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Clinical features, diagnosis, and treatment of neonatal encephalopathy

Author
Yvonne Wu, MD, MPH
Section Editors
Douglas R Nordli, Jr, MD
Leonard E Weisman, MD
Deputy Editor
John F Dashe, MD, PhD

INTRODUCTION AND DEFINITION

Neonatal encephalopathy is a heterogeneous, clinically defined syndrome characterized by disturbed neurologic function in the earliest days of life in an infant born at or beyond 35 weeks of gestation, manifested by a reduced level of consciousness or seizures, and often accompanied by difficulty with initiating and maintaining respiration, and by depression of tone and reflexes [1].

This section will review the diagnosis, prognosis, and treatment of neonatal encephalopathy. The pathogenesis of neonatal encephalopathy is discussed elsewhere. (See "Etiology and pathogenesis of neonatal encephalopathy".)

ETIOLOGY

Neonatal encephalopathy can result from a wide variety of conditions and often remains unexplained. Birth asphyxia and hypoxic-ischemic (anoxic) encephalopathy are responsible for some, but not all, cases of neonatal encephalopathy. Given that the underlying nature of brain injury causing neurologic impairment in a newborn is often poorly understood, "neonatal encephalopathy" has emerged as the preferred term to describe the clinical syndrome of central nervous system dysfunction in the newborn period because it does not imply a specific underlying etiology or pathophysiology. (See "Etiology and pathogenesis of neonatal encephalopathy".)

EPIDEMIOLOGY

The incidence of neonatal encephalopathy depends on how the syndrome is defined, but published estimates vary between 2 and 9 per 1000 term births [2-5]. As the term "neonatal encephalopathy" became increasingly favored, it was shown in one US population that the diagnosis of "birth asphyxia" declined between the years 1991 and 2000 [2]. In a 2010 review, the estimated incidence of neonatal encephalopathy was 3.0 per 1000 live births (95% CI 2.7-3.3), while the estimated incidence of hypoxic-ischemic encephalopathy (a subset of neonatal encephalopathy) was 1.5 per 1000 live births (95% CI 1.3-1.7) [6].

CLINICAL PRESENTATION

The neonate who is encephalopathic may have an abnormal state of consciousness (eg, hyperalert, irritable, lethargic, or obtunded), diminished spontaneous movements, respiratory or feeding difficulties, poor tone, abnormal posturing, absent primitive reflexes, or seizure activity. In the delivery room, the infant will often exhibit low Apgar scores and a weak or absent cry. The severity of neonatal encephalopathy can be classified as mild, moderate, or severe according to these clinical findings, as discussed below. (See 'Clinical predictors' below.)

                   

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References
Top
  1. Executive summary: Neonatal encephalopathy and neurologic outcome, second edition. Report of the American College of Obstetricians and Gynecologists' Task Force on Neonatal Encephalopathy. Obstet Gynecol 2014; 123:896.
  2. Wu YW, Backstrand KH, Zhao S, et al. Declining diagnosis of birth asphyxia in California: 1991-2000. Pediatrics 2004; 114:1584.
  3. Graham EM, Ruis KA, Hartman AL, et al. A systematic review of the role of intrapartum hypoxia-ischemia in the causation of neonatal encephalopathy. Am J Obstet Gynecol 2008; 199:587.
  4. Thornberg E, Thiringer K, Odeback A, Milsom I. Birth asphyxia: incidence, clinical course and outcome in a Swedish population. Acta Paediatr 1995; 84:927.
  5. Lee AC, Kozuki N, Blencowe H, et al. Intrapartum-related neonatal encephalopathy incidence and impairment at regional and global levels for 2010 with trends from 1990. Pediatr Res 2013; 74 Suppl 1:50.
  6. Kurinczuk JJ, White-Koning M, Badawi N. Epidemiology of neonatal encephalopathy and hypoxic-ischaemic encephalopathy. Early Hum Dev 2010; 86:329.
  7. Chau V, Poskitt KJ, Miller SP. Advanced neuroimaging techniques for the term newborn with encephalopathy. Pediatr Neurol 2009; 40:181.
