Children whose brains are starved of oxygen at birth suffer less brain injury if they undergo therapeutic cooling. An Article published Online First and in the January edition of The Lancet Neurology shows MRI scans on these infants predict with 80% accuracy the likelihood of death or disability by 18 months. The Article is written by Dr Dr Denis Azzopardi, MRC Clinical Sciences Centre, Imperial College London, UK, and colleagues.
Babies who are starved of oxygen at birth can develop a condition called hypoxic–ischaemic encephalopathy.This is an important cause of mortality and morbidity in newborns that accounts for about 20% of occurrences of cerebral palsy in childhood. In the already published Total Body Hypothermia for Neonatal Encephalopathy (TOBY) trial, infants who were allocated to prolonged moderate hypothermia showed no significant difference in the combined rate of death or disability at 18 months but 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 authors hypothesised 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. They also proposed that cooling would not alter the accuracy of neonatal MRI for predicting neurological outcome at 18 months of age. To test this hypothesis, they reviewed the MRI scans for 131 of the 325 infants enrolled in the TOBY trial.
The team found that therapeutic hypothermia was associated with a 30-40% 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, and were nearly three times more likely to have normal scans. The accuracy of prediction by MRI of death or disability to 18 months of age was similar in both groups (84% cooled versus 81% non-cooled).
The authors say: "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 conclude: "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 accompanying Reflection and Reaction comment, Dr Jeff Neil, Washington University School of Medicine, St. Louis, MO, USA, says: "[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."
For Dr Denis Azzopardi, MRC Clinical Sciences Centre Imperial College London, UK, please contact Grace Money, MRC Press Office. T) +44 (0) 207 670 5139 E) grace.money@headoffice.mrc.ac.uk / d.azzopardi@imperial.ac.uk
Dr Jeff Neil, Washington University School of Medicine, St. Louis, MO, USA. T) +1 314 747-1364 E) neil@wustl.edu
For full Article and Reflection and Reaction, see: http://press.thelancet.com/tlnbraincool.pdf
Journal
The Lancet Neurology