MRI and Withdrawal of Life Support From Newborn Infants With Hypoxic-Ischemic Encephalopathy

The majority of deaths in infants with hypoxic-ischemic encephalopathy (HIE) follow decisions to withdraw life-sustaining treatment. Clinicians use prognostic tests including MRI to help determine prognosis and decide whether to consider treatment withdrawal. A recently published meta-analysis provided valuable information on the prognostic utility of magnetic resonance (MR) biomarkers in HIE and suggested, in particular, that proton MR spectroscopy is the most accurate predictor of neurodevelopmental outcome. How should this evidence influence treatment-limitation decisions? In this article I outline serious limitations in existing prognostic studies of HIE, including small sample size, selectionbias, vagueandoverly inclusive outcomeassessment, andpotential self-fulfilling prophecies. Such limitations make it difficult to answer the most important prognostic question. Reanalysis of published data reveals that severe abnormalities on conventional MRI in the first week have a sensitivity of 71% (95% confidence interval: 59%–91%) and specificity of 84% (95% confidence interval: 68%–93%) for very adverse outcome in infants withmoderate encephalopathy. On current evidence, MR biomarkers alone are not sufficiently accurate to direct treatment-limitation decisions. Although there may be a role for using MRI or MR spectroscopy in combination with other prognostic markers to identify infants with very adverse outcome, it is not possible frommeta-analysis to define this group clearly. There is anurgent need for improvedprognostic research intoHIE. Pediatrics 2010;126:e451–e458 Hypoxic-ischemic encephalopathy (HIE) is amajor contributor to global child mortality and morbidity.1 Although therapeutic hypothermia has recently emerged as a means of neuroprotection for infants with HIE, many infants still have an adverse outcome. Almost 50% of infants enrolled in recent trials and treated with hypothermia either died or were found to have severe disability at the 18-month follow-up.2,3 In developed countries the majority of deaths of infants with HIE follow decisions to withdraw life-sustaining treatment.4,5 Two-thirds of the deaths in the recent cooling trials followed treatment withdrawal.3,6 One important factor that clinicians use in making such decisions is the severity of encephalopathy. In particular, infants with severe (Sarnat stage 3)7 encephalopathy are generally believed to have a uniformly dire prognosis.8,9 However, prognostication in infants with moderate encephalopathy is more difficult.9–11 A variety of clinical, electrophysiological, and radiologic tools have been used to help prognosticate.9 In particular, MRI has emerged as potentially one of the most useful tools for prognostication in HIE,8,12–14 and it has been recommended that all infants with HIE have an MRI performed between AUTHOR: AUTHOR: Dominic Wilkinson, MBBS, BMedSci, MBioeth, FRACP Ethox Centre, Department of Public Health and Primary Health Care, and Oxford Uehiro Centre for Practical Ethics, University of Oxford, Headington, United Kingdom