  8. Barnette AR, Horbar JD, Soll RF, et al. Neuroimaging in the evaluation of neonatal encephalopathy. Pediatrics 2014; 133:e1508.
  9. Redline RW. Severe fetal placental vascular lesions in term infants with neurologic impairment. Am J Obstet Gynecol 2005; 192:452.
  10. Ghei SK, Zan E, Nathan JE, et al. MR imaging of hypoxic-ischemic injury in term neonates: pearls and pitfalls. Radiographics 2014; 34:1047.
  11. Ferriero DM. Neonatal brain injury. N Engl J Med 2004; 351:1985.
  12. Barkovich AJ. MR and CT evaluation of profound neonatal and infantile asphyxia. AJNR Am J Neuroradiol 1992; 13:959.
  13. Roland EH, Poskitt K, Rodriguez E, et al. Perinatal hypoxic-ischemic thalamic injury: clinical features and neuroimaging. Ann Neurol 1998; 44:161.
  14. Miller SP, Ramaswamy V, Michelson D, et al. Patterns of brain injury in term neonatal encephalopathy. J Pediatr 2005; 146:453.
  15. Okereafor A, Allsop J, Counsell SJ, et al. Patterns of brain injury in neonates exposed to perinatal sentinel events. Pediatrics 2008; 121:906.
  16. Myers RE. Two patterns of perinatal brain damage and their conditions of occurrence. Am J Obstet Gynecol 1972; 112:246.
  17. Rutherford M, Ramenghi LA, Edwards AD, et al. Assessment of brain tissue injury after moderate hypothermia in neonates with hypoxic-ischaemic encephalopathy: a nested substudy of a randomised controlled trial. Lancet Neurol 2010; 9:39.
  18. Shankaran S, Barnes PD, Hintz SR, et al. Brain injury following trial of hypothermia for neonatal hypoxic-ischaemic encephalopathy. Arch Dis Child Fetal Neonatal Ed 2012; 97:F398.
  19. Bonifacio SL, Saporta A, Glass HC, et al. Therapeutic hypothermia for neonatal encephalopathy results in improved microstructure and metabolism in the deep gray nuclei. AJNR Am J Neuroradiol 2012; 33:2050.
  20. Cowan F, Rutherford M, Groenendaal F, et al. Origin and timing of brain lesions in term infants with neonatal encephalopathy. Lancet 2003; 361:736.
  21. Hankins GD, Speer M. Defining the pathogenesis and pathophysiology of neonatal encephalopathy and cerebral palsy. Obstet Gynecol 2003; 102:628.
  22. Miller SP, Newton N, Ferriero DM, et al. Predictors of 30-month outcome after perinatal depression: role of proton MRS and socioeconomic factors. Pediatr Res 2002; 52:71.
  23. Barnett A, Mercuri E, Rutherford M, et al. Neurological and perceptual-motor outcome at 5 - 6 years of age in children with neonatal encephalopathy: relationship with neonatal brain MRI. Neuropediatrics 2002; 33:242.
  24. Heinz ER, Provenzale JM. Imaging findings in neonatal hypoxia: a practical review. AJR Am J Roentgenol 2009; 192:41.
  25. Gano D, Sargent MA, Miller SP, et al. MRI findings in infants with infantile spasms after neonatal hypoxic-ischemic encephalopathy. Pediatr Neurol 2013; 49:401.
  26. Volpe JJ. Neonatal encephalopathy: an inadequate term for hypoxic-ischemic encephalopathy. Ann Neurol 2012; 72:156.
  27. Bydder GM, Rutherford MA. Diffusion-weighted imaging of the brain in neonates and infants. Magn Reson Imaging Clin N Am 2001; 9:83.
  28. Hope PL, Gould SJ, Howard S, et al. Precision of ultrasound diagnosis of pathologically verified lesions in the brains of very preterm infants. Dev Med Child Neurol 1988; 30:457.
  29. Shankaran S, Kottamasu SR, Kuhns L. Brain sonography, computed tomography, and single-photon emission computed tomography in term neonates with perinatal asphyxia. Clin Perinatol 1993; 20:379.
