Less Brain Injury For Infants Starved Of Oxygen At Birth With Therapeutic Cooling And Accurate MRI Prognosis (TOBY Trial)

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Main Category: Pediatrics / Children's Health
Also Included In: Neurology / Neuroscience
Article Date: 06 Nov 2009 - 0:00 PST

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An article published Online First and in the January edition of The Lancet Neurology reports that MRI scans on infants who's brains were oxygen deprived can predict with 80 percent accuracy the likelihood of death or disability by eighteen months. Children whose brains are starved of oxygen at birth suffer less brain injury if they undergo therapeutic cooling. The article is the work of Dr Denis Azzopardi, MRC Clinical Sciences Centre, Imperial College London, UK, and colleagues.

Hypoxic-ischaemic encephalopathy is a condition that can be developed by babies who are starved of oxygen at birth. This is an important cause of mortality and morbidity in newborns. It accounts for about 20 percent of occurrences of cerebral palsy in childhood. The Total Body Hypothermia for Neonatal Encephalopathy (TOBY) trial has already been published. In this trial, infants who were allocated to prolonged moderate hypothermia showed no significant difference in the combined rate of death or disability at eighteen months. However, they had a reduced rate of cerebral palsy and improved mental and psychomotor outcomes compared with those allocated to standard care.

In this new study, the hypothesis is that whole-body cooling would be associated with a reduction in cerebral lesions seen on MRI that are characteristic of hypoxic-ischaemic encephalopathy, including those predicting neurodevelopmental impairments. The authors also proposed that cooling would not alter the accuracy of neonatal MRI for predicting neurological outcome at eighteen months of age. To investigate this hypothesis, they analysed the MRI scans for 131 of the 325 infants enrolled in the TOBY trial.

Results indicated that therapeutic hypothermia was linked to a 30 to 40 percent reduction in lesions in various areas of the brain associated with neurological development. Compared with non-cooled infants, cooled infants had fewer scans that were predictive of later neuromotor abnormalities. Also they were almost three times more likely to have normal scans. The accuracy of prediction by MRI of death or disability to eighteen months of age was similar in both groups. It was 84 percent in the cooled group versus 81 percent in the non-cooled group.

The authors explain: "The accuracy of MRI done during the neonatal period for the prediction of neurological outcomes up to 18 months of age was unaltered by therapeutic hypothermia. In this large cohort of infants who had an MRI after hypoxic-ischaemic encephalopathy, we found no unusual patterns of lesions and no increase in haemorrhagic or thrombotic lesions associated with therapeutic hypothermia."

They write in conclusion: "Our finding that MRI at a median of 8 days accurately predicted outcome at 18 months of age in cooled and non-cooled infants is likely to be generally applicable. These data show that MRI in the neonatal period is qualified as a biomarker of disease and treatment response and might be of use in other neuroprotective studies." In an associated comment, Dr Jeff Neil, Washington University School of Medicine, St. Louis, MO, USA, remarks: "[This study] provides valuable information for clinicians and establishes conventional MRI as a useful biomarker and potential surrogate endpoint for future cooling studies."

He adds: "These findings emphasise the important role of MRI in neuroprotection studies. Appreciation of differential regional neuroprotective effects is crucial for advancing understanding of underlying mechanisms."

"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
DOI:10.1016/S1474-4422(09)70295-9
The Lancet Neurology

Written by Stephanie Brunner (B.A.)
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