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

Mary Rutherford, Luca A. Ramenghi, A. David Edwards, Peter Brocklehurst, Henry Halliday, Malcolm Levene, Brenda Strohm, Marianne Thoresen, Andrew Whitelaw, Denis Azzopardi

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Abstract

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. Methods: In the TOBY trial hypoxic-ischaemic encephalopathy was graded clinically according to the changes seen on amplitude integrated EEG, and infants were randomly assigned to intensive care with or without cooling by central telephone randomisation. The relation between allocation to hypothermia or normothermia and cerebral lesions was assessed by logistic regression with perinatal factors as covariates, and adjusted odds ratios (ORs) were calculated. The TOBY trial is registered, number ISRCTN 89547571. Findings: 325 infants were recruited in the TOBY trial between 2002 and 2006. Images were available for analysis from 131 infants. Therapeutic hypothermia was associated with a reduction in lesions in the basal ganglia or thalamus (OR 0·36, 95% CI 0·15-0·84; p=0·02), white matter (0·30, 0·12-0·77; p=0·01), and abnormal posterior limb of the internal capsule (0·38, 0·17-0·85; p=0·02). Compared with non-cooled infants, cooled infants had fewer scans that were predictive of later neuromotor abnormalities (0·41, 0·18-0·91; p=0·03) and were more likely to have normal scans (2·81, 1·13-6·93; p=0·03). The accuracy of prediction by MRI of death or disability to 18 months of age was 0·84 (0·74-0·94) in the cooled group and 0·81 (0·71-0·91) in the non-cooled group. Interpretation: Therapeutic hypothermia decreases brain tissue injury in infants with hypoxic-ischaemic encephalopathy. The predictive value of MRI for subsequent neurological impairment is not affected by therapeutic hypothermia. Funding: UK Medical Research Council; UK Department of Health.

Original languageEnglish
Pages (from-to)39-45
Number of pages7
JournalThe Lancet Neurology
Volume9
Issue number1
DOIs
Publication statusPublished - Jan 2010

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Brain Hypoxia-Ischemia
Hypothermia
Brain Injuries
Randomized Controlled Trials
Induced Hypothermia
Newborn Infant
Odds Ratio
Internal Capsule
Brain Diseases
Critical Care
Random Allocation
Basal Ganglia
Thalamus
Telephone
Biomedical Research
Electroencephalography
Extremities
Logistic Models
Magnetic Resonance Imaging
Health

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Assessment of brain tissue injury after moderate hypothermia in neonates with hypoxic-ischaemic encephalopathy : a nested substudy of a randomised controlled trial. / Rutherford, Mary; Ramenghi, Luca A.; Edwards, A. David; Brocklehurst, Peter; Halliday, Henry; Levene, Malcolm; Strohm, Brenda; Thoresen, Marianne; Whitelaw, Andrew; Azzopardi, Denis.

In: The Lancet Neurology, Vol. 9, No. 1, 01.2010, p. 39-45.

Research output: Contribution to journalArticle

Rutherford, Mary ; Ramenghi, Luca A. ; Edwards, A. David ; Brocklehurst, Peter ; Halliday, Henry ; Levene, Malcolm ; Strohm, Brenda ; Thoresen, Marianne ; Whitelaw, Andrew ; Azzopardi, Denis. / Assessment of brain tissue injury after moderate hypothermia in neonates with hypoxic-ischaemic encephalopathy : a nested substudy of a randomised controlled trial. In: The Lancet Neurology. 2010 ; Vol. 9, No. 1. pp. 39-45.
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AU - Brocklehurst, Peter

AU - Halliday, Henry

AU - Levene, Malcolm

AU - Strohm, Brenda

AU - Thoresen, Marianne

AU - Whitelaw, Andrew

AU - Azzopardi, Denis

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N2 - 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. Methods: In the TOBY trial hypoxic-ischaemic encephalopathy was graded clinically according to the changes seen on amplitude integrated EEG, and infants were randomly assigned to intensive care with or without cooling by central telephone randomisation. The relation between allocation to hypothermia or normothermia and cerebral lesions was assessed by logistic regression with perinatal factors as covariates, and adjusted odds ratios (ORs) were calculated. The TOBY trial is registered, number ISRCTN 89547571. Findings: 325 infants were recruited in the TOBY trial between 2002 and 2006. Images were available for analysis from 131 infants. Therapeutic hypothermia was associated with a reduction in lesions in the basal ganglia or thalamus (OR 0·36, 95% CI 0·15-0·84; p=0·02), white matter (0·30, 0·12-0·77; p=0·01), and abnormal posterior limb of the internal capsule (0·38, 0·17-0·85; p=0·02). Compared with non-cooled infants, cooled infants had fewer scans that were predictive of later neuromotor abnormalities (0·41, 0·18-0·91; p=0·03) and were more likely to have normal scans (2·81, 1·13-6·93; p=0·03). The accuracy of prediction by MRI of death or disability to 18 months of age was 0·84 (0·74-0·94) in the cooled group and 0·81 (0·71-0·91) in the non-cooled group. Interpretation: Therapeutic hypothermia decreases brain tissue injury in infants with hypoxic-ischaemic encephalopathy. The predictive value of MRI for subsequent neurological impairment is not affected by therapeutic hypothermia. Funding: UK Medical Research Council; UK Department of Health.

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