Brenda Strohm - Academia.edu (original) (raw)

Papers by Brenda Strohm

Research paper thumbnail of Moderate hypothermia within 6 h of birth plus inhaled xenon versus moderate hypothermia alone after birth asphyxia (TOBY-Xe): a proof-of-concept, open-label, randomised controlled trial

The Lancet Neurology, 2015

Moderate cooling after birth asphyxia is associated with substantial reductions in death and disa... more Moderate cooling after birth asphyxia is associated with substantial reductions in death and disability, but additional therapies might provide further benefit. We assessed whether the addition of xenon gas, a promising novel therapy, after the initiation of hypothermia for birth asphyxia would result in further improvement. Total Body hypothermia plus Xenon (TOBY-Xe) was a proof-of-concept, randomised, open-label, parallel-group trial done at four intensive-care neonatal units in the UK. Eligible infants were 36-43 weeks of gestational age, had signs of moderate to severe encephalopathy and moderately or severely abnormal background activity for at least 30 min or seizures as shown by amplitude-integrated EEG (aEEG), and had one of the following: Apgar score of 5 or less 10 min after birth, continued need for resuscitation 10 min after birth, or acidosis within 1 h of birth. Participants were allocated in a 1:1 ratio by use of a secure web-based computer-generated randomisation sequence within 12 h of birth to cooling to a rectal temperature of 33·5°C for 72 h (standard treatment) or to cooling in combination with 30% inhaled xenon for 24 h started immediately after randomisation. The primary outcomes were reduction in lactate to N-acetyl aspartate ratio in the thalamus and in preserved fractional anisotropy in the posterior limb of the internal capsule, measured with magnetic resonance spectroscopy and MRI, respectively, within 15 days of birth. The investigator assessing these outcomes was masked to allocation. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00934700, and with ISRCTN, as ISRCTN08886155. The study was done from Jan 31, 2012, to Sept 30, 2014. We enrolled 92 infants, 46 of whom were randomly assigned to cooling only and 46 to xenon plus cooling. 37 infants in the cooling only group and 41 in the cooling plus xenon group underwent magnetic resonance assessments and were included in the analysis of the primary outcomes. We noted no significant differences in lactate to N-acetyl aspartate ratio in the thalamus (geometric mean ratio 1·09, 95% CI 0·90 to 1·32) or fractional anisotropy (mean difference -0·01, 95% CI -0·03 to 0·02) in the posterior limb of the internal capsule between the two groups. Nine infants died in the cooling group and 11 in the xenon group. Two adverse events were reported in the xenon group: subcutaneous fat necrosis and transient desaturation during the MRI. No serious adverse events were recorded. Administration of xenon within the delayed timeframe used in this trial is feasible and apparently safe, but is unlikely to enhance the neuroprotective effect of cooling after birth asphyxia. UK Medical Research Council.

Research paper thumbnail of Cooling for neonatal encephalopathy in 2010

Research paper thumbnail of Should neonatal encephalopathy now be treated with cooling

The use of selective and systemic induced mild hypothermia for the treatment of neonatal encephal... more The use of selective and systemic induced mild hypothermia for the treatment of neonatal encephalopathy has been the subject of several randomised controlled trials over recent years. The largest of these, the TOBY Study, has recently completed recruitment. This article discusses the current status of hypothermia and how its use might evolve in the near future.

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

PLoS ONE, 2012

Delay in implementing new treatments into clinical practice results in considerable health and ec... more 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. 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). 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.

Research paper thumbnail of The TOBY Study parents' online message board

Journal of Neonatal Nursing, 2007

The TOBY Study is a randomised controlled trial that recruited term babies with neonatal encephal... more The TOBY Study is a randomised controlled trial that recruited term babies with neonatal encephalopathy from December 2002 for 4 years. Assessment of the baby, obtaining informed consent from parents and allocation of intensive care treatment with cooling or without cooling had to be completed by 6 h of age. Parents who agreed to enter their baby into the TOBY Study had been through an extremely stressful experience, having had an unexpectedly complicated birth that resulted in a very sick baby. In order to facilitate parents of TOBY babies contacting each other, BLISS (The Premature Baby Charity) agreed to host a message board for TOBY parents as part of their established online message board system. This article describes how the need for such a facility was identified, how it became a reality and the impact of the message board on those who have chosen to use it.

