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 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 neon...

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Hoofdauteurs: Rutherford, M, Ramenghi, L, Edwards, A, Brocklehurst, P, Halliday, H, Levene, M, Strohm, B, Thoresen, M, Whitelaw, A, Azzopardi, D
Formaat: Journal article
Taal:English
Gepubliceerd in: 2010
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author Rutherford, M
Ramenghi, L
Edwards, A
Brocklehurst, P
Halliday, H
Levene, M
Strohm, B
Thoresen, M
Whitelaw, A
Azzopardi, D
author_facet Rutherford, M
Ramenghi, L
Edwards, A
Brocklehurst, P
Halliday, H
Levene, M
Strohm, B
Thoresen, M
Whitelaw, A
Azzopardi, D
author_sort Rutherford, M
collection OXFORD
description 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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spelling oxford-uuid:7f824a49-ed0e-41f2-b867-679247e42e982022-03-26T21:17:25ZAssessment of brain tissue injury after moderate hypothermia in neonates with hypoxic-ischaemic encephalopathy: a nested substudy of a randomised controlled trial.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:7f824a49-ed0e-41f2-b867-679247e42e98EnglishSymplectic Elements at Oxford2010Rutherford, MRamenghi, LEdwards, ABrocklehurst, PHalliday, HLevene, MStrohm, BThoresen, MWhitelaw, AAzzopardi, DBACKGROUND: 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.
spellingShingle Rutherford, M
Ramenghi, L
Edwards, A
Brocklehurst, P
Halliday, H
Levene, M
Strohm, B
Thoresen, M
Whitelaw, A
Azzopardi, D
Assessment of brain tissue injury after moderate hypothermia in neonates with hypoxic-ischaemic encephalopathy: a nested substudy of a randomised controlled trial.
title Assessment of brain tissue injury after moderate hypothermia in neonates with hypoxic-ischaemic encephalopathy: a nested substudy of a randomised controlled trial.
title_full Assessment of brain tissue injury after moderate hypothermia in neonates with hypoxic-ischaemic encephalopathy: a nested substudy of a randomised controlled trial.
title_fullStr Assessment of brain tissue injury after moderate hypothermia in neonates with hypoxic-ischaemic encephalopathy: a nested substudy of a randomised controlled trial.
title_full_unstemmed Assessment of brain tissue injury after moderate hypothermia in neonates with hypoxic-ischaemic encephalopathy: a nested substudy of a randomised controlled trial.
title_short Assessment of brain tissue injury after moderate hypothermia in neonates with hypoxic-ischaemic encephalopathy: a nested substudy of a randomised controlled trial.
title_sort assessment of brain tissue injury after moderate hypothermia in neonates with hypoxic ischaemic encephalopathy a nested substudy of a randomised controlled trial
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