Original Article
Moderate Hypothermia to Treat Perinatal Asphyxial Encephalopathy
N Engl J Med 2009; 361:1349-1358October 1, 2009
- Abstract
Background
Whether hypothermic therapy improves neurodevelopmental outcomes in newborn infants with asphyxial encephalopathy is uncertain.
Methods
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°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.
Results
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.
Conclusions
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.)
Media in This Article
Figure 1
Enrollment and Follow-up of the Study Infants.Figure 2
Mean Rectal Temperatures during the Study, According to Treatment Group.Article Activity
- Article
Perinatal asphyxial encephalopathy is associated with high morbidity and mortality rates worldwide and is a major burden for the patient, the family, and society. There is an urgent need to improve outcomes in affected infants.
Experimentally, reducing body temperature to 3 to 5°C below the normal level reduces cerebral injury and improves neurologic function after asphyxia.1-6 Preliminary clinical studies have found no serious adverse effects of cooling.7-9 Two randomized, controlled trials, the CoolCap trial10 and the National Institute of Child Health and Human Development (NICHD) trial,11 have reported outcomes among infants at 18 months of age who had asphyxial encephalopathy, after slightly different cooling regimens. Only the NICHD trial showed a significant reduction in the composite primary outcome of death or disability with hypothermia. Neither trial had sufficient power to detect significant differences in important individual neurologic outcomes, and several systematic reviews and an expert workshop did not reach a consensus in recommending hypothermia as standard treatment.12-17
To clarify the role of hypothermia, we carried out the Total Body Hypothermia for Neonatal Encephalopathy Trial (TOBY), a multicenter, randomized trial comparing intensive care plus total-body cooling for 72 hours with intensive care without cooling among term infants with asphyxial encephalopathy.
Methods
The TOBY protocol was approved by the London Multicenter Research Ethics Committee and the local research ethics committee of each participating hospital. Conduct of the study was overseen by an independent trial steering committee with advice from an independent data monitoring and ethics committee.
Study Design and Procedures
TOBY was a randomized, controlled trial, involving term infants, comparing intensive care plus total-body cooling for 72 hours with intensive care without cooling. Infants were eligible if they were born at or after 36 completed weeks' gestation. They also had to have, at 10 minutes after birth, either an Apgar score of 5 or less or a continued need for resuscitation or, within 60 minutes after birth, acidosis (defined as any occurrence of umbilical-cord, arterial, or capillary pH of <7.00 or base deficit of ≥16 mmol per liter). In addition, they had to have moderate-to-severe encephalopathy (indicated by lethargy, stupor, or coma) and either hypotonia, abnormal reflexes (including oculomotor or pupillary abnormalities), an absent or weak suck, or clinical seizures. Finally, they had to have abnormal background activity of at least 30 minutes' duration or seizures on amplitude-integrated electroencephalography.18
We excluded infants expected to be more than 6 hours of age at the time of randomization and those with major congenital abnormalities known at randomization that required surgery or were suggestive of chromosomal anomaly or syndromes that involve brain dysgenesis.
Written informed consent was obtained from a parent of each infant after explanation of the study, and consent was reaffirmed within the subsequent 24 hours.19 Assignment to a treatment group was performed by means of central telephone randomization or a secure Web-based system (provided by the National Perinatal Epidemiology Unit Clinical Trials Unit, Oxford, United Kingdom). Minimization was used to ensure balance of treatment assignment among infants with various grades of abnormality on amplitude-integrated electroencephalography and within each participating center.
Clinical Management
All recruited infants were cared for in participating centers. Infants from referring hospitals were assessed by trained retrieval teams who performed amplitude-integrated electroencephalography, sought consent if the infant was eligible, performed randomization, and for infants assigned to the cooled group, began cooling by discontinuing warming and applying cooled gel packs, if necessary, until the infant was admitted to a participating center.
To minimize potential confounding from differential use of cointerventions, uniform guidance was provided on ventilatory and circulatory care, management of seizures, sedation, and fluid requirements. All infants underwent sedation with morphine infusions or with chloral hydrate if they appeared to be distressed. Skin temperature and rectal temperature (measured at least 2 cm within the rectum) were monitored continuously and recorded hourly in all infants throughout the intervention period. Clinical staff were made aware of the treatment assignments so that they could manage cooling appropriately.
Intensive Care Alone
Infants assigned to the noncooled group received the current standard of care and were placed under radiant heaters or in incubators, which were servo-controlled according to the abdominal skin temperature to maintain the rectal temperature at 37.0±0.2°C.
Intensive Care with Cooling
Infants assigned to the cooled group were treated in incubators with the power turned off. Hypothermia was maintained by nursing the infant on a cooling blanket in which fluid whose temperature was regulated by a manually adjusted thermostat (Tecotherm TS 200, Tec-Com) was circulated. The target rectal temperature was 33 to 34°C, and typically, the thermostat was set from 25 to 30°C.
Rewarming Procedures
When the period of cooling concluded, 72 hours after randomization, the rectal temperature was monitored for at least 4 hours to prevent rebound hyperthermia. The rectal temperature was allowed to rise by no more than 0.5°C per hour, to a maximum of 37±0.2°C. Cranial ultrasonography was performed daily for the first 4 days after birth, and magnetic resonance imaging (MRI) was conducted, according to a specified protocol, within 5 to 14 days after birth.
Outcomes
The primary outcome at 18 months of age was a composite of death or severe neurodevelopmental disability in survivors. Severe neurodevelopmental disability was defined as a score of less than 70 on the Mental Developmental Index of the Bayley Scales of Infant Development II (BSID-II) (on which the standardization mean [±SD] is 100±15 and higher scores indicate better performance), a score of 3 to 5 on the Gross Motor Function Classification System20 (GMFCS) (on which scores can range from 1 to 5, with higher scores indicating greater impairment), or bilateral cortical visual impairment with no useful vision.
Adverse outcomes included intracranial hemorrhage, persistent hypotension, pulmonary hemorrhage, pulmonary hypertension, prolonged blood coagulation time, culture-proven sepsis, necrotizing enterocolitis, cardiac arrhythmia, thrombocytopenia, major venous thrombosis, renal failure treated with dialysis, pneumonia, pulmonary air leak, and duration of hospitalization. (Most outcomes are defined in the Supplementary Appendix, available with the full text of this article at NEJM.org.)
