Implementation and conduct of therapeutic hypothermia for perinatal asphyxial encephalopathy in the UK--analysis of national data

Abstract

Background: Delay in implementing new treatments into clinical practice results in considerable health and economic opportunity costs. Data from the UK TOBY Cooling Register provides the opportunity to examine how one new effective therapy for newborn infants suspected of suffering asphyxial encephalopathy--therapeutic hypothermia- was implemented in the UK.

Methodology/principal findings: We analysed returned data forms from inception of the Register in December 2006 to the end of July 2011. Data forms were received for 1384 (67%) of the 2069 infants registered. The monthly rate of notifications increased from median {IQR} 18 {15-31} to 33 {30-39} after the announcement of the results of the recent TOBY trial, and to 50 {36-55} after their publication. This rate further increased to 70 {64-83} following official endorsement of the therapy, and is now close to the expected numbers of eligible infants. Cooling was started at 3.3 {1.5-5.5} hours after birth and the time taken to achieve the target 33-34 °C rectal temperature was 1 {0-3} hours. The rectal temperature was in the target range in 83% of measurements. From 2006 to 2011 there was evidence of extension of treatment to slightly less severely affected infants. 278 of 1362 (20%) infants died at 2.9 {1.4-4.1} days of age. The rates of death fell slightly over the period of the Register and, at two years of age cerebral palsy was diagnosed in 22% of infants; half of these were spastic bilateral. Factors independently associated with adverse outcome were clinical seizures prior to cooling (p<0.001) and severely abnormal amplitude integrated EEG (p<0.001).

Conclusions/significance: Therapeutic hypothermia was implemented appropriately within the UK, with significant benefit to patients and the health economy. This may be due in part to participation by neonatal units in clinical trials, the establishment of the national Register, and its endorsement by advisory bodies.

Figure 1. UK TOBY Cooling Register: number of registrations and cooling centres by month.

The horizontal lines indicate the range of expected eligible cases in the UK.

Figure 2. Number of hospitals registering first case in 6 month periods from inception of Register.

Shaded bars indicate hospitals that participated in the TOBY trial and clear bars hospitals that did not participate in the TOBY trial.

Figure 3. Distribution of cooling centres in the UK.

Three centres from Eire contributed data from 35 cases and these are included in this report.

Figure 4. Frequencies of age at start of cooling in hours after birth.

Figure 5. Mean hourly rectal temperature from the start of cooling to 96 hours of age.

Figure 6. Clinical characteristics by year of registration.