Research paper thumbnail of To cool or not to cool

Journal of Neonatal Nursing, 2008

This poster was created to highlight the continuing uncertainty surrounding the use of cooling fo... more This poster was created to highlight the continuing uncertainty surrounding the use of cooling for the treatment of neonatal encephalopathy (NE), pending the results of the TOBY Study. In addition it raises awareness of the UK TOBY Cooling Register; all UK neonatal units currently providing cooling as a treatment for NE are encouraged to submit data to this anonymous Register. For more information about the Register please visit the website at www.npeu.ox.ac.uk/tobyregister. *

Research paper thumbnail of Neonatal research update

Journal of Neonatal Nursing, 2012

Research paper thumbnail of Treatment of asphyxiated newborns with moderate hypothermia in routine clinical practice: how cooling is managed in the UK outside a clinical trial

Archives of Disease in Childhood - Fetal and Neonatal Edition, 2009

on behalf of the Steering Group and TOBY Cooling Register participants c An additional appendix i... more on behalf of the Steering Group and TOBY Cooling Register participants c An additional appendix is published online only at

Research paper thumbnail of Assessment of brain tissue injury after moderate hypothermia in neonates with hypoxic-ischaemic encephalopathy: a nested substudy of a randomised controlled trial

Background Moderate hypothermia in neonates with hypoxic-ischaemic encephalopathy might improve s... more Background Moderate hypothermia in neonates with hypoxic-ischaemic encephalopathy might improve survival and neurological outcomes at up to 18 months of age, although complete neurological assessment at this age is diffi cult. To ascertain more precisely the eff ect of therapeutic hypothermia on neonatal cerebral injury, we assessed cerebral lesions on MRI scans of infants who participated in the Total Body Hypothermia for Neonatal Encephalopathy (TOBY) trial.

Research paper thumbnail of Neurological outcomes at 18 months of age after moderate hypothermia for perinatal hypoxic ischaemic encephalopathy: synthesis and meta-analysis of trial data

BMJ, 2010

of physiology, 4 Henry Halliday, professor of perinatal medicine, 5,6 Edmund Juszczak, head of tr... more of physiology, 4 Henry Halliday, professor of perinatal medicine, 5,6 Edmund Juszczak, head of trials , 3 Malcolm Levene, professor of paediatrics and child health, 7,8 Brenda Strohm, trial coordinator, 3 Marianne Thoresen, professor of neonatal neuroscience, 9 Andrew Whitelaw, professor of neonatal medicine, 9 Denis Azzopardi, clinical reader in neonatal medicine 1,2 ABSTRACT Objective To determine whether moderate hypothermia after hypoxic-ischaemic encephalopathy in neonates improves survival and neurological outcome at 18 months of age. Design A meta-analysis was performed using a fixed effect model. Risk ratios, risk difference, and number needed to treat, plus 95% confidence intervals, were measured. Data sources Studies were identified from the Cochrane central register of controlled trials, the Oxford database of perinatal trials, PubMed, previous reviews, and abstracts. Review methods Reports that compared whole body cooling or selective head cooling with normal care in neonates with hypoxic-ischaemic encephalopathy and that included data on death or disability and on specific neurological outcomes of interest to patients and clinicians were selected. Results We found three trials, encompassing 767 infants, that included information on death and major neurodevelopmental disability after at least 18 months' follow-up. We also identified seven other trials with mortality information but no appropriate neurodevelopmental data. Therapeutic hypothermia significantly reduced the combined rate of death and severe disability in the three trials with 18 month outcomes (risk ratio 0.81, 95% confidence interval 0.71 to 0.93, P=0.002; risk difference −0.11, 95% CI −0.18 to −0.04), with a number needed to treat of nine (95% CI 5 to 25). Hypothermia increased survival with normal neurological function (risk ratio 1.53, 95% CI 1.22 to 1.93, P<0.001; risk difference 0.12, 95% CI 0.06 to 0.18), with a number needed to treat of eight (95% CI 5 to 17), and in survivors reduced the rates of severe disability (P=0.006), cerebral palsy (P=0.004), and mental and the psychomotor developmental index of less than 70 (P=0.01 and P=0.02, respectively). No significant interaction between severity of encephalopathy and treatment effect was detected. Mortality was significantly reduced when we assessed all 10 trials (1320 infants; relative risk 0.78, 95% CI 0.66 to 0.93, P=0.005; risk difference −0.07, 95% CI −0.12 to −0.02), with a number needed to treat of 14 (95% CI 8 to 47). Conclusions In infants with hypoxic-ischaemic encephalopathy, moderate hypothermia is associated with a consistent reduction in death and neurological impairment at 18 months.

