The authors report on the results of the CoolCap Study, a multi-center project including 25 perinatal centers. Study patients were infants ≥36 weeks gestational age with evidence of perinatal hypoxia-ischemia and an abnormal EEG. Inclusion criteria included an Apgar score ≤5 at 10 minutes after birth, a continued need for resuscitation (endotracheal or mask ventilation) at 10 minutes after birth, or severe acidosis (pH<7.00) within 60 minutes of birth. Eligible infants were assessed for evidence of moderate to severe encephalopathy (according to the criteria of Sarnat and Sarnat)1 or clinical evidence of seizures. An amplitude integrated EEG was performed >1 hour after birth and infants were selected for the study if the background voltage demonstrated moderately to severely abnormal background or seizures. The authors hypothesized that the moderate group would be more likely to benefit from cooling.
Infants randomized to cooling (n=112) were fitted with a cooling cap (Olympic Medical Cool Care System, Olympic Medical, Seattle, WA) around the head and treated within 6 hours of birth for 72 hours. The system contains a pump that circulates water between 8–12°C. The infant was kept under a radiant heater adjusted to maintain rectal temperature 34–35°C. Control infants (n=118) had temperature goals of 36.5–37.5°C and did not have a cooling cap. Care was otherwise consistent with usual standards, with the exception that cooled infants were not fed during the 72-hour study period. Mild hypothermia was well tolerated except for mild hyperglycemia in the treatment group that resolved within 24 hours and scalp edema in 32 treated infants that resolved after cooling.
Infants were assessed at 18 months of age with visual and auditory testing, the Bayley II scales,2 and the Gross Motor Function (GMF) Classification.3 Severe disability was defined as a Bayley index <70, GMF level 3–5 (non-ambulatory, sits with support, or no self mobility), or bilateral cortical visual impairment. Of the 218 infants assessed, 172 had less severe EEG findings at enrollment while 46 had severe EEG changes; infants within these 2 groups had been randomized equally to treatment or control groups.
For the entire study population, cooling was associated with a trend of decreased risk of death or severe disability (OR 0.61; 95% CI, 0.34–1.09). In the moderate severity group, 12% of cooled patients had severe neuromotor disability compared to 28% of control patients (P=.03), while 25% had a Bayley Mental Index <70 compared to 40% of control patients (P=.15). Fewer cooled intermediate EEG patients tended to develop multiple disabilities (14% vs. 28%, P=.1) after adjustment for seizures and age at randomization. The multivariate analysis for cooling restricted to the intermediate EEG group showed a >50% decreased risk of severe disability (OR 0.42; 95% CI, 0.22–0.8). The authors concluded that after anoxic ischemic events, head cooling with moderate systemic...