Background: There is now convincing evidence that in industrialized countries therapeutic hypothermia for
perinatal asphyxial encephalopathy increases survival with normal neurological function. However, the greatest
burden of perinatal asphyxia falls in low and mid-resource settings where it is unclear whether therapeutic
hypothermia is safe and effective.
Aims: Under the UCL Uganda Women’s Health Initiative, a pilot randomized controlled trial in infants with
perinatal asphyxia was set up in the special care baby unit in Mulago Hospital, a large public hospital with ~20,000
births in Kampala, Uganda to determine:
(i) The feasibility of achieving consent, neurological assessment, randomization and whole body cooling to a
core temperature 33-34°C using water bottles
(ii) The temperature profile of encephalopathic infants with standard care
(iii) The pattern, severity and evolution of brain tissue injury as seen on cranial ultrasound and relation with
outcome
(iv) The feasibility of neurodevelopmental follow-up at 18-22 months of age
Methods/Design: Ethical approval was obtained from Makerere University and Mulago Hospital. All infants were
in-born. Parental consent for entry into the trial was obtained. Thirty-six infants were randomized either to standard
care plus cooling (target rectal temperature of 33-34°C for 72 hrs, started within 3 h of birth) or standard care
alone. All other aspects of management were the same. Cooling was performed using water bottles filled with
tepid tap water (25°C). Rectal, axillary, ambient and surface water bottle temperatures were monitored continuously
for the first 80 h. Encephalopathy scoring was performed on days 1-4, a structured, scorable neurological
examination and head circumference were performed on days 7 and 17. Cranial ultrasound was performed on
days 1, 3 and 7 and scored. Griffiths developmental quotient, head circumference, neurological examination and
assessment of gross motor function were obtained at 18-22 months.
Discussion: We will highlight differences in neonatal care and infrastructure that need to be taken into account when
considering a large safety and efficacy RCT of therapeutic hypothermia in low and mid resource settings in the future.