Research paper thumbnail of Effects of Hypothermia for Perinatal Asphyxia on Childhood Outcomes

The Journal of Emergency Medicine, 2014

Moderate hypothermia after perinatal asphyxia resulted in improved neurocognitive outcomes in mid... more Moderate hypothermia after perinatal asphyxia resulted in improved neurocognitive outcomes in middle childhood. (Funded by the United Kingdom Medical Research Council and others; TOBY ClinicalTrials.gov number, NCT01092637.)

Research paper thumbnail of Subcutaneous Fat Necrosis After Moderate Therapeutic Hypothermia in Neonates

PEDIATRICS, 2011

Therapeutic moderate hypothermia in newborns with hypoxic-ischemic encephalopathy is rapidly beco... more Therapeutic moderate hypothermia in newborns with hypoxic-ischemic encephalopathy is rapidly becoming standard clinical practice. We report here 12 cases of subcutaneous fat necrosis among 1239 cases registered with a national registry of newborns treated with moderate whole-body hypothermia. All the infants suffered from perinatal asphyxia and hypoxic-ischemic encephalopathy. Moderate-to-severe hypercalcemia was identified in 8 of 10 infants with blood calcium measurements. In all cases the skin lesions appeared after completion of the cooling treatment. Our data suggest that prolonged moderate hypothermia is an actual risk factor for subcutaneous fat necrosis. Because the lesions often develop several days after birth, physicians need to be aware of this condition as a possible complication in infants treated with moderate hypothermia after asphyxia. Blood calcium levels need to be monitored in affected infants.

Research paper thumbnail of Moderate Hypothermia to Treat Perinatal Asphyxial Encephalopathy

New England Journal of Medicine, 2009

Whether hypothermic therapy improves neurodevelopmental outcomes in newborn infants with asphyxia... more Whether hypothermic therapy improves neurodevelopmental outcomes in newborn infants with asphyxial encephalopathy is uncertain.

Research paper thumbnail of Assessment of brain tissue injury after moderate hypothermia in neonates with hypoxic–ischaemic encephalopathy: a nested substudy of a randomised controlled trial

The Lancet Neurology, 2010

Background-Moderate hypothermia in neonates with hypoxic-ischaemic encephalopathy might improve s... more Background-Moderate hypothermia in neonates with hypoxic-ischaemic encephalopathy might improve survival and neurological outcomes at up to 18 months of age, although complete neurological assessment at this age is difficult. To ascertain more precisely the effect of therapeutic hypothermia on neonatal cerebral injury, we assessed cerebral lesions on MRI scans of infants who participated in the Total Body Hypothermia for Neonatal Encephalopathy (TOBY) trial.

Research paper thumbnail of Neurological outcomes at 18 months of age after moderate hypothermia for perinatal hypoxic ischaemic encephalopathy: synthesis and meta-analysis of trial data