  30. Miller SP, Cozzio CC, Goldstein RB, et al. Comparing the diagnosis of white matter injury in premature newborns with serial MR imaging and transfontanel ultrasonography findings. AJNR Am J Neuroradiol 2003; 24:1661.
  31. Martin DJ, Hill A, Fitz CR, et al. Hypoxic/ischaemic cerebral injury in the neonatal brain. A report of sonographic features with computed tomographic correlation. Pediatr Radiol 1983; 13:307.
  32. Siegel MJ, Shackelford GD, Perlman JM, Fulling KH. Hypoxic-ischemic encephalopathy in term infants: diagnosis and prognosis evaluated by ultrasound. Radiology 1984; 152:395.
  33. Hill A. Current concepts of hypoxic-ischemic cerebral injury in the term newborn. Pediatr Neurol 1991; 7:317.
  34. Adsett DB, Fitz CR, Hill A. Hypoxic-ischaemic cerebral injury in the term newborn: correlation of CT findings with neurological outcome. Dev Med Child Neurol 1985; 27:155.
  35. Fitzhardinge PM, Flodmark O, Fitz CR, Ashby S. The prognostic value of computed tomography as an adjunct to assessment of the term infant with postasphyxial encephalopathy. J Pediatr 1981; 99:777.
  36. Graziani LJ, Pasto M, Stanley C, et al. Neonatal neurosonographic correlates of cerebral palsy in preterm infants. Pediatrics 1986; 78:88.
  37. Lupton BA, Hill A, Roland EH, et al. Brain swelling in the asphyxiated term newborn: pathogenesis and outcome. Pediatrics 1988; 82:139.
  38. Gluckman PD, Wyatt JS, Azzopardi D, et al. Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trial. Lancet 2005; 365:663.
  39. Volpe JJ. Hypoxic-ischemic encephalopathy: clinical aspects. In: Neurology of the Newborn, 5th, Volpe JJ (Ed), Saunders, Philadelphia 2008. p.400.
  40. Yager JY, Armstrong EA, Black AM. Treatment of the term newborn with brain injury: simplicity as the mother of invention. Pediatr Neurol 2009; 40:237.
  41. Committee on Fetus and Newborn, Papile LA, Baley JE, et al. Hypothermia and neonatal encephalopathy. Pediatrics 2014; 133:1146.
  42. Perlman M, Shah P. Time to adopt cooling for neonatal hypoxic-ischemic encephalopathy: response to a previous commentary. Pediatrics 2008; 121:616.
  43. Azzopardi D, Strohm B, Edwards AD, et al. Treatment of asphyxiated newborns with moderate hypothermia in routine clinical practice: how cooling is managed in the UK outside a clinical trial. Arch Dis Child Fetal Neonatal Ed 2009; 94:F260.
  44. Higgins RD, Raju T, Edwards AD, et al. Hypothermia and other treatment options for neonatal encephalopathy: an executive summary of the Eunice Kennedy Shriver NICHD workshop. J Pediatr 2011; 159:851.
  45. National Institute for Health and Clinial Excellence. IPG347. Therapeutic hypothermia with intracorporeal temperature monitoring for hypoxic perinatal brain injury. http://www.nice.org.uk/guidance/ipg347 (Accessed on August 19, 2014).
  46. Takenouchi T, Iwata O, Nabetani M, Tamura M. Therapeutic hypothermia for neonatal encephalopathy: JSPNM & MHLW Japan Working Group Practice Guidelines Consensus Statement from the Working Group on Therapeutic Hypothermia for Neonatal Encephalopathy, Ministry of Health, Labor and Welfare (MHLW), Japan, and Japan Society for Perinatal and Neonatal Medicine (JSPNM). Brain Dev 2012; 34:165.
  47. Wyckoff MH, Aziz K, Escobedo MB, et al. Part 13: Neonatal Resuscitation: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2015; 132:S543.
  48. Perlman JM, Wyllie J, Kattwinkel J, et al. Part 7: Neonatal Resuscitation: 2015 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. Circulation 2015; 132:S204.
