Background: A hypoxic-ischaemic insult occurring around the time of birth may result in an encephalopathic state characterised by the need for resuscitation at birth, neurological depression, seizures and electroencephalographic abnormalities. There is an increasing risk of death or neurodevelopmental abnormalities with more severe encephalopathy. Current management consists of maintaining physiological parameters within the normal range and treating seizures with anticonvulsants. Studies in adult and newborn animals have shown that a reduction of body temperature of 3-4 degrees C after cerebral insults is associated with improved histological and behavioural outcome. Pilot studies in infants with encephalopathy of head cooling combined with mild whole body hypothermia and of moderate whole body cooling to 33.5 degrees C have been reported. No complications were noted but the group sizes were too small to evaluate benefit.
Methods/design: TOBY is a multi-centre, prospective, randomised study of term infants after perinatal asphyxia comparing those allocated to "intensive care plus total body cooling for 72 hours" with those allocated to "intensive care without cooling".Full-term infants will be randomised within 6 hours of birth to either a control group with the rectal temperature kept at 37 +/- 0.2 degrees C or to whole body cooling, with rectal temperature kept at 33-34 degrees C for 72 hours. Term infants showing signs of moderate or severe encephalopathy +/- seizures have their eligibility confirmed by cerebral function monitoring. Outcomes will be assessed at 18 months of age using neurological and neurodevelopmental testing methods.
Sample size: At least 236 infants would be needed to demonstrate a 30% reduction in the relative risk of mortality or serious disability at 18 months. Recruitment was ahead of target by seven months and approvals were obtained allowing recruitment to continue to the end of the planned recruitment phase. 325 infants were recruited.
Primary outcome: Combined rate of mortality and severe neurodevelopmental impairment in survivors at 18 months of age. Neurodevelopmental impairment will be defined as any of:* Bayley mental developmental scale score less than 70* Gross Motor Function Classification System Levels III - V* Bilateral cortical visual impairments
Trial registration: Current Controlled Trials ISRCTN89547571.