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 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.


RESULTS
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.


CONCLUSIONS
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.


BACKGROUND
UK Medical Research Council; UK Department of Health.
Rutherford
Mary
M
Perinatal Imaging, MRC Clinical Sciences Centre, Hammersmith Hospital, London, UK.
Ramenghi
Luca A
LA
Edwards
A David
AD
Brocklehurst
Peter
P
Halliday
Henry
H
Levene
Malcolm
M
Strohm
Brenda
B
Thoresen
Marianne
M
Whitelaw
Andrew
A
Azzopardi
Denis
D
D000367:Age Factors; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D004569:Electroencephalography; D005260:Female; D006801:Humans; D007036:Hypothermia, Induced; D020925:Hypoxia-Ischemia, Brain / Q000473:pathology* / Q000503:physiopathology / Q000628:therapy*; D007231:Infant, Newborn; D016015:Logistic Models; D008279:Magnetic Resonance Imaging; D008297:Male; D009468:Neuromuscular Diseases / Q000175:diagnosis / Q000209:etiology / Q000473:pathology; D016017:Odds Ratio; D011379:Prognosis; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D016896:Treatment Outcome