  49. Tagin MA, Woolcott CG, Vincer MJ, et al. Hypothermia for neonatal hypoxic ischemic encephalopathy: an updated systematic review and meta-analysis. Arch Pediatr Adolesc Med 2012; 166:558.
  50. Jacobs SE, Berg M, Hunt R, et al. Cooling for newborns with hypoxic ischaemic encephalopathy. Cochrane Database Syst Rev 2013; :CD003311.
  51. Shankaran S, Laptook AR, Ehrenkranz RA, et al. Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N Engl J Med 2005; 353:1574.
  52. Azzopardi DV, Strohm B, Edwards AD, et al. Moderate hypothermia to treat perinatal asphyxial encephalopathy. N Engl J Med 2009; 361:1349.
  53. Simbruner G, Mittal RA, Rohlmann F, et al. Systemic hypothermia after neonatal encephalopathy: outcomes of neo.nEURO.network RCT. Pediatrics 2010; 126:e771.
  54. Jacobs SE, Morley CJ, Inder TE, et al. Whole-body hypothermia for term and near-term newborns with hypoxic-ischemic encephalopathy: a randomized controlled trial. Arch Pediatr Adolesc Med 2011; 165:692.
  55. Zhou WH, Cheng GQ, Shao XM, et al. Selective head cooling with mild systemic hypothermia after neonatal hypoxic-ischemic encephalopathy: a multicenter randomized controlled trial in China. J Pediatr 2010; 157:367.
  56. Gunn AJ, Gluckman PD, Gunn TR. Selective head cooling in newborn infants after perinatal asphyxia: a safety study. Pediatrics 1998; 102:885.
  57. Shankaran S, Laptook AR, Pappas A, et al. Effect of depth and duration of cooling on deaths in the NICU among neonates with hypoxic ischemic encephalopathy: a randomized clinical trial. JAMA 2014; 312:2629.
  58. Shankaran S, Pappas A, McDonald SA, et al. Childhood outcomes after hypothermia for neonatal encephalopathy. N Engl J Med 2012; 366:2085.
  59. Azzopardi D, Strohm B, Marlow N, et al. Effects of hypothermia for perinatal asphyxia on childhood outcomes. N Engl J Med 2014; 371:140.
  60. Wyatt JS, Gluckman PD, Liu PY, et al. Determinants of outcomes after head cooling for neonatal encephalopathy. Pediatrics 2007; 119:912.
  61. Laptook A, Tyson J, Shankaran S, et al. Elevated temperature after hypoxic-ischemic encephalopathy: risk factor for adverse outcomes. Pediatrics 2008; 122:491.
  62. Laptook AR, McDonald SA, Shankaran S, et al. Elevated temperature and 6- to 7-year outcome of neonatal encephalopathy. Ann Neurol 2013; 73:520.
  63. Rossouw G, Irlam J, Horn AR. Therapeutic hypothermia for hypoxic ischaemic encephalopathy using low-technology methods: a systematic review and meta-analysis. Acta Paediatr 2015; 104:1217.
  64. Papile LA. Systemic hypothermia--a "cool" therapy for neonatal hypoxic-ischemic encephalopathy. N Engl J Med 2005; 353:1619.
  65. Higgins RD, Raju TN, Perlman J, et al. Hypothermia and perinatal asphyxia: executive summary of the National Institute of Child Health and Human Development workshop. J Pediatr 2006; 148:170.
  66. Blackmon LR, Stark AR, American Academy of Pediatrics Committee on Fetus and Newborn. Hypothermia: a neuroprotective therapy for neonatal hypoxic-ischemic encephalopathy. Pediatrics 2006; 117:942.
  67. Strohm B, Hobson A, Brocklehurst P, et al. Subcutaneous fat necrosis after moderate therapeutic hypothermia in neonates. Pediatrics 2011; 128:e450.
  68. Woods AG, Cederholm CK. Subcutaneous fat necrosis and whole-body cooling therapy for neonatal encephalopathy. Adv Neonatal Care 2012; 12:345.
  69. Rangarajan V, Juul SE. Erythropoietin: emerging role of erythropoietin in neonatal neuroprotection. Pediatr Neurol 2014; 51:481.
