Systemic Hypothermia Induced within 10 Hours After Birth Improved Neurological Outcome in Newborns with Hypoxic-Ischemic Encephalopathy

Li, Tongchuan; Xu, Fanxing; Xiao, Cheng; Guo, Xiaoyan; Ji, Ling; Zhang, Zhan; Wang, Xiaoyang; Blomgren, Klas; Simbruner, G; Zhu, Changlian

doi:10.3810/hp.2009.12.269

Cited by 38 publications

(34 citation statements)

References 22 publications

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“…7 A number of smaller studies reported data consistent with the large pragmatic trials. 17-22 Preliminary information from the Cool Cap trial shows favorable outcome in survivors of HIE at 18 months is highly associated with favorable functional outcome at 7-8 years. 23 The NICHD Whole Body Cooling trial shows that the beneficial effects of hypothermia for neonatal HIE noted at 18 months persist to childhood.…”

Section: Clinical Trials Of Hypothermic Neural Rescuementioning

confidence: 99%

See 1 more Smart Citation

Hypothermia and Other Treatment Options for Neonatal Encephalopathy: An Executive Summary of the Eunice Kennedy Shriver NICHD Workshop

Higgins¹,

Raju²,

Edwards³

et al. 2011

The Journal of Pediatrics

201

138

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Section: Clinical Trials Of Hypothermic Neural Rescuementioning

confidence: 99%

“…4142 There are recent report indicating a significant portion of infants (13 and 18%) cooled beyond the 6 hour of age tested i the randomized trials 43,44 and limited data supporting the potential benefit from such delayecoling. 22 …”

Section: Further Research Into Hypothermic Neural Rescuementioning

confidence: 99%

Hypothermia and Other Treatment Options for Neonatal Encephalopathy: An Executive Summary of the Eunice Kennedy Shriver NICHD Workshop

Higgins¹,

Raju²,

Edwards³

et al. 2011

The Journal of Pediatrics

201

138

View full text Add to dashboard Cite

“…Extensive experimental and clinical research has been carried out into prolonged moderate hypothermia for perinatal asphyxial encephalopathy [2]–[9]. Synthesis of the results of randomised controlled trials show that the number needed to treat (NNT) with cooling to prevent one additional death or disabled survivor is 7, 95% confidence interval (CI) 4–14.…”

Section: Introductionmentioning

confidence: 99%

Implementation and Conduct of Therapeutic Hypothermia for Perinatal Asphyxial Encephalopathy in the UK – Analysis of National Data

et al. 2012

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Background Delay in implementing new treatments into clinical practice results in considerable health and economic opportunity costs. Data from the UK TOBY Cooling Register provides the opportunity to examine how one new effective therapy for newborn infants suspected of suffering asphyxial encephalopathy – therapeutic hypothermia- was implemented in the UK. Methodology/Principal Findings We analysed returned data forms from inception of the Register in December 2006 to the end of July 2011. Data forms were received for 1384 (67%) of the 2069 infants registered. The monthly rate of notifications increased from median {IQR} 18 {15–31} to 33 {30–39} after the announcement of the results of the recent TOBY trial, and to 50 {36–55} after their publication. This rate further increased to 70 {64–83} following official endorsement of the therapy, and is now close to the expected numbers of eligible infants. Cooling was started at 3.3 {1.5–5.5} hours after birth and the time taken to achieve the target 33–34°C rectal temperature was 1 {0–3} hours. The rectal temperature was in the target range in 83% of measurements. From 2006 to 2011 there was evidence of extension of treatment to slightly less severely affected infants. 278 of 1362 (20%) infants died at 2.9 {1.4–4.1} days of age. The rates of death fell slightly over the period of the Register and, at two years of age cerebral palsy was diagnosed in 22% of infants; half of these were spastic bilateral. Factors independently associated with adverse outcome were clinical seizures prior to cooling (p<0.001) and severely abnormal amplitude integrated EEG (p<0.001). Conclusions/Significance Therapeutic hypothermia was implemented appropriately within the UK, with significant benefit to patients and the health economy. This may be due in part to participation by neonatal units in clinical trials, the establishment of the national Register, and its endorsement by advisory bodies.

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“…A significant breakthrough was that post-insult hypothermia within 6 hours reduced severe disability, including cerebral palsy [2]. Other milestones in the field were the findings that low dose rhEPO treatment [3] or delayed hypothermia up to 10 hours [4] reduce the risk of disability in infants with moderate term hypoxic-ischemic encephalopathy. Current therapeutic options for preterm hypoxic-ischemic brain injury are limited and predominantly supportive, to maintain physiological parameters.…”

Section: Introductionmentioning

confidence: 99%

Apoptosis-inducing factor downregulation increased neuronal progenitor, but not stem cell, survival in the neonatal hippocampus after cerebral hypoxia-ischemia

Sun

Zhang

Wang

et al. 2012

Mol Neurodegeneration

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BackgroundA considerable proportion of all newly generated cells in the hippocampus will die before becoming fully differentiated, both under normal and pathological circumstances. The caspase-independent apoptosis-inducing factor (AIF) has not been investigated previously in this context.ResultsPostnatal day 8 (P8) harlequin (Hq) mutant mice, expressing lower levels of AIF, and wild type littermates were injected with BrdU once daily for two days to label newborn cells. On P10 mice were subjected to hypoxia-ischemia (HI) and their brains were analyzed 4 h, 24 h or 4 weeks later. Overall tissue loss was 63.5% lower in Hq mice 4 weeks after HI. Short-term survival (4 h and 24 h) of labeled cells in the subgranular zone was neither affected by AIF downregulation, nor by HI. Long-term (4 weeks) survival of undifferentiated, BLBP-positive stem cells was reduced by half after HI, but this was not changed by AIF downregulation. Neurogenesis, however, as judged by BrdU/NeuN double labeling, was reduced by half after HI in wild type mice but preserved in Hq mice, indicating that primarily neural progenitors and neurons were protected. A wave of cell death started early after HI in the innermost layers of the granule cell layer (GCL) and moved outward, such that 24 h after HI dying cells could be detected in the entire GCL.ConclusionsThese findings demonstrate that AIF downregulation provides not only long-term overall neuroprotection after HI, but also protects neural progenitor cells, thereby rescuing hippocampal neurogenesis.

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Systemic Hypothermia Induced within 10 Hours After Birth Improved Neurological Outcome in Newborns with Hypoxic-Ischemic Encephalopathy

Cited by 38 publications

References 22 publications

Hypothermia and Other Treatment Options for Neonatal Encephalopathy: An Executive Summary of the Eunice Kennedy Shriver NICHD Workshop

Hypothermia and Other Treatment Options for Neonatal Encephalopathy: An Executive Summary of the Eunice Kennedy Shriver NICHD Workshop

Implementation and Conduct of Therapeutic Hypothermia for Perinatal Asphyxial Encephalopathy in the UK – Analysis of National Data

Apoptosis-inducing factor downregulation increased neuronal progenitor, but not stem cell, survival in the neonatal hippocampus after cerebral hypoxia-ischemia

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