Secondary outcomes at 18 months, specified before data analysis, included death and severe neurodevelopmental disability (components of the composite primary outcome), the score on the Psychomotor Developmental Index of BSID-II (on which the standardization mean [±SD] is 100±15 and higher scores indicate better performance), cerebral palsy, hearing loss, seizures treated with anticonvulsant agents, microcephaly (i.e., age- and sex-standardized head circumference of more than 2 SD below the mean), multiple neurodevelopmental abnormalities (i.e., more than one of the following: a GMFCS score of 3 to 5, a score of <70 on the Mental Developmental Index of BSID-II) (on which the standardization mean [±SD] is 100±15 and higher scores indicate better performance, seizures, or cortical visual impairment and hearing loss), and survival without neurologic abnormality (i.e., a Mental Developmental Index score >84, a Psychomotor Developmental Index score >84, no abnormalities on GMFCS assessment, and normal vision and hearing).
Neurologic Assessment
Infants were assessed at approximately 18 months of age, through a structured examination by one of five trained assessors who were unaware of the treatment assignments. Neurologic signs and function were scored,20,21 and the presence and type of cerebral palsy were determined. Neurodevelopmental outcome was assessed according to the BSID-II.22
Statistical Analysis
We estimated that a sample of 236 infants would be required to detect a relative risk of 0.6 to 0.7 for the primary outcome in the cooled group as compared with the noncooled group, with a statistical power of 80%, at a two-sided significance level of 5% and assuming a 10% loss to follow-up. This sample size was achieved ahead of schedule, and enrollment was continued after the CoolCap and NICHD trial results suggested that a larger sample would be valuable.
Demographic and clinical characteristics were summarized at baseline as counts and percentages of the total numbers of infants for categorical variables, as means (±SD) for normally distributed continuous variables, and as medians and ranges or interquartile ranges for other continuous variables.
Data were analyzed in the groups to which patients had been assigned regardless of either deviation from the protocol or treatment received. Consistent with previous reports,10,11 neurologic outcomes are presented for survivors who had available follow-up data.
Comparative statistical analysis entailed calculating the relative risks plus the 95% confidence intervals for all dichotomous outcomes, the mean differences plus 95% confidence intervals for normally distributed, continuous outcomes (using analysis of covariance where appropriate), and the median differences plus 95% confidence intervals for skewed continuous variables. In addition, ordered categorical variables were examined with the use of the chi-square test for trend. An adjusted analysis of the primary outcome was performed to investigate the effect of known prognostic factors. All statistical tests were two-sided and were not adjusted for multiple comparisons.
Prespecified subgroup analyses were performed with stratification on the basis of the grade of abnormality on amplitude-integrated electroencephalography at randomization and duration of the interval between birth and randomization (0 to <4 hours vs. 4 to 6 hours). The consistency of the effect of the treatment group across subgroups was explored by means of the statistical test of interaction.
Results
From December 1, 2002, through November 30, 2006, 494 infants were screened and 325 were recruited from 42 hospitals (Figure 1Figure 1
Enrollment and Follow-up of the Study Infants.). The infants were from the United Kingdom (277), Hungary (24), Sweden (18), Israel (4), and Finland (2). Baseline characteristics of the infants (including maternal characteristics) were broadly similar between the two groups (Table 1Table 1
Baseline Characteristics of the Infants.).Compliance with Cooling Protocol
Rectal temperatures were similar between the two groups at the time of randomization (Table 1). Mean rectal temperatures at 6 to 72 hours after randomization were 33.5±0.5°C and 36.9±0.6°C in the cooled and noncooled groups, respectively (Figure 2Figure 2
Mean Rectal Temperatures during the Study, According to Treatment Group.). Among the 162 infants who were not cooled, during the treatment period the temperature rose above 38°C on one occasion in 14 (9%) and on more than one occasion in 23 (14%).Primary Outcome
In the cooled group, 42 infants died and 32 survived with severe neurodevelopmental disability, whereas in the noncooled group, 44 infants died and 42 had severe disability (Table 2Table 2
Main Neurodevelopmental Outcomes at 18 Months.) (relative risk for either outcome, 0.86; 95% confidence interval [CI], 0.68 to 1.07; P=0.17). The result was materially unchanged when adjusted for severity of abnormality on amplitude-integrated electroencephalography, sex, or age at randomization.Adverse Outcomes
The incidence of adverse events was similar in the two groups (Table 3Table 3
Adverse Outcomes, According to Treatment Group.). Hypotension, thrombocytopenia, prolonged coagulation time, and intracranial hemorrhage (seen only on MRI) were frequently observed in both groups. Serious adverse events other than death were uncommon and were not associated with cooling. Two infants in the cooled group and one in the noncooled group had sinus thrombosis noted on MRI. Another infant in the cooled group had a thrombus in the aorta, as well as an umbilical arterial catheter and a hematocrit of 70%. No case of renal failure requiring dialysis occurred.Secondary Outcomes at 18 Months
The mortality rate was similar in both groups. Forty-two infants in the cooled group died, as did 44 infants in the noncooled group; in each group, 39 of those died before hospital discharge. Death occurred after the withdrawal of care in 34 of the 39 (87%) in the cooled group and 29 of the 39 (74%) in the noncooled group.
Outcomes were significantly improved in the cooled group with regard to 5 of the 12 secondary neurologic outcomes assessed (Table 2). The rate of survival without a neurologic abnormality was significantly increased in the cooled group (71 of 163 infants [44%], vs. 45 of 162 [28%] in the noncooled group; 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 abnormal GMFCS score (relative risk, 0.63; 95% CI, 0.45 to 0.89; P=0.007) and resulted in improvements in the Mental Developmental Index and Psychomotor Developmental Index scores (P=0.03 for each), and the GMFCS score (P=0.01). The rate of multiple neurodevelopmental abnormalities was 21 of 112 in the cooled group, as compared with 33 of 110 in the noncooled group (relative risk, 0.63; 95% CI, 0.39 to 1.01; P=0.05). Results from the complete analysis of the neurodevelopmental assessments are provided in the Supplementary Appendix.
Subgroup Analyses
More infants with severely abnormal results on amplitude-integrated electroencephalography at the time of randomization died or had a severe disability than did those with moderately abnormal results (109 of 193 [56%] vs. 50 of 132 [38%]; relative risk, 1.49; 95% CI, 1.16 to 1.91; P=0.001). However, the effect of cooling did not significantly vary according to the severity of abnormality on amplitude-integrated electroencephalography (P=0.23 for interaction). The results were similar when the analysis was carried out with the results of amplitude-integrated electroencephalography classified as in the CoolCap study.10 The effect of treatment group did not vary significantly on the basis of time to randomization: among the 105 infants randomly assigned to a group less than 4 hours after birth, the relative risk for the primary outcome with cooling was 0.77 (95% CI, 0.44 to 1.04), whereas among the 220 remaining infants who were randomly assigned between 4 and 6 hours after birth, the relative risk was 0.95 (95% CI, 0.72 to 1.25; P=0.21 for interaction).