  70. Zhu C, Kang W, Xu F, et al. Erythropoietin improved neurologic outcomes in newborns with hypoxic-ischemic encephalopathy. Pediatrics 2009; 124:e218.
  71. Wu YW, Mathur AM, Chang T, et al. High-Dose Erythropoietin and Hypothermia for Hypoxic-Ischemic Encephalopathy: A Phase II Trial. Pediatrics 2016; 137.
  72. Tan WK, Williams CE, Gunn AJ, et al. Pretreatment with monosialoganglioside GM1 protects the brain of fetal sheep against hypoxic-ischemic injury without causing systemic compromise. Pediatr Res 1993; 34:18.
  73. Han BH, D'Costa A, Back SA, et al. BDNF blocks caspase-3 activation in neonatal hypoxia-ischemia. Neurobiol Dis 2000; 7:38.
  74. Robertson C, Finer N. Term infants with hypoxic-ischemic encephalopathy: outcome at 3.5 years. Dev Med Child Neurol 1985; 27:473.
  75. Robertson CM, Finer NN, Grace MG. School performance of survivors of neonatal encephalopathy associated with birth asphyxia at term. J Pediatr 1989; 114:753.
  76. Finer NN, Robertson CM, Richards RT, et al. Hypoxic-ischemic encephalopathy in term neonates: perinatal factors and outcome. J Pediatr 1981; 98:112.
  77. Levene ML, Kornberg J, Williams TH. The incidence and severity of post-asphyxial encephalopathy in full-term infants. Early Hum Dev 1985; 11:21.
  78. van Handel M, Swaab H, de Vries LS, Jongmans MJ. Long-term cognitive and behavioral consequences of neonatal encephalopathy following perinatal asphyxia: a review. Eur J Pediatr 2007; 166:645.
  79. Pappas A, Shankaran S, McDonald SA, et al. Cognitive outcomes after neonatal encephalopathy. Pediatrics 2015; 135:e624.
  80. Sarnat HB, Sarnat MS. Neonatal encephalopathy following fetal distress. A clinical and electroencephalographic study. Arch Neurol 1976; 33:696.
  81. Shankaran S, Woldt E, Koepke T, et al. Acute neonatal morbidity and long-term central nervous system sequelae of perinatal asphyxia in term infants. Early Hum Dev 1991; 25:135.
  82. Lacey JL, Henderson-Smart DJ. Assessment of preterm infants in the intensive-care unit to predict cerebral palsy and motor outcome at 6 years. Dev Med Child Neurol 1998; 40:310.
  83. Thompson CM, Puterman AS, Linley LL, et al. The value of a scoring system for hypoxic ischaemic encephalopathy in predicting neurodevelopmental outcome. Acta Paediatr 1997; 86:757.
  84. Shah PS, Beyene J, To T, et al. Postasphyxial hypoxic-ischemic encephalopathy in neonates: outcome prediction rule within 4 hours of birth. Arch Pediatr Adolesc Med 2006; 160:729.
  85. Glass HC, Hong KJ, Rogers EE, et al. Risk factors for epilepsy in children with neonatal encephalopathy. Pediatr Res 2011; 70:535.
  86. Kwon JM, Guillet R, Shankaran S, et al. Clinical seizures in neonatal hypoxic-ischemic encephalopathy have no independent impact on neurodevelopmental outcome: secondary analyses of data from the neonatal research network hypothermia trial. J Child Neurol 2011; 26:322.
  87. Gunn AJ, Wyatt JS, Whitelaw A, et al. Therapeutic hypothermia changes the prognostic value of clinical evaluation of neonatal encephalopathy. J Pediatr 2008; 152:55.
  88. Thoresen M, Hellström-Westas L, Liu X, de Vries LS. Effect of hypothermia on amplitude-integrated electroencephalogram in infants with asphyxia. Pediatrics 2010; 126:e131.
  89. Shankaran S, Laptook AR, Tyson JE, et al. Evolution of encephalopathy during whole body hypothermia for neonatal hypoxic-ischemic encephalopathy. J Pediatr 2012; 160:567.
