TOBY

Whole body hypothermia for the treatment of perinatal asphyxial encephalopathy.

Trial started: 2002  Trial ended: 2008 

Summary

Objectives

To determine whether moderate whole-body hypothermia improves outcomes in newborn infants with perinatal asphyxial encephalopathy.

Methods

A randomised controlled trial involving 325 infants born at ?36 weeks' gestation with perinatal asphyxial encephalopathy. Infants were randomised within 6 hours of birth to receive either standard intensive care with whole-body cooling to 33.5°C for 72 hours or standard intensive care alone.

Outcome measures

Primary outcome: Death or severe neurodevelopmental disability at 18 months of age.

Secondary outcomes included neurological outcomes, developmental scores and adverse outcomes.

Results

Of the 325 infants enrolled, 163 were allocated to hypothermia and 162 to standard care alone. In the hypothermia group, 42 infants died and 32 survived with severe neurodevelopmental disability, compared with 44 deaths and 42 survivors with severe disability in the control group. There was no statistically significant difference in the combined primary outcome of death or severe disability (relative risk 0.86, 95% confidence interval 0.68 to 1.07; p = 0.17). However, infants receiving hypothermia were more likely to survive without neurological abnormality (relative risk 1.57, 95% confidence interval 1.16 to 2.12; p = 0.003). Among survivors, hypothermia was associated with a lower risk of cerebral palsy and better mental, psychomotor and gross motor function scores. Adverse events were mostly minor and were not associated with hypothermia.

Conclusions

Moderate hypothermia did not significantly reduce the combined outcome of death or severe disability at 18 months, but was associated with improved neurological outcomes among survivors.

Summary based on: Azzopardi DV, Strohm B, Edwards AD, et al. Moderate hypothermia to treat perinatal asphyxial encephalopathy. New England Journal of Medicine. 2009;361(14):1349–1358. https://doi.org/10.1056/NEJMoa0900854.