Mild Neonatal Encephalopathy—How, When, and How Much to Treat?

There is compelling evidence from randomized clinical trials that therapeutic hypothermia for full term or near-term neonates with moderate to severe hypoxic-ischemic encephalopathy (HIE) improves survival without disability.¹ However, more than half of all infants with HIE have mild encephalopathy,² as shown by hyperalertness, agitation and hypertonia. These infants were not enrolled in the clinical trials because of their apparently lower risk for adverse outcomes, and so they do not meet current criteria for treatment. However, there is increasing evidence that infants who have mild encephalopathy in the first 6 hours of life may still have a high risk for brain injury. For example, in a level 3 cohort, 54% of 48 cases of mild HIE had cerebral abnormalities on magnetic resonance imaging.³ Consistent with this, in a prospective cohort study of infants who were not treated with therapeutic hypothermia, cases with mild HIE determined by both early electroencephalography and clinical examination had adverse cognitive and neuromotor outcomes at 5 years of age compared with healthy control infants.² Although intact survival was greater after mild than moderate or severe HIE, among survivors, there was no significant difference in the cognitive outcomes of infants who had mild or moderate HIE. This finding contrasts with historical observations that infants with mild encephalopathy had normal neurodevelopmental outcomes.⁴