  90. Martinez-Biarge M, Diez-Sebastian J, Kapellou O, et al. Predicting motor outcome and death in term hypoxic-ischemic encephalopathy. Neurology 2011; 76:2055.
  91. Alderliesten T, de Vries LS, Benders MJ, et al. MR imaging and outcome of term neonates with perinatal asphyxia: value of diffusion-weighted MR imaging and ¹H MR spectroscopy. Radiology 2011; 261:235.
  92. van Laerhoven H, de Haan TR, Offringa M, et al. Prognostic tests in term neonates with hypoxic-ischemic encephalopathy: a systematic review. Pediatrics 2013; 131:88.
  93. Massaro AN. MRI for neurodevelopmental prognostication in the high-risk term infant. Semin Perinatol 2015; 39:159.
  94. Steinman KJ, Gorno-Tempini ML, Glidden DV, et al. Neonatal watershed brain injury on magnetic resonance imaging correlates with verbal IQ at 4 years. Pediatrics 2009; 123:1025.
  95. Wu YW, Croen LA, Shah SJ, et al. Cerebral palsy in a term population: risk factors and neuroimaging findings. Pediatrics 2006; 118:690.
  96. Barkovich AJ, Hajnal BL, Vigneron D, et al. Prediction of neuromotor outcome in perinatal asphyxia: evaluation of MR scoring systems. AJNR Am J Neuroradiol 1998; 19:143.
  97. Massaro AN, Kadom N, Chang T, et al. Quantitative analysis of magnetic resonance images and neurological outcome in encephalopathic neonates treated with whole-body hypothermia. J Perinatol 2010; 30:596.
  98. Barkovich AJ, Miller SP, Bartha A, et al. MR imaging, MR spectroscopy, and diffusion tensor imaging of sequential studies in neonates with encephalopathy. AJNR Am J Neuroradiol 2006; 27:533.
  99. Corbo ET, Bartnik-Olson BL, Machado S, et al. The effect of whole-body cooling on brain metabolism following perinatal hypoxic-ischemic injury. Pediatr Res 2012; 71:85.
  100. Cheong JL, Coleman L, Hunt RW, et al. Prognostic utility of magnetic resonance imaging in neonatal hypoxic-ischemic encephalopathy: substudy of a randomized trial. Arch Pediatr Adolesc Med 2012; 166:634.
  101. Inder TE, Hunt RW, Morley CJ, et al. Randomized trial of systemic hypothermia selectively protects the cortex on MRI in term hypoxic-ischemic encephalopathy. J Pediatr 2004; 145:835.
  102. Azzopardi D, Edwards AD. Magnetic resonance biomarkers of neuroprotective effects in infants with hypoxic ischemic encephalopathy. Semin Fetal Neonatal Med 2010; 15:261.
  103. Rutherford MA, Pennock JM, Counsell SJ, et al. Abnormal magnetic resonance signal in the internal capsule predicts poor neurodevelopmental outcome in infants with hypoxic-ischemic encephalopathy. Pediatrics 1998; 102:323.
  104. de Vries LS, Jongmans MJ. Long-term outcome after neonatal hypoxic-ischaemic encephalopathy. Arch Dis Child Fetal Neonatal Ed 2010; 95:F220.
  105. Perez A, Ritter S, Brotschi B, et al. Long-term neurodevelopmental outcome with hypoxic-ischemic encephalopathy. J Pediatr 2013; 163:454.
  106. Harteman JC, Groenendaal F, Toet MC, et al. Diffusion-weighted imaging changes in cerebral watershed distribution following neonatal encephalopathy are not invariably associated with an adverse outcome. Dev Med Child Neurol 2013; 55:642.
  107. Bonifacio SL, Glass HC, Vanderpluym J, et al. Perinatal events and early magnetic resonance imaging in therapeutic hypothermia. J Pediatr 2011; 158:360.
  108. Robertson RL, Ben-Sira L, Barnes PD, et al. MR line-scan diffusion-weighted imaging of term neonates with perinatal brain ischemia. AJNR Am J Neuroradiol 1999; 20:1658.