Discussion
In this trial of near-term infants with perinatal asphyxia, we found no significant difference in the risk of the primary outcome, the combined rates of death or severe disability, between the cooled group and the noncooled group. However, cooling resulted in consistent improvement in secondary outcomes, including a significant increase in the rate of survival without neurologic abnormalities and improved neurodevelopmental outcomes among survivors.
The primary outcome of TOBY, as in the CoolCap and NICHD trials, was a composite end point, chosen because of concerns that cooling might increase survival with additional disability. Results of all three trials are consistent with respect to this primary outcome, with point estimates supporting a benefit from hypothermia: the relative risk associated with cooling (vs. no cooling) was 0.82 (95% CI, 0.66 to 1.02) in the CoolCap study, 0.72 (95% CI, 0.71 to 0.93) in the NICHD trial (which included infants with moderate disability), and 0.86 (95% CI, 0.68 to 1.07) in the present trial.
Our categorization of neurologic outcomes is consistent with that used in the CoolCap and NICHD trials and previous systematic reviews,12-17 facilitating the comparison of our findings with previous results. We found a significant increase in the rate of survival without neurologic abnormality with cooling (relative risk, 1.57; 95% CI, 1.16 to 2.12); the NICHD and CoolCap trials, which were smaller than the present trial, showed nonsignificant benefits with regard to this outcome but had similar point estimates. The relative risk in the NICHD trial was 1.51 (95% CI, 0.94 to 2.42),23 and the relative risk in the CoolCap trial was 1.48 (95% CI, 0.89 to 2.45) (Gunn A, University of Auckland, New Zealand: personal communication).
Although there is striking homogeneity among results of these three trials, there are also some differences. Only the NICHD trial detected a significant effect of hypothermia on the primary outcome, and only TOBY detected significant improvements in specific neurologic outcomes. Both TOBY and the CoolCap trial showed that the increased risk of death or severe disability in infants with the most abnormal grade on amplitude-integrated electroencephalography was unaffected by cooling, but the CoolCap results suggested a reduction of the risk in the subgroup with less severely abnormal findings.
These discrepancies among results may be explained in part by differences in the trial protocols. In all three trials, the whole-body temperature (as measured in the rectum or esophagus) was reduced, but the strategies for cooling and the target temperatures varied: temperature was decreased to 33 to 34°C with the use of cooling blankets in TOBY and the NICHD trial and to 34 to 35°C by means of scalp cooling in the CoolCap study. The NICHD trial recorded slightly higher temperatures in the control group than did the other two trials. In TOBY, but not the other two trials, cooling was initiated during transport to the treatment center. In TOBY and the CoolCap trial, but not the NICHD trial, patients were selected on the basis of the presence of abnormalities on amplitude-integrated electroencephalography in addition to clinical criteria. Differences in local practices for withdrawal of care may also have affected outcomes. Withdrawal was slightly more common in the control group than in the cooled group in the NICHD study but was more common in the cooled group than in the control group in TOBY; these results may partially account for the greater apparent effect of hypothermia on mortality rate in the NICHD study as compared with TOBY.
Elevation of body temperature to greater than 38°C was observed in several noncooled infants in the NICHD and CoolCap trials and was associated with a worse outcome in the CoolCap trial.11,24 A rectal temperature of more than 38°C was also noted in some noncooled infants in TOBY. Experimental data showing that pyrexia may adversely affect neurodevelopment support the possibility that increased temperatures may contribute to the poorer outcomes seen in the noncooled groups; however, it is also possible that the relationship between higher elevation of body temperature and poor outcome reflects reverse causation (i.e., asphyxia resulting in impairment of temperature regulation).
Consistent with findings in the earlier trials, in our study, minor respiratory and cardiovascular events were common, but serious adverse events were rare and were not associated with cooling. Mild-to-moderate intracranial hemorrhage that was not visible on cranial ultrasonography was frequently seen on MRI in both groups, and sinus thrombosis occurred very infrequently in both groups.
No trial, to our knowledge, has yet reported neurologic outcomes at ages older than 18 months. Neurodevelopmental assessments at 18 months may not reliably predict later outcomes.25 Although it is likely that severe neuromotor disability will have been correctly identified at 18 months, less severe impairments are not reliably assessable at this age. Assessment later in childhood (e.g., at 6 to 7 years of age) is necessary for accurate, comprehensive evaluation of cognitive function, behavior and learning, fine motor development, attention, and psychosocial health.26
In conclusion, TOBY did not show a significant reduction in the combined rates of death and severe disability with cooling, as compared with no cooling, but did show a significant improvement in several secondary neurologic outcomes among survivors. Whether this improvement is maintained in the longer term needs to be ascertained.
Supported by grants from the U.K. Medical Research Council and the U.K. Department of Health.
No potential conflict of interest relevant to this article was reported.
We thank the Imperial College Healthcare Biomedical Research Centre and Bliss, the Special Care Baby Charity, for their advice and support, as well as all the parents and infants who took part in the study.
Source Information
From the Division of Clinical Sciences and Medical Research Council (MRC) Clinical Sciences Centre, Hammersmith Hospital, Imperial College London, London (D.V.A., A.D.E., L.D., O.K., E.P.); the National Perinatal Epidemiology Unit, University of Oxford, Oxford (B.S., E.J., P.B.); the Department of Perinatal Medicine, Royal Maternity Hospital and Department of Child Health, Queen's University, Belfast (H.L.H.); the University of Leeds and Leeds General Infirmary, Leeds (M.L.); the Academic Division of Child Health, Queen's Medical Centre, Nottingham (N.M.); and the Department of Clinical Science, University of Bristol, St. Michael's Hospital (M.T.) and Southmead Hospital (A.W.), Bristol — all in the United Kingdom.
Address reprint requests to Dr. Azzopardi at the Division of Clinical Sciences and MRC Clinical Sciences Centre, Imperial College London, Hammersmith Hospital, Du Cane Rd., London W12 0NN, United Kingdom, or at d.azzopardi@imperial.ac.uk.
The members of the Total Body Hypothermia for Neonatal Encephalopathy Trial (TOBY) study group are listed in the Appendix.
