CoolCap Study Group. Determinants of outcomes after head cooling for neonatal encephalopathy

Imperial College London, Londinium, England, United Kingdom
PEDIATRICS (Impact Factor: 5.3). 06/2007; 119(5):912-21. DOI: 10.1542/peds.2006-2839
Source: PubMed

ABSTRACT The goal of this study was to evaluate the role of factors that may determine the efficacy of treatment with delayed head cooling and mild systemic hypothermia for neonatal encephalopathy.
A total of 218 term infants with moderate to severe neonatal encephalopathy plus abnormal amplitude-integrated electroencephalographic recordings, assigned randomly to head cooling for 72 hours, starting within 6 hours after birth (with the rectal temperature maintained at 34.5 +/- 0.5 degrees C), or conventional care, were studied. Death or severe disability at 18 months of age was assessed in a multicenter, randomized, controlled study (the CoolCap trial).
Treatment, lower encephalopathy grade, lower birth weight, greater amplitude-integrated electroencephalographic amplitude, absence of seizures, and higher Apgar score, but not gender or gestational age, were associated significantly with better outcomes. In a multivariate analysis, each of the individually predictive factors except for Apgar score remained predictive. There was a significant interaction between treatment and birth weight, categorized as > or =25th or <25th percentile for term, such that larger infants showed a lower frequency of favorable outcomes in the control group but greater improvement with cooling. For larger infants, the number needed to treat was 3.8. Pyrexia (> or =38 degrees C) in control infants was associated with adverse outcomes. Although there was a small correlation with birth weight, the adverse effect of greater birth weight in control infants remained significant after adjustment for pyrexia and severity of encephalopathy.
Outcomes after hypothermic treatment were strongly influenced by the severity of neonatal encephalopathy. The protective effect of hypothermia was greater in larger infants.

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Available from: Marianne Thoresen, Aug 22, 2015
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    • "These clinical trials indicated that hypothermia can have moderate beneficial effects when the intervention is started within 6 h after the insult in term infants with mild HI damage. Unfortunately, there is little benefit in infants with severe HI brain damage (Jacobs et al., 2007; Wyatt et al., 2007). In addition, hypothermia has not been used in preterm infants. "
    Brain Behavior and Immunity 08/2010; 24. DOI:10.1016/j.bbi.2010.07.029 · 6.13 Impact Factor
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    • "These animal data are strongly supported by clinical observations. Relatively high body temperatures of infants during usual care after hypoxia–ischemia are associated with increased risk of adverse outcomes [16] [36]. "
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    ABSTRACT: Neonatal anoxia is an example of early-life threatening experience that might exert long-lasting behavioral disturbance. One of the consequences of neonatal asphyxia is hyperactivity in open-field test. Changes in open-field activity are coupled with changes in the function of the hypothalamic-pituitary-adrenal (HPA) axis. A critical determinant of the severity of hypoxic-ischemic brain injury in newborn rats is body temperature. Hyperthermia under anoxic conditions increases locomotor activity in the open-field test. Therefore, the aim of the present study was to test whether body temperature during neonatal anoxia can affect basal and stress-induced corticosterone secretion in rats. At the age of 2 days Wistar rat pups were exposed to anoxia in 100% nitrogen atmosphere. Rectal temperature was kept at 33 degrees C (typical for the rat pups), or was elevated to a level typical for febrile adults (39 degrees C). Control rats were exposed to atmospheric air under the respective thermal conditions. Basal and stress-induced corticosterone levels were assessed using sulphuric acid-induced fluorescence, on postnatal day 14. Body temperature during neonatal asphyxia altered the early developmental profile of plasma corticosterone. Hyperthermia under anoxic conditions decreased the corticosterone response to open-field stress. In conclusion, febrile body temperature changes corticosterone release, which might induce neurobehavioral disturbances. On the other hand, a protection against the HPA dysfunction can be achieved by the reduced physiological neonatal body temperature.
    Neuroscience Letters 03/2010; 472(1):68-72. DOI:10.1016/j.neulet.2010.01.060 · 2.06 Impact Factor
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    • "Higher core temperatures were associated with significant increases in risk of death or impairment in the control group (Laptook et al., 2008). In a secondary analysis of the Cool Cap trial, investigators also noted an association between elevated temperatures in the control group and increased risk of death or disability (Wyatt et al., 2007). Hyperthermia after brain injury adds to the risk of more severe neurologic damage, and studies in adults and pediatric subjects consistently support association between higher core temperatures and worse outcome (Dietrich and Bramlett, 2007; Bramlett and Dietrich, 2007). "
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    ABSTRACT: In this article, the role of hypothermia and neuroprotection for neonatal encephalopathy will be discussed. The incidence of encephalopathy due to hypoxia ischemia as well as the pathophysiology will be presented. The diagnosis of encephalopathy in full-term neonates will be discussed. The current management of brain injury that occurs with hypoxia ischemia and the role of hypothermia in preventing brain injury in fetal and neonatal animal models will be reviewed. The current data from randomized control trials of hypothermia as neuroprotection for full-term infants will be presented along with the results of meta-analyses of these trials. Lastly, the status of ongoing neonatal hypothermia trials will be summarized.
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