BMJ, 2010

of physiology, 4 Henry Halliday, professor of perinatal medicine, 5,6 Edmund Juszczak, head of tr... more of physiology, 4 Henry Halliday, professor of perinatal medicine, 5,6 Edmund Juszczak, head of trials , 3 Malcolm Levene, professor of paediatrics and child health, 7,8 Brenda Strohm, trial coordinator, 3 Marianne Thoresen, professor of neonatal neuroscience, 9 Andrew Whitelaw, professor of neonatal medicine, 9 Denis Azzopardi, clinical reader in neonatal medicine 1,2 ABSTRACT Objective To determine whether moderate hypothermia after hypoxic-ischaemic encephalopathy in neonates improves survival and neurological outcome at 18 months of age. Design A meta-analysis was performed using a fixed effect model. Risk ratios, risk difference, and number needed to treat, plus 95% confidence intervals, were measured. Data sources Studies were identified from the Cochrane central register of controlled trials, the Oxford database of perinatal trials, PubMed, previous reviews, and abstracts. Review methods Reports that compared whole body cooling or selective head cooling with normal care in neonates with hypoxic-ischaemic encephalopathy and that included data on death or disability and on specific neurological outcomes of interest to patients and clinicians were selected. Results We found three trials, encompassing 767 infants, that included information on death and major neurodevelopmental disability after at least 18 months' follow-up. We also identified seven other trials with mortality information but no appropriate neurodevelopmental data. Therapeutic hypothermia significantly reduced the combined rate of death and severe disability in the three trials with 18 month outcomes (risk ratio 0.81, 95% confidence interval 0.71 to 0.93, P=0.002; risk difference −0.11, 95% CI −0.18 to −0.04), with a number needed to treat of nine (95% CI 5 to 25). Hypothermia increased survival with normal neurological function (risk ratio 1.53, 95% CI 1.22 to 1.93, P<0.001; risk difference 0.12, 95% CI 0.06 to 0.18), with a number needed to treat of eight (95% CI 5 to 17), and in survivors reduced the rates of severe disability (P=0.006), cerebral palsy (P=0.004), and mental and the psychomotor developmental index of less than 70 (P=0.01 and P=0.02, respectively). No significant interaction between severity of encephalopathy and treatment effect was detected. Mortality was significantly reduced when we assessed all 10 trials (1320 infants; relative risk 0.78, 95% CI 0.66 to 0.93, P=0.005; risk difference −0.07, 95% CI −0.12 to −0.02), with a number needed to treat of 14 (95% CI 8 to 47). Conclusions In infants with hypoxic-ischaemic encephalopathy, moderate hypothermia is associated with a consistent reduction in death and neurological impairment at 18 months.

Research paper thumbnail of Treatment of asphyxiated newborns with moderate hypothermia in routine clinical practice: how cooling is managed in the UK outside a clinical trial

Archives of Disease in Childhood - Fetal and Neonatal Edition, 2009

on behalf of the Steering Group and TOBY Cooling Register participants c An additional appendix i... more on behalf of the Steering Group and TOBY Cooling Register participants c An additional appendix is published online only at

Research paper thumbnail of Moderate hypothermia within 6 h of birth plus inhaled xenon versus moderate hypothermia alone after birth asphyxia (TOBY-Xe): a proof-of-concept, open-label, randomised controlled trial

The Lancet Neurology, 2015

Moderate cooling after birth asphyxia is associated with substantial reductions in death and disa... more Moderate cooling after birth asphyxia is associated with substantial reductions in death and disability, but additional therapies might provide further benefit. We assessed whether the addition of xenon gas, a promising novel therapy, after the initiation of hypothermia for birth asphyxia would result in further improvement. Total Body hypothermia plus Xenon (TOBY-Xe) was a proof-of-concept, randomised, open-label, parallel-group trial done at four intensive-care neonatal units in the UK. Eligible infants were 36-43 weeks of gestational age, had signs of moderate to severe encephalopathy and moderately or severely abnormal background activity for at least 30 min or seizures as shown by amplitude-integrated EEG (aEEG), and had one of the following: Apgar score of 5 or less 10 min after birth, continued need for resuscitation 10 min after birth, or acidosis within 1 h of birth. Participants were allocated in a 1:1 ratio by use of a secure web-based computer-generated randomisation sequence within 12 h of birth to cooling to a rectal temperature of 33·5°C for 72 h (standard treatment) or to cooling in combination with 30% inhaled xenon for 24 h started immediately after randomisation. The primary outcomes were reduction in lactate to N-acetyl aspartate ratio in the thalamus and in preserved fractional anisotropy in the posterior limb of the internal capsule, measured with magnetic resonance spectroscopy and MRI, respectively, within 15 days of birth. The investigator assessing these outcomes was masked to allocation. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00934700, and with ISRCTN, as ISRCTN08886155. The study was done from Jan 31, 2012, to Sept 30, 2014. We enrolled 92 infants, 46 of whom were randomly assigned to cooling only and 46 to xenon plus cooling. 37 infants in the cooling only group and 41 in the cooling plus xenon group underwent magnetic resonance assessments and were included in the analysis of the primary outcomes. We noted no significant differences in lactate to N-acetyl aspartate ratio in the thalamus (geometric mean ratio 1·09, 95% CI 0·90 to 1·32) or fractional anisotropy (mean difference -0·01, 95% CI -0·03 to 0·02) in the posterior limb of the internal capsule between the two groups. Nine infants died in the cooling group and 11 in the xenon group. Two adverse events were reported in the xenon group: subcutaneous fat necrosis and transient desaturation during the MRI. No serious adverse events were recorded. Administration of xenon within the delayed timeframe used in this trial is feasible and apparently safe, but is unlikely to enhance the neuroprotective effect of cooling after birth asphyxia. UK Medical Research Council.