Appendix
Members of the TOBY Study Group are as follows: Project Management Group — D. Azzopardi (chief investigator), P. Brocklehurst (chief investigator), A.D. Edwards (principal investigator), H. Halliday (principal investigator), M. Levene (principal investigator), M. Thoresen (principal investigator), A. Whitelaw (principal investigator), S. Ayers (National Perinatal Epidemiology Unit [NPEU] information technology coordinator), U. Bowler (NPEU Clinical Trials Unit [CTU] senior trials manager), M. Gallagher (NPEU data manager), E. Juszczak (NPEU CTU head of trials), C. Mulhall (NPEU TOBY study coordinator), B. Strohm (NPEU TOBY research nurse and study coordinator); Writing Committee — D. Azzopardi (chief investigator), P. Brocklehurst (chief investigator), A.D. Edwards (principal investigator), E. Juszczak (NPEU CTU head of trials); Trial Steering Committee — N. McIntosh (chair), Child Life and Health, University of Edinburgh, Edinburgh, United Kingdom (UK); D. Azzopardi, Imperial College London, London; H. Baumer, Derriford Hospital, Plymouth, UK; P. Brocklehurst, NPEU, University of Oxford, Oxford, UK; C. Doré, Medical Research Council (MRC) CTU; D. Elbourne, London School of Hygiene and Tropical Medicine, London; R. Parnell, Scope Data Monitoring and Ethics Committee; R. Cooke (chair), Liverpool Women's Hospital, University of Liverpool, Liverpool, UK; H. Davies, National Research Ethics Service; A. Johnson, University of Oxford, Oxford, UK; S. Richmond, Sunderland District General Hospital, University of Newcastle, Newcastle, UK; P. Yudkin, Division of Public Health and Primary Health Care, University of Oxford, Oxford, UK; Trial Statisticians (NPEU) — S. Gates, Edmund Juszczak, M. Quigley; Trial Health Economists (NPEU) — O. Eddama, J. Henderson, S. Petrou; Clinical Research Fellow — O. Kapellou; Follow-up Pediatricians — L. Dyet, E. Porter, Imperial College London, London; G. Mero, Jósa András County Hospital, Nyíregyháza, Hungary; B. Vollmer, Karolinska Institutet, Stockholm; E. Goldstein, Soroka Medical Center, Beersheeva, Israel; Specialist Adviser — B. Hutchon, Royal Free Hospital, London; Cranial Ultrasonography Interpretation — C. Hagmann, University College London, London; Bayley Scales of Infant Development II (BSID-II) Training — S. Johnson, University of Nottingham, Nottingham, UK; MRI Evaluation — L. Ramenghi, University of Milan, Milan; M. Rutherford, MRC Clinical Sciences Centre, Imperial College London, London; Centers for Recruitment and Data Collection for MRI Evaluation (in descending order of no. of infants recruited, in parentheses) — Hammersmith Hospital, London (54) — D. Azzopardi, A.D. Edwards, O. Kapellou, P. Corcoran; First Department of Pediatrics, Semmelweis University Hospital, Budapest, Hungary (24) — M. Szabó, A. Róka, E. Bodrogi; Homerton Hospital, London (20) — E. Maalouf, C. Harris; Southmead Hospital, Bristol, UK (20) — A. Whitelaw, S. Lamburne; University College Hospital, London (19) — N. Robertson, A. Kapetanakis; St. George's Hospital, London (18) — K. Farrer, L. Kay-Smith; Royal Maternity Hospital, Belfast, UK (17) — H. Halliday, D. Sweet; Liverpool Women's Hospital, Liverpool, UK (15) — M. Weindling, A.S. Burke; St. Michael's Hospital, Bristol, UK (14) — M. Thoresen, J. Tooley, J. Kemp; Leicester Royal Infirmary, Leicester, UK (12) — A. Currie, M. Hubbard; Royal Sussex County Hospital, Brighton, UK (10) — P. Amess; Queen Silvia's Hospital, Gothenburg, Sweden (9) — K. Thiringer, A. Flisberg; Leeds General Infirmary, Leeds, UK (8) — M. Levene, A. Harrop; Nottingham City Hospital, Nottingham, UK (8) — S. Watkin, D. Jayasinghe; John Radcliffe Hospital, Oxford, UK (7) — E. Adams; Karolinska Institutet, Stockholm (6) — C. Lothian, M. Blennow; Medway Maritime Hospital, Gillingham, UK (6) — S. Rahman, B. Jani, K. Vandertak; Luton and Dunstable Hospital, Luton, UK (5) — S. Skinner, Y. Millar; Queen's Medical Centre, Nottingham, UK (5) — N. Marlow, S. Wardle; Jessop Wing, Sheffield, UK (4) — M. Smith; Royal Victoria Infirmary, Newcastle, UK (4) — J. Berrington; Soroka Medical Center, Beersheva, Israel (4) — K. Marks; Bradford Royal Infirmary, Bradford, UK (3) — S. Chatfield; Heartlands Hospital, Birmingham, UK (3) — S. Rose; New Cross Hospital, Wolverhampton, UK (3) — B. Kumararatne, L. Greig; Norfolk and Norwich University Hospital, Norwich, UK (3) — P. Clarke; Lund University Hospital, Lund, Sweden (3) — V. Fellman; Wishaw General Hospital, Wishaw, UK (3) — R. Abara; City Hospital, Birmingham, UK (2) — D. Armstrong; Erinville Hospital–Cork University Hospital, Cork, Ireland (2) — D. Murray; Hospital for Children and Adolescents, Helsinki (2) — M. Metsaranta; Queen Mother's Hospital, Glasgow, UK (2) — J. Simpson; Singleton Hospital, Swansea, UK (2) — J. Matthes; Southern General Hospital, Glasgow, UK (2) — P. MacDonald; University Hospital of Wales, Cardiff, UK (2) — S. Cherian; Princess Royal Maternity Hospital, Glasgow, UK (1) — L. Jackson; Royal Cornwall Hospital, Truro, UK (1) — P. Munyard; Royal Devon and Exeter Foundation Trust, Exeter, UK (1) — M. Quinn; St. Mary's Hospital, Manchester, UK (1) — S. Mitchell; James Cook University Hospital, Middlesbrough, UK (0) — S. Sinha; Derriford Hospital, Plymouth, UK (0) — J. Eason; Department of Pediatrics, Oulu University Hospital, Oulu, Finland (0) — M. Hallman.