  109. Amess PN, Penrice J, Wylezinska M, et al. Early brain proton magnetic resonance spectroscopy and neonatal neurology related to neurodevelopmental outcome at 1 year in term infants after presumed hypoxic-ischaemic brain injury. Dev Med Child Neurol 1999; 41:436.
  110. Hanrahan JD, Cox IJ, Azzopardi D, et al. Relation between proton magnetic resonance spectroscopy within 18 hours of birth asphyxia and neurodevelopment at 1 year of age. Dev Med Child Neurol 1999; 41:76.
  111. Boichot C, Walker PM, Durand C, et al. Term neonate prognoses after perinatal asphyxia: contributions of MR imaging, MR spectroscopy, relaxation times, and apparent diffusion coefficients. Radiology 2006; 239:839.
  112. Thayyil S, Chandrasekaran M, Taylor A, et al. Cerebral magnetic resonance biomarkers in neonatal encephalopathy: a meta-analysis. Pediatrics 2010; 125:e382.
  113. Shanmugalingam S, Thornton JS, Iwata O, et al. Comparative prognostic utilities of early quantitative magnetic resonance imaging spin-spin relaxometry and proton magnetic resonance spectroscopy in neonatal encephalopathy. Pediatrics 2006; 118:1467.
  114. Boardman JP, Ganesan V, Rutherford MA, et al. Magnetic resonance image correlates of hemiparesis after neonatal and childhood middle cerebral artery stroke. Pediatrics 2005; 115:321.
  115. Mercuri E, Rutherford M, Cowan F, et al. Early prognostic indicators of outcome in infants with neonatal cerebral infarction: a clinical, electroencephalogram, and magnetic resonance imaging study. Pediatrics 1999; 103:39.
  116. Lee J, Croen LA, Lindan C, et al. Predictors of outcome in perinatal arterial stroke: a population-based study. Ann Neurol 2005; 58:303.
  117. Takeuchi T, Watanabe K. The EEG evolution and neurological prognosis of neonates with perinatal hypoxia [corrected]. Brain Dev 1989; 11:115.
  118. Holmes GL, Lombroso CT. Prognostic value of background patterns in the neonatal EEG. J Clin Neurophysiol 1993; 10:323.
  119. Biagioni E, Mercuri E, Rutherford M, et al. Combined use of electroencephalogram and magnetic resonance imaging in full-term neonates with acute encephalopathy. Pediatrics 2001; 107:461.
  120. Pezzani C, Radvanyi-Bouvet MF, Relier JP, Monod N. Neonatal electroencephalography during the first twenty-four hours of life in full-term newborn infants. Neuropediatrics 1986; 17:11.
  121. Pressler RM, Boylan GB, Morton M, et al. Early serial EEG in hypoxic ischaemic encephalopathy. Clin Neurophysiol 2001; 112:31.
  122. van Rooij LG, Toet MC, Osredkar D, et al. Recovery of amplitude integrated electroencephalographic background patterns within 24 hours of perinatal asphyxia. Arch Dis Child Fetal Neonatal Ed 2005; 90:F245.
  123. Ramaswamy V, Horton J, Vandermeer B, et al. Systematic review of biomarkers of brain injury in term neonatal encephalopathy. Pediatr Neurol 2009; 40:215.
  124. Massaro AN, Chang T, Kadom N, et al. Biomarkers of brain injury in neonatal encephalopathy treated with hypothermia. J Pediatr 2012; 161:434.
  125. Ennen CS, Huisman TA, Savage WJ, et al. Glial fibrillary acidic protein as a biomarker for neonatal hypoxic-ischemic encephalopathy treated with whole-body cooling. Am J Obstet Gynecol 2011; 205:251.e1.
  126. Massaro AN, Jeromin A, Kadom N, et al. Serum biomarkers of MRI brain injury in neonatal hypoxic ischemic encephalopathy treated with whole-body hypothermia: a pilot study. Pediatr Crit Care Med 2013; 14:310.
  127. Chalak LF, Sánchez PJ, Adams-Huet B, et al. Biomarkers for severity of neonatal hypoxic-ischemic encephalopathy and outcomes in newborns receiving hypothermia therapy. J Pediatr 2014; 164:468.