Research paper thumbnail of Cooling for neonatal encephalopathy in 2010

Research paper thumbnail of Should neonatal encephalopathy now be treated with cooling

The use of selective and systemic induced mild hypothermia for the treatment of neonatal encephal... more The use of selective and systemic induced mild hypothermia for the treatment of neonatal encephalopathy has been the subject of several randomised controlled trials over recent years. The largest of these, the TOBY Study, has recently completed recruitment. This article discusses the current status of hypothermia and how its use might evolve in the near future.

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

PLoS ONE, 2012

Delay in implementing new treatments into clinical practice results in considerable health and ec... more 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. 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&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001) and severely abnormal amplitude integrated EEG (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001). 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.

Research paper thumbnail of The TOBY Study parents' online message board

Journal of Neonatal Nursing, 2007

The TOBY Study is a randomised controlled trial that recruited term babies with neonatal encephal... more The TOBY Study is a randomised controlled trial that recruited term babies with neonatal encephalopathy from December 2002 for 4 years. Assessment of the baby, obtaining informed consent from parents and allocation of intensive care treatment with cooling or without cooling had to be completed by 6 h of age. Parents who agreed to enter their baby into the TOBY Study had been through an extremely stressful experience, having had an unexpectedly complicated birth that resulted in a very sick baby. In order to facilitate parents of TOBY babies contacting each other, BLISS (The Premature Baby Charity) agreed to host a message board for TOBY parents as part of their established online message board system. This article describes how the need for such a facility was identified, how it became a reality and the impact of the message board on those who have chosen to use it.

Research paper thumbnail of To cool or not to cool

Journal of Neonatal Nursing, 2008

This poster was created to highlight the continuing uncertainty surrounding the use of cooling fo... more This poster was created to highlight the continuing uncertainty surrounding the use of cooling for the treatment of neonatal encephalopathy (NE), pending the results of the TOBY Study. In addition it raises awareness of the UK TOBY Cooling Register; all UK neonatal units currently providing cooling as a treatment for NE are encouraged to submit data to this anonymous Register. For more information about the Register please visit the website at www.npeu.ox.ac.uk/tobyregister. *

Research paper thumbnail of Neonatal research update

Journal of Neonatal Nursing, 2012

Research paper thumbnail of Treatment of asphyxiated newborns with moderate hypothermia in routine clinical practice: how cooling is managed in the UK outside a clinical trial

Archives of Disease in Childhood - Fetal and Neonatal Edition, 2009

on behalf of the Steering Group and TOBY Cooling Register participants c An additional appendix i... more on behalf of the Steering Group and TOBY Cooling Register participants c An additional appendix is published online only at

Research paper thumbnail of Assessment of brain tissue injury after moderate hypothermia in neonates with hypoxic-ischaemic encephalopathy: a nested substudy of a randomised controlled trial

Background Moderate hypothermia in neonates with hypoxic-ischaemic encephalopathy might improve s... more Background Moderate hypothermia in neonates with hypoxic-ischaemic encephalopathy might improve survival and neurological outcomes at up to 18 months of age, although complete neurological assessment at this age is diffi cult. To ascertain more precisely the eff ect of therapeutic hypothermia on neonatal cerebral injury, we assessed cerebral lesions on MRI scans of infants who participated in the Total Body Hypothermia for Neonatal Encephalopathy (TOBY) trial.