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- Citing Articles (175)
Citing Articles
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Elavazhagan Chakkarapani, Marianne Thoresen, Xun Liu, Lars Walloe, John Dingley. (2012) Xenon offers stable haemodynamics independent of induced hypothermia after hypoxia–ischaemia in newborn pigs. Intensive Care Medicine 38:2, 316-323
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Rainer Kollmar, Stefan Schwab. (2012) Hypothermia and Ischemic Stroke. Current Treatment Options in Neurology
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Toshiki Takenouchi, Osuke Iwata, Makoto Nabetani, Masanori Tamura. (2012) Therapeutic hypothermia for neonatal encephalopathy: JSPNM & MHLW Japan Working Group Practice Guidelines. Brain and Development 34:2, 165-170
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Niamh E. Lynch, Nathan J. Stevenson, Vicki Livingstone, Brendan P. Murphy, Janet M. Rennie, Geraldine B. Boylan. (2012) The temporal evolution of electrographic seizure burden in neonatal hypoxic ischemic encephalopathy. Epilepsiano-no
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Sara Paterson-Brown. 2012. Fetal Monitoring during Labour. , 326-337.
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Li Wu, Bin Yi, Yang Hu, Cunwei Ji, Tao Zhang, Youjie Wang. (2012) The Efficacy of Hypothermia in Hypoxic-Ischemic Encephalopathy at 18 Mo or More. The Indian Journal of Pediatrics
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Glynn Russell. 2012. Neonatal Care for Obstetricians. , 377-393.
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Marisol Mirabelli-Badenier, Vincent Braunersreuther, Sébastien Lenglet, Katia Galan, Edvige Veneselli, Giorgio L. Viviani, François Mach, Fabrizio Montecucco. (2012) Pathophysiological role of inflammatory molecules in paediatric ischaemic brain injury. European Journal of Clinical Investigationno-no
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Osuke Iwata, Makoto Nabetani, Toshiki Takenouchi, Takayuki Iwaibara, Sachiko Iwata, Masanori Tamura, . (2012) Hypothermia for neonatal encephalopathy: Nationwide Survey of Clinical Practice in Japan as of August 2010. Acta Paediatricano-no
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Robert D. Christensen, Mark J. Sheffield, Diane K. Lambert, Vickie L. Baer. (2012) Effect of Therapeutic Hypothermia in Neonates with Hypoxic-Ischemic Encephalopathy on Platelet Function. Neonatology 101:2, 91-94
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Marcia Hogeling, Katharine Meddles, David R. Berk, Anna L. Bruckner, Thomas K. Shimotake, Ronald S. Cohen, Ilona J. Frieden. (2012) Extensive Subcutaneous Fat Necrosis of the Newborn Associated with Therapeutic Hypothermia. Pediatric Dermatology 29:1, 59-63
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Seetha Shankaran, Abbot R. Laptook, Scott A. McDonald, Rosemary D. Higgins, Jon E. Tyson, Richard A. Ehrenkranz, Abhik Das, Guilherme SantʼAnna, Ronald N. Goldberg, Rebecca Bara, Michele C. Walsh. (2012) Temperature profile and outcomes of neonates undergoing whole body hypothermia for neonatal hypoxic-ischemic encephalopathy. Pediatric Critical Care Medicine 13:1, 53-59
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Sonia L. Bonifacio, Fernando Gonzalez, Donna M. Ferriero. 2012. Central Nervous System Injury and Neuroprotection. , 869-891.
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George A. Woodward, Roxanne Kirsch, Michael Stone Trautman, Monica E. Kleinman, Gil Wernovsky, Bradley S. Marino. 2012. Stabilization and Transport of the High-Risk Infant. , 341-356.
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Mary Leppert, Marilee C. Allen. 2012. Risk Assessment and Neurodevelopmental Outcomes. , 920-935.
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Tina A. Leone, Neil N. Finer. 2012. Resuscitation in the Delivery Room. , 328-340.
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Nicholas S. Abend, Alexis A. Topjian, Sudha Kilaru Kessler, Ana M. Gutierrez-Colina, Robert A. Berg, Vinay Nadkarni, Dennis J. Dlugos, Robert R. Clancy, Rebecca N. Ichord. (2012) Outcome prediction by motor and pupillary responses in children treated with therapeutic hypothermia after cardiac arrest*. Pediatric Critical Care Medicine 13:1, 32-38
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Cédric Delhaye, Michael Mahmoudi, Ron Waksman. (2012) Hypothermia Therapy. Journal of the American College of Cardiology 59:3, 197-210
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Niranjan Thomas, Sridhar Santhanam, Manish Kumar, Kurien Anil Kuruvilla, Atanu Kumar Jana. (2012) Hypothermia for neonatal encephalopathy in resource-poor environments. The Journal of Pediatrics
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Lucia Rivera-Lara, Jiaying Zhang, Susanne Muehlschlegel. (2011) Therapeutic Hypothermia for Acute Neurological Injuries. Neurotherapeutics
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Hannah C. Glass, Sonia L. Bonifacio, Thomas Shimotake, Donna M. Ferriero. (2011) Neurocritical Care for Neonates. Current Treatment Options in Neurology 13:6, 574-589
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P. Wintermark, A. Hansen, M. C. Gregas, J. Soul, M. Labrecque, R. L. Robertson, S. K. Warfield. (2011) Brain Perfusion in Asphyxiated Newborns Treated with Therapeutic Hypothermia. American Journal of Neuroradiology 32:11, 2023-2029
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E. Lopez. (2011) Prise en charge pédiatrique du nouveau-né post-terme. Journal de Gynécologie Obstétrique et Biologie de la Reproduction 40:8, 812-817
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Siri St. Llaurent Kowalski. (2011) The effects of therapeutic hypothermia on term infants with neonatal asphyxial encephalopathy. Journal of Neonatal Nursing 17:6, 197-202
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Oliver Bandschapp, Matthew T. Sweney, Judy A. Miller, Samira Tahvildari, Daniel C. Sigg, Paul A. Iaizzo. (2011) Induction of Mild Hypothermia by Noninvasive Body Cooling in Healthy, Unanesthetized Subjects. Therapeutic Hypothermia and Temperature Management 1:4, 193-198
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Rıdvan Duran, Işık Görker, Yasemin Küçükuğurluoğlu, Nükhet AladağÇiftdemir, Ülfet Vatansever Özbek, Betül Acunaş. (2011) Effect of neonatal resuscitation courses on long-term neurodevelopmental outcomes of newborn infants with perinatal asphyxia. Pediatrics Internationalno-no
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Renée A. Shellhaas, Taeun Chang, Tammy Tsuchida, Mark S. Scher, James J. Riviello, Nicholas S. Abend, Sylvie Nguyen, Courtney J. Wusthoff, Robert R. Clancy. (2011) The American Clinical Neurophysiology Societyʼs Guideline on Continuous Electroencephalography Monitoring in Neonates. Journal of Clinical Neurophysiology 28:6, 611-617
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Barnaby Scholefield, Kevin Morris, Heather Duncan, Paul Davies, Fang Gao Smith, Khalid Khan, Barnaby Scholefield. 2011. Hypothermia for neuroprotection in children after cardiopulmonary arrest. .
