Head cooling improves outcomes in neonatal encephalopathy [Classics Series]

1. Among term infants with neonatal encephalopathy associated with mild EEG changes, those randomized to head cooling had a reduced incidence of death and severe neurodevelopmental disability compared to infants randomized to conventional care.

Original Date of Publication: January 2005

Study Rundown: Hypoxic-ischemic encephalopathy (HIE) is a highly morbid cause of acute neurological injury at birth and occurs in 1-2 babies per 1000 term livebirths. HIE occurs as a result of total brain anoxia, or the deprivation of oxygen affecting the entire brain, and has been implicated in over 20% of neonatal deaths. In severe HIE, neonates demonstrate marked electroencephalography (EEG) changes, are stuporous or flaccid and may demonstrate generalized hypotonia, absent neonatal reflexes, fixed or dilated pupils and cardiorespiratory failure. It is a deeply upsetting diagnosis for both parents and healthcare providers due to the alarming presenting symptoms and lack of clinical interventions known to improve outcomes. Prior studies demonstrating improved neurological recovery in adult cardiac arrest patients treated with moderate hypothermia stimulated neonatologists to apply to the same principle to neonates with HIE. Numerous small research studies demonstrated improved electrophysiological and functional neurologic outcomes following reduction in brain temperature of 2-5°C but treatment protocols varied widely. In the present work, researchers investigated whether 72 hours of selective head cooling started within 6 hours of birth improved neurodevelopmental outcome at 18 months in infants with moderate or severe HIE.

This landmark study demonstrated that selective head cooling started within 6 hours was associated with significantly improved outcomes in infants with mild EEG changes. Infants with more severe EEG changes were less likely to benefit from head cooling. Strengths included the multi-center randomized trial study design and enrollment of an ethnically and geographically diverse population. Limitations included residual confounding by baseline differences whereby more infants in the cooled group showed severely abnormal APGAR scores and EEGs. The vast majority of subjects initiated cooling 4 hours after birth such that the relatively late onset of treatment may have reduced the beneficial impact of treatment.

Click to read the study in the Lancet

Dr. Alan Peaceman, MD, talks to 2 Minute Medicine: Northwestern University School of Medicine; Chief, Division of Obstetrics and Gynecology-Maternal Fetal Medicine.

“This randomized trial demonstrated that head cooling for encephalopathic infants with mild to moderate electroencephalography changes resulted in improved survival without severe neurologic disability at 18 months. Findings support the use of selective head cooling among those infants with hypoxemic-ischemic encephalopathy and less than severe EEG changes.”

In-Depth [randomized controlled trial]: A total of 234 term infants with moderate to severe neonatal encephalopathy and electroencephalography (EEG) changes were randomized to receive head cooling (n=116) or conventional care (n=118). Infants requiring high-dose anticonvulsants, those with major congenital anomalies, severe growth restriction or otherwise judged to be critically ill were excluded. Primary outcomes were death or severe neurodevelopmental disability at age 18 months.

Among infants with hypoxic-ischemic encephalopathy with mild-moderate EEG changes, those randomized to selective head cooling had significantly improved survival and lower risk of death or severe neurodevelopmental disability at 18 months (OR 0.47, CI 0.26-0.87, p = 0.02). The number needed to treat was 6 (CI 3-27). Infants with the most severe EEG changes did not derive benefit from head cooling (p = 0.51).

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