Research paper thumbnail of Neurological outcomes at 18 months of age after moderate hypothermia for perinatal hypoxic ischaemic encephalopathy: synthesis and meta-analysis of trial data

BMJ, 2010

of physiology, 4 Henry Halliday, professor of perinatal medicine, 5,6 Edmund Juszczak, head of tr... more of physiology, 4 Henry Halliday, professor of perinatal medicine, 5,6 Edmund Juszczak, head of trials , 3 Malcolm Levene, professor of paediatrics and child health, 7,8 Brenda Strohm, trial coordinator, 3 Marianne Thoresen, professor of neonatal neuroscience, 9 Andrew Whitelaw, professor of neonatal medicine, 9 Denis Azzopardi, clinical reader in neonatal medicine 1,2 ABSTRACT Objective To determine whether moderate hypothermia after hypoxic-ischaemic encephalopathy in neonates improves survival and neurological outcome at 18 months of age. Design A meta-analysis was performed using a fixed effect model. Risk ratios, risk difference, and number needed to treat, plus 95% confidence intervals, were measured. Data sources Studies were identified from the Cochrane central register of controlled trials, the Oxford database of perinatal trials, PubMed, previous reviews, and abstracts. Review methods Reports that compared whole body cooling or selective head cooling with normal care in neonates with hypoxic-ischaemic encephalopathy and that included data on death or disability and on specific neurological outcomes of interest to patients and clinicians were selected. Results We found three trials, encompassing 767 infants, that included information on death and major neurodevelopmental disability after at least 18 months' follow-up. We also identified seven other trials with mortality information but no appropriate neurodevelopmental data. Therapeutic hypothermia significantly reduced the combined rate of death and severe disability in the three trials with 18 month outcomes (risk ratio 0.81, 95% confidence interval 0.71 to 0.93, P=0.002; risk difference −0.11, 95% CI −0.18 to −0.04), with a number needed to treat of nine (95% CI 5 to 25). Hypothermia increased survival with normal neurological function (risk ratio 1.53, 95% CI 1.22 to 1.93, P<0.001; risk difference 0.12, 95% CI 0.06 to 0.18), with a number needed to treat of eight (95% CI 5 to 17), and in survivors reduced the rates of severe disability (P=0.006), cerebral palsy (P=0.004), and mental and the psychomotor developmental index of less than 70 (P=0.01 and P=0.02, respectively). No significant interaction between severity of encephalopathy and treatment effect was detected. Mortality was significantly reduced when we assessed all 10 trials (1320 infants; relative risk 0.78, 95% CI 0.66 to 0.93, P=0.005; risk difference −0.07, 95% CI −0.12 to −0.02), with a number needed to treat of 14 (95% CI 8 to 47). Conclusions In infants with hypoxic-ischaemic encephalopathy, moderate hypothermia is associated with a consistent reduction in death and neurological impairment at 18 months.

Research paper thumbnail of Effects of Hypothermia for Perinatal Asphyxia on Childhood Outcomes

The Journal of Emergency Medicine, 2014

Moderate hypothermia after perinatal asphyxia resulted in improved neurocognitive outcomes in mid... more Moderate hypothermia after perinatal asphyxia resulted in improved neurocognitive outcomes in middle childhood. (Funded by the United Kingdom Medical Research Council and others; TOBY ClinicalTrials.gov number, NCT01092637.)

Research paper thumbnail of Subcutaneous Fat Necrosis After Moderate Therapeutic Hypothermia in Neonates

PEDIATRICS, 2011

Therapeutic moderate hypothermia in newborns with hypoxic-ischemic encephalopathy is rapidly beco... more Therapeutic moderate hypothermia in newborns with hypoxic-ischemic encephalopathy is rapidly becoming standard clinical practice. We report here 12 cases of subcutaneous fat necrosis among 1239 cases registered with a national registry of newborns treated with moderate whole-body hypothermia. All the infants suffered from perinatal asphyxia and hypoxic-ischemic encephalopathy. Moderate-to-severe hypercalcemia was identified in 8 of 10 infants with blood calcium measurements. In all cases the skin lesions appeared after completion of the cooling treatment. Our data suggest that prolonged moderate hypothermia is an actual risk factor for subcutaneous fat necrosis. Because the lesions often develop several days after birth, physicians need to be aware of this condition as a possible complication in infants treated with moderate hypothermia after asphyxia. Blood calcium levels need to be monitored in affected infants.