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D. Blanco, A. García-Alix, E. Valverde, V. Tenorio, M. Vento, F. Cabañas. (2011) Neuroprotección con hipotermia en el recién nacido con encefalopatía hipóxico-isquémica. Guía de estándares para su aplicación clínica. Anales de Pediatría 75:5, 341.e1-341.e20
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HANNAH C. GLASS, KAREN J. HONG, ELIZABETH E. ROGERS, RITA J. JEREMY, SONIA L. BONIFACIO, JOSEPH E. SULLIVAN, A. JAMES BARKOVICH, DONNA M. FERRIERO. (2011) Risk Factors for Epilepsy in Children With Neonatal Encephalopathy. Pediatric Research 70:5, 535-540
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Denise M. Casey, Nancy Tella, Rachel Turesky, Michelle Labrecque. (2011) Therapeutic Hypothermia: Treatment for Hypoxic-Ischemic Encephalopathy in the NICU. Neonatal Network: The Journal of Neonatal Nursing 30:6, 370-380
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Rosemary D. Higgins, Tonse Raju, A. David Edwards, Denis V. Azzopardi, Carl L. Bose, Reese H. Clark, Donna M. Ferriero, Ronnie Guillet, Alistair J. Gunn, Henrik Hagberg, Deborah Hirtz, Terrie E. Inder, Susan E. Jacobs, Dorothea Jenkins, Sandra Juul, Abbot R. Laptook, Jerold F. Lucey, Mervyn Maze, Charles Palmer, LuAnn Papile, Robert H. Pfister, Nicola J. Robertson, Mary Rutherford, Seetha Shankaran, Faye S. Silverstein, Roger F. Soll, Marianne Thoresen, William F. Walsh. (2011) Hypothermia and Other Treatment Options for Neonatal Encephalopathy: An Executive Summary of the Eunice Kennedy Shriver NICHD Workshop. The Journal of Pediatrics 159:5, 851-858.e1
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A. Avila-Alvarez, I. Gonzalez-Rivera, A. Ferrer-Barba, F. Portela-Torron, E. Gonzalez-Garcia, J.L. Fernandez-Trisac, C. Ramil-Fraga. (2011) Complicaciones neurológicas en el postoperatorio inmediato de cirugía cardiaca: todavía un largo camino por recorrer. Anales de Pediatría
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Hannah C. Glass, Kendall B. Nash, Sonia L. Bonifacio, A. James Barkovich, Donna M. Ferriero, Joseph E. Sullivan, Maria Roberta Cilio. (2011) Seizures and Magnetic Resonance Imaging–Detected Brain Injury in Newborns Cooled for Hypoxic-Ischemic Encephalopathy. The Journal of Pediatrics 159:5, 731-735.e1
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Seetha Shankaran, Abbot R. Laptook, Jon E. Tyson, Richard A. Ehrenkranz, Carla M. Bann, Abhik Das, Rosemary D. Higgins, Rebecca Bara, Athina Pappas, Scott A. McDonald, Ronald N. Goldberg, Michele C. Walsh. (2011) Evolution of Encephalopathy during Whole Body Hypothermia for Neonatal Hypoxic-Ischemic Encephalopathy. The Journal of Pediatrics
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Ylva Carlsson, Leslie Schwendimann, Regina Vontell, Catherine I. Rousset, Xiaoyang Wang, Sophie Lebon, Christiane Charriaut-Marlangue, Veena Supramaniam, Henrik Hagberg, Pierre Gressens, Etienne Jacotot. (2011) Genetic inhibition of caspase-2 reduces hypoxic-ischemic and excitotoxic neonatal brain injury. Annals of Neurology 70:5, 781-789
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Aniko Roka, Dorottya Kelen, Jozsef Halasz, Gabriella Beko, Denis Azzopardi, Miklos Szabo. (2011) Serum S100B and neuron-specific enolase levels in normothermic and hypothermic infants after perinatal asphyxia. Acta Paediatricano-no
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Luc Mertens, Istvan Seri, Jan Marek, Romaine Arlettaz, Piers Barker, Patrick McNamara, Anita J. Moon-Grady, Patrick D. Coon, Shahab Noori, John Simpson, Wyman W. Lai. (2011) Targeted Neonatal Echocardiography in the Neonatal Intensive Care Unit: Practice Guidelines and Recommendations for Training. Journal of the American Society of Echocardiography 24:10, 1057-1078
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Maja Elstad, Andrew Whitelaw, Marianne Thoresen. (2011) Cerebral Resistance Index is less predictive in hypothermic encephalopathic newborns. Acta Paediatrica 100:10, 1344-1349
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Hongfu Li, Qian Li, Xiaonan Du, Yanyan Sun, Xiaoyang Wang, Guido Kroemer, Klas Blomgren, Changlian Zhu. (2011) Lithium-mediated long-term neuroprotection in neonatal rat hypoxia-ischemia is associated with antiinflammatory effects and enhanced proliferation and survival of neural stem/progenitor cells. Journal of Cerebral Blood Flow & Metabolism 31:10, 2106-2115
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L. Mertens, I. Seri, J. Marek, R. Arlettaz, P. Barker, P. McNamara, A. J. Moon-Grady, P. D. Coon, S. Noori, J. Simpson, W. W. Lai, . (2011) Targeted Neonatal Echocardiography in the Neonatal Intensive Care Unit: Practice Guidelines and Recommendations for Training: Writing group of the American Society of Echocardiography (ASE) in collaboration with the European Association of Echocardiography (EAE) and the Association for European Pediatric Cardiologists (AEPC). European Journal of Echocardiography 12:10, 715-736
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Sandra Rees, Richard Harding, David Walker. (2011) The biological basis of injury and neuroprotection in the fetal and neonatal brain. International Journal of Developmental Neuroscience 29:6, 551-563
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Dieter Hüseman, Boris Metze, Elisabeth Walch, Christoph Bührer. (2011) Laboratory markers of perinatal acidosis are poor predictors of neurodevelopmental impairment in very low birth weight infants. Early Human Development 87:10, 677-681
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Pablo Galeano, Eduardo Blanco Calvo, Diêgo Madureira de Oliveira, Lucas Cuenya, Giselle Vanesa Kamenetzky, Alba Elisabeth Mustaca, George Emilio Barreto, Lisandro Diego Giraldez-Alvarez, José Milei, Francisco Capani. (2011) Long-lasting effects of perinatal asphyxia on exploration, memory and incentive downshift. International Journal of Developmental Neuroscience 29:6, 609-619
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Terrie E. Inder. (2011) Pediatrics: Predicting outcomes after perinatal brain injury. Nature Reviews Neurology 7:10, 544-545
