Determinants of outcomes after head cooling for neonatal encephalopathy

Imperial College London, Londinium, England, United Kingdom
PEDIATRICS (Impact Factor: 5.47). 06/2007; 119(5):912-21. DOI: 10.1542/peds.2006-2839
Source: PubMed


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
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    • "In infants with hypoxic ischaemic encephalopathy (HIE), multichannel EEG and amplitude integrated EEG (aEEG) are increasingly being used in the first 6 h after birth to help decide on eligibility for therapeutic hypothermia (Gluckman et al., 2005; Wyatt et al., 2007; Azzopardi et al., 2009), and for early prediction of longterm neurodevelopmental outcome (Pezzani et al., 1986; Wertheim et al., 1994; Selton and Andre, 1997; Toet et al., 1999; Pressler et al., 2001; ter Horst et al., 2004; Osredkar et al., 2005; Murray et al., 2009). Much of what is known about neonatal EEG is based on studies recorded in the first week of life. "
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    ABSTRACT: Objective: To examine sleep-wake cycle (SWC) composition of healthy term infants in the immediate postnatal period using EEG, and investigate factors that might influence it. Methods: Multichannel video-EEG was recorded for a median of 61.9min (IQR: 60.0-69.3). The absolute and relative scores of sleep states were calculated for each infant's recording. Parametric/non-parametric statistical tests and multiple linear regression analysis were used to investigate the influence of perinatal factors on SWC composition. Results: Eighty healthy term infants aged 1-36h were studied. A well-developed SWC was evident as early as within the first 6h after birth. The mean (SD) percentage of active sleep (AS) was 52.1% (12.9) and quiet sleep (QS) was 38.6% (12.5). AS was longer and QS shorter in infants delivered by elective caesarean section (CS) compared to infants delivered by vaginal delivery or emergency CS. Conclusions: This is the first large cohort EEG study that has quantified neonatal sleep. SWC is clearly present immediately after birth, it is dominated by AS, and is influenced by mode of delivery. Significance: This knowledge of the early neonatal EEG/SWC can be used as reference data for EEG studies of neurologically compromised infants.
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    • "A proposed diagram (Figure 8) is provided to show that JNK hyperactivation in the neurovascular unit (neurons, endothelial cells and microglia) after HI may be the potential link between being overweight from a small litter size and worsened HI injury in the neonatal brain. Our findings are consistent with a clinical report that evaluated the factors determining the treatment efficacy of head cooling hypothermia in newborns with HI encephalopathy [66]. The study found that larger infants (birth weights of ≥ 25th percentile) displayed a lower frequency of favorable outcomes in the control group, but a greater improvement with cooling. "
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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. "

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