X
Source: PubMed


Cerebral hypothermia can improve outcome of experimental perinatal hypoxia-ischaemia. We did a multicentre randomised controlled trial to find out if delayed head cooling can improve neurodevelopmental outcome in babies with neonatal encephalopathy.
234 term infants with moderate to severe neonatal encephalopathy and abnormal amplitude integrated electroencephalography (aEEG) were randomly assigned to either head cooling for 72 h, within 6 h of birth, with rectal temperature maintained at 34-35 degrees C (n=116), or conventional care (n=118). Primary outcome was death or severe disability at 18 months. Analysis was by intention to treat. We examined in two predefined subgroup analyses the effect of hypothermia in babies with the most severe aEEG changes before randomisation--ie, severe loss of background amplitude, and seizures--and those with less severe changes.
In 16 babies, follow-up data were not available. Thus in 218 infants (93%), 73/110 (66%) allocated conventional care and 59/108 (55%) assigned head cooling died or had severe disability at 18 months (odds ratio 0.61; 95% CI 0.34-1.09, p=0.1). After adjustment for the severity of aEEG changes with a logistic regression model, the odds ratio for hypothermia treatment was 0.57 (0.32-1.01, p=0.05). No difference was noted in the frequency of clinically important complications. Predefined subgroup analysis suggested that head cooling had no effect in infants with the most severe aEEG changes (n=46, 1.8; 0.49-6.4, p=0.51), but was beneficial in infants with less severe aEEG changes (n=172, 0.42; 0.22-0.80, p=0.009).
These data suggest that although induced head cooling is not protective in a mixed population of infants with neonatal encephalopathy, it could safely improve survival without severe neurodevelopmental disability in infants with less severe aEEG changes.

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Available from: Marianne Thoresen
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    • "Hypoxic–ischemic encephalopathy is the most common cause of brain injury in term newborns. Therapeutic hypothermia is currently the only existing treatment to minimize brain injury in these newborns, with decreased death and disability rates at 12–18 months and beyond (Azzopardi et al., 2009; Eicher et al., 2005a, b; Gluckman et al., 2005; Jacobs et al., 2007; Shankaran et al., 2005; Shankaran et al., 2012). However , some newborns still develop brain injury despite this treatment (Barks, 2008; Higgins et al., 2006; Higgins and Shankaran, 2009). "
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    • "Neonatal hypoxic–ischemic encephalopathy (HIE) remains a serious condition that causes significant mortality and morbidity in near-term and term newborns (Gluckman et al., 2005; Shankaran et al., 2005). Brain hypoxia and ischemia due to systemic hypoxemia and reduced cerebral blood flow (CBF) are the primary causes of neonatal HIE accompanied by gray and white matter injuries occurring in neonates (Ferriero, 2004; Grow and Barks, 2002). "
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