OBJECTIVES

To determine the neurodevelopmental outcome of infants treated with head cooling with systemic hypothermia after hypoxic-ischemic encephalopathy.

STUDY DESIGN

Infants >/=37 weeks' gestation, who had an umbilical artery pH </=7.09 or Apgar score </=6 at 5 minutes, plus clinical encephalopathy. Infants with major congenital abnormalities were excluded.

TRIAL DESIGN

Infants were allocated to either no cooling (rectal temperature = 37.0 +/- 0.2 degrees C, n = 15), or, sequentially, to head cooling accompanied by different levels of systemic hypothermia, including minimal cooling, rectal temperature 36.5 degrees C to 36 degrees C (n = 6), and mild cooling, to either 35.9 degrees C to 35.5 degrees C (n = 6), 35 +/- 0.5 degrees C (n = 6) or 34.5 +/- 0.5 degrees C (n = 7). Head cooling was accomplished by circulating cooled water through a coil of tubing wrapped around the head for up to 72 hours. Survivors were followed up with regular neurologic examination by a neonatologist until 18 months of age, then with blinded developmental testing using the revised Bayley Scales.

RESULTS

A total of 40 term infants were enrolled from 2 to 5 hours after birth. The control and the cooled groups were not significantly different for gestation, birth weight, Apgar score, and initial pH. There were 6 early neonatal deaths (3 normothermic and 3 cooled), and 1 death in infancy associated with severe spastic cerebral palsy in a normothermic infant. Six normothermic, 1 minimally cooled, and 4 mildly cooled infants had early stage 1 encephalopathy; all but 1 had a good outcome. Among infants with early stage 2 or 3 encephalopathy, an adverse outcome was found in 4 of 9 normothermic infants (44%) and 4 of 5 minimally cooled infants (80%), whereas in the combined mildly cooled groups, an adverse outcome was found in 4 of 15 infants (26%, odds ratio 0.46 [0.08, 2.56] vs normothermia).

CONCLUSIONS

The present study supports the safety of hypothermia, with no evidence of late adverse effects in any infant. Among infants with moderate to severe encephalopathy at enrollment, there was a tendency toward better outcome. These results emphasize the relatively wide range of outcomes using purely clinical criteria for enrollment. Therapeutic hypothermia should not be used outside of stringent, multicenter trials.