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Fenella Kirkham. (2011) Cardiac arrest and post resuscitation of the brain. European Journal of Paediatric Neurology 15:5, 379-389
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Lina F. Chalak, Dwight J. Rouse. (2011) Neuroprotective Approaches: Before and After Delivery. Clinics in Perinatology 38:3, 455-470
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D Chauvier, S Renolleau, S Holifanjaniaina, S Ankri, M Bezault, L Schwendimann, C Rousset, R Casimir, J Hoebeke, M Smirnova, G Debret, A-P Trichet, Y Carlsson, X Wang, E Bernard, M Hébert, J-M Rauzier, S Matecki, A Lacampagne, P Rustin, J Mariani, H Hagberg, P Gressens, C Charriaut-Marlangue, E Jacotot. (2011) Targeting neonatal ischemic brain injury with a pentapeptide-based irreversible caspase inhibitor. Cell Death and Disease 2:9, e203
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Elizabeth M. Moore, Alistair D. Nichol, Stephen A. Bernard, Rinaldo Bellomo. (2011) Therapeutic hypothermia: Benefits, mechanisms and potential clinical applications in neurological, cardiac and kidney injury. Injury 42:9, 843-854
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Katherine M. Newnam, Donna L. DeLoach. (2011) Neonatal Hypothermia: A Method to Provide Neuroprotection After Hypoxic Ischemic Encephalopathy. Newborn and Infant Nursing Reviews 11:3, 113-124
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Javier Vaquero. (2011) Therapeutic hypothermia in the management of acute liver failure. Neurochemistry International
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Thomas A. Nakagawa, Stephen Ashwal, Mudit Mathur, Mohan R. Mysore, Derek Bruce, Edward E. Conway, Susan E. Duthie, Shannon Hamrick, Rick Harrison, Andrea M. Kline, Daniel J. Lebovitz, Maureen A. Madden, Vicki L. Montgomery, Jeffrey M. Perlman, Nancy Rollins, Sam D. Shemie, Amit Vohra, Jacqueline A. Williams-Phillips. (2011) Guidelines for the determination of brain death in infants and children: An update of the 1987 Task Force recommendations*. Critical Care Medicine 39:9, 2139-2155
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Sally Jary, Grazyna Kmita, Andrew Whitelaw. (2011) Differentiating Developmental Outcome between Infants with Severe Disability in Research Studies: The Role of Bayley Developmental Quotients. The Journal of Pediatrics 159:2, 211-214.e1
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Ernest B. Cady, Juliet Penrice, Nicola J. Robertson. (2011) Improved reproducibility of MRS regional brain thermometry by ‘amplitude-weighted combination’. NMR in Biomedicine 24:7, 865-872
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Cora H. Nijboer, Cobi J. Heijnen, Michael A. van der Kooij, Jitske Zijlstra, Cindy T.J. van Velthoven, Carsten Culmsee, Frank van Bel, Henrik Hagberg, Annemieke Kavelaars. (2011) Targeting the p53 pathway to protect the neonatal ischemic brain. Annals of Neurology 70:2, 255-264
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(2011) After the Resuscitation of a Newborn Infant. ARC and NZRC Guideline 2010. Emergency Medicine Australasia 23:4, 448-449
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Kathleen M O’Reilly, James Tooley, Sharon Winterbottom. (2011) Therapeutic hypothermia during neonatal transport. Acta Paediatrica 100:8, 1084-1086
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(2011) Introduction to Resuscitation of the Newborn Infant. ARC and NZRC Guideline 2010. Emergency Medicine Australasia 23:4, 419-423
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Toshiki Takenouchi, Elayna O. Rubens, Vivien L. Yap, Gail Ross, Murray Engel, Jeffrey M. Perlman. (2011) Delayed Onset of Sleep-Wake Cycling with Favorable Outcome in Hypothermic-Treated Neonates with Encephalopathy. The Journal of Pediatrics 159:2, 232-237
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Regina Reynolds, Samara Talmage. (2011) "Caution! Contents Should Be Cold": Developing a Whole-Body Hypothermia Program. Neonatal Network: The Journal of Neonatal Nursing 30:4, 225-230
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Kıvılcım Gucuyener, Serdar Beken, Ebru Ergenekon, Sebnem Soysal, İbrahim Hirfanoglu, Ozden Turan, Sezin Unal, Nilgün Altuntas, Ebru Kazanci, Ferit Kulali, Esin Koc, Canan Turkyilmaz, Esra Onal, Yıldız Atalay. (2011) Use of amplitude-integrated electroencephalography (aEEG) and near infrared spectroscopy findings in neonates with asphyxia during selective head cooling. Brain and Development
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Yoshie Taniguchi, Rainer Lenhardt, Daniel I. Sessler, Andrea Kurz. (2011) The Effect of Altering Skin-Surface Cooling Speeds on Vasoconstriction and Shivering Thresholds. Anesthesia & Analgesia1
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Stuart Faulkner, Alan Bainbridge, Takenori Kato, Manigandan Chandrasekaran, Andrew B. Kapetanakis, Mariya Hristova, Mengyan Liu, Samantha Evans, Enrico De Vita, Dorottya Kelen, Robert D. Sanders, A. David Edwards, Mervyn Maze, Ernest B. Cady, Gennadij Raivich, Nicola J. Robertson. (2011) Xenon augmented hypothermia reduces early lactate/N-acetylaspartate and cell death in perinatal asphyxia. Annals of Neurology 70:1, 133-150
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B.H. Walsh, D.M. Murray, G.B. Boylan. (2011) The use of conventional EEG for the assessment of hypoxic ischaemic encephalopathy in the newborn: A review. Clinical Neurophysiology 122:7, 1284-1294
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Andrea Hobson, Craig Sussman, Jennifer Knight, Joy Perkins, Lily Irwin, Vanessa Larsen, Christine Brophy, Michael D. Weiss. (2011) Active Cooling During Transport of Neonates with Hypoxic-Ischemic Encephalopathy. Air Medical Journal 30:4, 197-200
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CESAR V. BORLONGAN, MICHAEL D. WEISS. (2011) Baby STEPS: A Giant Leap for Cell Therapy in Neonatal Brain Injury. Pediatric Research 70:1, 3-9