Research paper thumbnail of Moderate Hypothermia to Treat Perinatal Asphyxial Encephalopathy

New England Journal of Medicine, 2009

Whether hypothermic therapy improves neurodevelopmental outcomes in newborn infants with asphyxia... more Whether hypothermic therapy improves neurodevelopmental outcomes in newborn infants with asphyxial encephalopathy is uncertain.

Research paper thumbnail of Assessment of brain tissue injury after moderate hypothermia in neonates with hypoxic–ischaemic encephalopathy: a nested substudy of a randomised controlled trial

The Lancet Neurology, 2010

Background-Moderate hypothermia in neonates with hypoxic-ischaemic encephalopathy might improve s... more Background-Moderate hypothermia in neonates with hypoxic-ischaemic encephalopathy might improve survival and neurological outcomes at up to 18 months of age, although complete neurological assessment at this age is difficult. To ascertain more precisely the effect of therapeutic hypothermia on neonatal cerebral injury, we assessed cerebral lesions on MRI scans of infants who participated in the Total Body Hypothermia for Neonatal Encephalopathy (TOBY) trial.

Research paper thumbnail of Neurological outcomes at 18 months of age after moderate hypothermia for perinatal hypoxic ischaemic encephalopathy: synthesis and meta-analysis of trial data

BMJ, 2010

of physiology, 4 Henry Halliday, professor of perinatal medicine, 5,6 Edmund Juszczak, head of tr... more of physiology, 4 Henry Halliday, professor of perinatal medicine, 5,6 Edmund Juszczak, head of trials , 3 Malcolm Levene, professor of paediatrics and child health, 7,8 Brenda Strohm, trial coordinator, 3 Marianne Thoresen, professor of neonatal neuroscience, 9 Andrew Whitelaw, professor of neonatal medicine, 9 Denis Azzopardi, clinical reader in neonatal medicine 1,2 ABSTRACT Objective To determine whether moderate hypothermia after hypoxic-ischaemic encephalopathy in neonates improves survival and neurological outcome at 18 months of age. Design A meta-analysis was performed using a fixed effect model. Risk ratios, risk difference, and number needed to treat, plus 95% confidence intervals, were measured. Data sources Studies were identified from the Cochrane central register of controlled trials, the Oxford database of perinatal trials, PubMed, previous reviews, and abstracts. Review methods Reports that compared whole body cooling or selective head cooling with normal care in neonates with hypoxic-ischaemic encephalopathy and that included data on death or disability and on specific neurological outcomes of interest to patients and clinicians were selected. Results We found three trials, encompassing 767 infants, that included information on death and major neurodevelopmental disability after at least 18 months' follow-up. We also identified seven other trials with mortality information but no appropriate neurodevelopmental data. Therapeutic hypothermia significantly reduced the combined rate of death and severe disability in the three trials with 18 month outcomes (risk ratio 0.81, 95% confidence interval 0.71 to 0.93, P=0.002; risk difference −0.11, 95% CI −0.18 to −0.04), with a number needed to treat of nine (95% CI 5 to 25). Hypothermia increased survival with normal neurological function (risk ratio 1.53, 95% CI 1.22 to 1.93, P<0.001; risk difference 0.12, 95% CI 0.06 to 0.18), with a number needed to treat of eight (95% CI 5 to 17), and in survivors reduced the rates of severe disability (P=0.006), cerebral palsy (P=0.004), and mental and the psychomotor developmental index of less than 70 (P=0.01 and P=0.02, respectively). No significant interaction between severity of encephalopathy and treatment effect was detected. Mortality was significantly reduced when we assessed all 10 trials (1320 infants; relative risk 0.78, 95% CI 0.66 to 0.93, P=0.005; risk difference −0.07, 95% CI −0.12 to −0.02), with a number needed to treat of 14 (95% CI 8 to 47). Conclusions In infants with hypoxic-ischaemic encephalopathy, moderate hypothermia is associated with a consistent reduction in death and neurological impairment at 18 months.

Research paper thumbnail of Treatment of asphyxiated newborns with moderate hypothermia in routine clinical practice: how cooling is managed in the UK outside a clinical trial

Archives of Disease in Childhood - Fetal and Neonatal Edition, 2009

on behalf of the Steering Group and TOBY Cooling Register participants c An additional appendix i... more on behalf of the Steering Group and TOBY Cooling Register participants c An additional appendix is published online only at