Moderate Hypothermia to Treat Perinatal Asphyxial Encephalopathy

Division of Clinical Sciences and Medical Research Council Clinical Sciences Centre, Hammersmith Hospital, Imperial College London, London, United Kingdom.
New England Journal of Medicine (Impact Factor: 55.87). 10/2009; 361(14):1349-58. DOI: 10.1056/NEJMoa0900854
Source: PubMed


Whether hypothermic therapy improves neurodevelopmental outcomes in newborn infants with asphyxial encephalopathy is uncertain.
We performed a randomized trial of infants who were less than 6 hours of age and had a gestational age of at least 36 weeks and perinatal asphyxial encephalopathy. We compared intensive care plus cooling of the body to 33.5 degrees C for 72 hours and intensive care alone. The primary outcome was death or severe disability at 18 months of age. Prespecified secondary outcomes included 12 neurologic outcomes and 14 other adverse outcomes.
Of 325 infants enrolled, 163 underwent intensive care with cooling, and 162 underwent intensive care alone. In the cooled group, 42 infants died and 32 survived but had severe neurodevelopmental disability, whereas in the noncooled group, 44 infants died and 42 had severe disability (relative risk for either outcome, 0.86; 95% confidence interval [CI], 0.68 to 1.07; P=0.17). Infants in the cooled group had an increased rate of survival without neurologic abnormality (relative risk, 1.57; 95% CI, 1.16 to 2.12; P=0.003). Among survivors, cooling resulted in reduced risks of cerebral palsy (relative risk, 0.67; 95% CI, 0.47 to 0.96; P=0.03) and improved scores on the Mental Developmental Index and Psychomotor Developmental Index of the Bayley Scales of Infant Development II (P=0.03 for each) and the Gross Motor Function Classification System (P=0.01). Improvements in other neurologic outcomes in the cooled group were not significant. Adverse events were mostly minor and not associated with cooling.
Induction of moderate hypothermia for 72 hours in infants who had perinatal asphyxia did not significantly reduce the combined rate of death or severe disability but resulted in improved neurologic outcomes in survivors. (Current Controlled Trials number, ISRCTN89547571.)

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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.
    Full-text · Article · Dec 2015 · Clinical neurophysiology: official journal of the International Federation of Clinical Neurophysiology
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    • "Mild encephalopathy may have a normal outcome, 20-40% of neonates with moderate encephalopathy can have an abnormal outcome and severe encephalopathy generally leads to neurological disability or death (Gray et al., 1993) in the majority of neonates. The results of several international trials has shown that early induced hypothermia is beneficial in HIE, improving survival and reducing neurological disability (Azzopardi et al., 2009). The treatment involves cooling the infant to a body temperature of between 32-34°C for 72hours without interruption. "
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    ABSTRACT: This work presents a novel automated system to classify the severity of hypoxic-ischemic encephalopathy (HIE) in neonates using EEG. A cross disciplinary method is applied that uses the sequences of short-term features of EEG to grade an hour long recording. Novel post-processing techniques are proposed based on majority voting and probabilistic methods. The proposed system is validated with one-hour-long EEG recordings from 54 full term neonates. An overall accuracy of 87% is achieved. The developed grading system has improved both the accuracy and the confidence/quality of the produced decision. With a new label 'unknown' assigned to the recordings with lower confidence levels an accuracy of 96% is attained. The statistical long-term model based features extracted from the sequences of short-term features has improved the overall accuracy of grading the HIE injury in neonatal EEG. The proposed automated HIE grading system can provide significant assistance to healthcare professionals in assessing the severity of HIE. This represents a practical and user friendly implementation which acts as a decision support system in the clinical environment. Its integration with other EEG analysis algorithms may improve neonatal neurocritical care. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
    Full-text · Article · Jun 2015 · Clinical neurophysiology: official journal of the International Federation of Clinical Neurophysiology
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    • "Seetha Shankaran then led the first wholebody cooling (WBC) trial (NICHD) using a cooling blanket, with a target oesophageal temperature of 33.5 C [10]. Later, the TOBY trial led by Denis Azzopardi also applied WBC [11], which since 2007 has become the preferred cooling method. There is no evidence that either method is better. "
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    ABSTRACT: Three ongoing challenges have arisen after the introduction of therapeutic hypothermia (TH) as standard of care for term newborns with moderate or severe perinatal asphyxia: (i) to ensure that the correct group of infants are cooled; (ii) to optimize the delivery of TH and intensive care in relation to the severity of the encephalopathy; (iii) to systematically follow up the long-term efficacy of TH using comparable outcome data between centers and countries. This review addresses the entry criteria for TH, and discusses potential issues regarding patient selection, and management of TH: cooling mild, moderate, and very severe perinatal asphyxia, cooling longer or deeper, and/or starting with a greater delay. This includes cooling of patients outside of standard trial entry criteria, such as after postnatal collapse, premature infants, those with infection, and infants with metabolic, chromosomal or surgical diagnoses in addition to perinatal asphyxia. Copyright © 2015. Published by Elsevier Ltd.
    Full-text · Article · Feb 2015 · Seminars in Fetal and Neonatal Medicine
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