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S Zanelli, M Buck, K Fairchild. (2011) Physiologic and pharmacologic considerations for hypothermia therapy in neonates. Journal of Perinatology 31:6, 377-386
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Niranjan Thomas, Koshy C. George, Santhanam Sridhar, Manish Kumar, Kurien Anil Kuruvilla, Atanu Kumar Jana. (2011) Whole body cooling in newborn infants with perinatal asphyxial encephalopathy in a low resource setting: A Feasibility Trial. Indian Pediatrics 48:6, 445-451
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Michael V. Johnston. (2011) Education of a Child Neurologist: Developmental Neuroscience Relevant to Child Neurology. Seminars in Pediatric Neurology 18:2, 133-138
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Joanne Ng, Vijeya Ganesan. (2011) Expert opinion on emerging drugs in childhood arterial ischemic stroke. Expert Opinion on Emerging Drugs 16:2, 363-372
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Oliver Bandschapp, Paul A. Iaizzo. (2011) Induction of Therapeutic Hypothermia Requires Modulation of Thermoregulatory Defenses. Therapeutic Hypothermia and Temperature Management 1:2, 77-85
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A Levick, D Land, J Hand. (2011) Validation of microwave radiometry for measuring the internal temperature profile of human tissue. Measurement Science and Technology 22:6, 065801
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Jong Youl Kim, Nuri Kim, Midori A. Yenari, Wenhan Chang. (2011) Mild Hypothermia Suppresses Calcium-Sensing Receptor (CaSR) Induction Following Forebrain Ischemia While Increasing GABA-B Receptor 1 (GABA-B-R1) Expression. Translational Stroke Research 2:2, 195-201
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N. Deye. (2011) De l’hypothermie thérapeutique au contrôle ciblé de la température: une conférence de consensus sur fond de nombreuses incertitudes. Réanimation 20:3, 159-161
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Elena V. Wachtel, Karen D. Hendricks-Muñoz. (2011) Current Management of the Infant Who Presents with Neonatal Encephalopathy. Current Problems in Pediatric and Adolescent Health Care 41:5, 132-153
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Mario Herrera-Marschitz, Paola Morales, Lisette Leyton, Diego Bustamante, Verena Klawitter, Pablo Espina-Marchant, Camilo Allende, Francisco Lisboa, Gabriel Cunich, Antonella Jara-Cavieres, Tanya Neira, Manuel A. Gutierrez-Hernandez, Victor Gonzalez-Lira, Nicola Simola, Andrea Schmitt, Micaela Morelli, R. Andrew Tasker, Peter J. Gebicke-Haerter. (2011) Perinatal asphyxia: current status and approaches towards neuroprotective strategies, with focus on sentinel proteins. Neurotoxicity Research 19:4, 603-627
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Alexis Topjian, Larissa Hutchins, Mary Ann DiLiberto, Nicholas S. Abend, Rebecca Ichord, Mark Helfaer, Robert A. Berg, Vinay Nadkarni. (2011) Induction and maintenance of therapeutic hypothermia after pediatric cardiac arrest: Efficacy of a surface cooling protocol*. Pediatric Critical Care Medicine 12:3, e127-e135
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John Madar. (2011) Resuscitation of the newborn. Anaesthesia & Intensive Care Medicine 12:4, 135-140
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Michael V Johnston, Ali Fatemi, Mary Ann Wilson, Frances Northington. (2011) Treatment advances in neonatal neuroprotection and neurointensive care. The Lancet Neurology 10:4, 372-382
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Shuying Lin, Philip G. Rhodes, Zhengwei Cai. (2011) Whole body hypothermia broadens the therapeutic window of intranasally administered IGF-1 in a neonatal rat model of cerebral hypoxia–ischemia. Brain Research 1385, 246-256
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Luca Filippi, Giancarlo la Marca, Giacomo Cavallaro, Patrizio Fiorini, Federica Favelli, Sabrina Malvagia, Gianpaolo Donzelli, Renzo Guerrini. (2011) Phenobarbital for neonatal seizures in hypoxic ischemic encephalopathy: A pharmacokinetic study during whole body hypothermia. Epilepsia 52:4, 794-801
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Edward L. Korn, Boris Freidlin. (2011) Inefficacy Interim Monitoring Procedures in Randomized Clinical Trials: The Need to Report. The American Journal of Bioethics 11:3, 2-10
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Xun Liu, Ela Chakkarapani, Nicholas Hoque, Marianne Thoresen. (2011) Environmental cooling of the newborn pig brain during whole-body cooling. Acta Paediatrica 100:1, 29-35
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(2011) Extended Abstracts. Neonatology 100:3, 319-341
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Philippe Bonnin, Pierre-Louis Leger, Nicolas Deroide, Sébastien Fau, Olivier Baud, Marc Pocard, Christiane Charriaut-Marlangue, Sylvain Renolleau. (2011) Impact of intracranial blood-flow redistribution on stroke size during ischemia–reperfusion in 7-day-old rats. Journal of Neuroscience Methods
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Courtney J. Wusthoff, Chris Feudtner. (2011) Physician Opinions Regarding Informed Consent for a “Cutting-Edge” Intervention for Critically Ill Neonates. AJOB Primary Research 2:1, 18-25
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Frank Shann, Andrew C. Argent, Suchitra Ranjit. 2011. Pediatric Intensive Care in Developing Countries. , 164-178.
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Ericka L. Fink, Robert S.B. Clark, Patrick M. Kochanek. 2011. Hypoxic-Ischemic Encephalopathy. , 871-892.
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Shinya Imada, Masahiro Yamamoto, Kayoko Tanaka, Chika Seiwa, Kenji Watanabe, Yoshimasa Kamei, Shiro Kozuma, Yuji Taketani, Hiroaki Asou. (2010) Hypothermia-induced increase of oligodendrocyte precursor cells: Possible involvement of plasmalemmal voltage-dependent anion channel 1. Journal of Neuroscience Research 88:16, 3457-3466
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