Evolution of Amplitude-Integrated Electroencephalogram as a Predictor of Outcome in Term Encephalopathic Neonates Receiving Therapeutic Hypothermia
31 May 2017
28 August 2017
28 September 2017 (eFirst)
Objectives This study aims to evaluate the ability of (1) a novel amplitude-integrated electroencephalogram (aEEG) background evolution classification system; and (2) specific hour of life (HOL) cut points when observation of aEEG normalization and development of cycling can predict adverse neurological outcomes in infants with hypoxic–ischemic encephalopathy (HIE).
Study Design Continuous aEEG data of term neonates with HIE were reviewed for background pattern and aEEG cycling from start of monitoring through rewarming. Infants were classified by overall background evolution pattern. Adverse outcomes were defined as death or severe magnetic resonance imaging injury, as well as developmental outcomes in a subset of patients. aEEG characteristics were compared between outcome groups by multivariate regression models, likelihood ratios (LR), and receiver operating characteristic (ROC) curve analyses.
Results Overall, 80 infants receiving therapeutic hypothermia met the inclusion criteria. Background evolution pattern seemed to distinguish outcome groups more reliably than background pattern at discrete intervals in time (LR: 43.9, p value < 0.001). Infants who did not reach discontinuous background by 15.5 HOL, cycling by 45.5 HOL, and normalization by 78 HOL were most likely to have adverse outcomes.
Conclusion Evolution of aEEG in term neonates with HIE may be more useful for predicting outcome than evaluating aEEG at discrete intervals in time.
Keywordshypoxic–ischemic encephalopathy - monitoring - brain injury - magnetic resonance imaging - neurodevelopmental outcome
This work was supported by the Clinical and Translational Science Institute at Children's National (UL1TR000075, 1KL2RR031987–01) and the Intellectual and Developmental Disabilities Research Consortium (NIH P30HD040677).
* Current affiliation of Dr. Sewell is Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, Georgia.
- 1 Kleinman ME, de Caen AR, Chameides L. , et al; Pediatric Basic and Advanced Life Support Chapter Collaborators. Pediatric basic and advanced life support: 2010 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science with Treatment Recommendations. Pediatrics 2010; 126 (05) e1261-e1318
- 2 Higgins RD, Raju T, Edwards AD. , et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Hypothermia Workshop Speakers and Moderators. Hypothermia and other treatment options for neonatal encephalopathy: an executive summary of the Eunice Kennedy Shriver NICHD workshop. J Pediatr 2011; 159 (05) 851-858.e1
- 3 Jacobs SE, Berg M, Hunt R, Tarnow-Mordi WO, Inder TE, Davis PG. Cooling for newborns with hypoxic ischaemic encephalopathy. Cochrane Database Syst Rev 2013; 1 (01) CD003311
- 4 Massaro AN, Tsuchida T, Kadom N. , et al. aEEG evolution during therapeutic hypothermia and prediction of NICU outcome in encephalopathic neonates. Neonatology 2012; 102 (03) 197-202
- 5 Bonifacio SL, deVries LS, Groenendaal F. Impact of hypothermia on predictors of poor outcome: how do we decide to redirect care?. Semin Fetal Neonatal Med 2015; 20 (02) 122-127
- 6 Hellström-Westas L, Rosén I, Svenningsen NW. Predictive value of early continuous amplitude integrated EEG recordings on outcome after severe birth asphyxia in full term infants. Arch Dis Child Fetal Neonatal Ed 1995; 72 (01) F34-F38
- 7 Toet MC, Hellström-Westas L, Groenendaal F, Eken P, de Vries LS. Amplitude integrated EEG 3 and 6 hours after birth in full term neonates with hypoxic-ischaemic encephalopathy. Arch Dis Child Fetal Neonatal Ed 1999; 81 (01) F19-F23
- 8 Thoresen M, Hellström-Westas L, Liu X, de Vries LS. Effect of hypothermia on amplitude-integrated electroencephalogram in infants with asphyxia. Pediatrics 2010; 126 (01) e131-e139
- 9 Azzopardi D. ; TOBY study group. Predictive value of the amplitude integrated EEG in infants with hypoxic ischaemic encephalopathy: data from a randomised trial of therapeutic hypothermia. Arch Dis Child Fetal Neonatal Ed 2014; 99 (01) F80-F82
- 10 Sarkar S, Barks JD, Donn SM. Should amplitude-integrated electroencephalography be used to identify infants suitable for hypothermic neuroprotection?. J Perinatol 2008; 28 (02) 117-122
- 11 Hallberg B, Grossmann K, Bartocci M, Blennow M. The prognostic value of early aEEG in asphyxiated infants undergoing systemic hypothermia treatment. Acta Paediatr 2010; 99 (04) 531-536
- 12 Csekő AJ, Bangó M, Lakatos P, Kárdási J, Pusztai L, Szabó M. Accuracy of amplitude-integrated electroencephalography in the prediction of neurodevelopmental outcome in asphyxiated infants receiving hypothermia treatment. Acta Paediatr 2013; 102 (07) 707-711
- 13 Gunn AJ, Wyatt JS, Whitelaw A. , et al; CoolCap Study Group. Therapeutic hypothermia changes the prognostic value of clinical evaluation of neonatal encephalopathy. J Pediatr 2008; 152 (01) 55-58, 58.e1
- 14 Shankaran S, Laptook AR, Tyson JE. , et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Evolution of encephalopathy during whole body hypothermia for neonatal hypoxic-ischemic encephalopathy. J Pediatr 2012; 160 (04) 567-572.e3
- 15 Shankaran S, Laptook AR, Ehrenkranz RA. , et al; National Institute of Child Health and Human Development Neonatal Research Network. Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N Engl J Med 2005; 353 (15) 1574-1584
- 16 Sarnat HB, Sarnat MS. Neonatal encephalopathy following fetal distress. A clinical and electroencephalographic study. Arch Neurol 1976; 33 (10) 696-705
- 17 Prior PF, Maynard DE. Monitoring Cerebral Function: Long-Term Monitoring of EEG and Evoked Potentials. New York, NY: Elsevier; 1986
- 18 Barkovich AJ, Hajnal BL, Vigneron D. , et al. Prediction of neuromotor outcome in perinatal asphyxia: evaluation of MR scoring systems. Am J Neuroradiol 1998; 19 (01) 143-149
- 19 Black MM, Matula K. Essentials of Bayley Scales of Infant Development–II Assessment (vol. 5). New York, NY: John Wiley & Sons Incorporated; 2000
- 20 Bayley N. Bayley Scales of Infant and Toddler Development. 3rd ed. San Antonio, TX: Harcourt Assessment; 2006
- 21 Anderson PJ, De Luca CR, Hutchinson E, Roberts G, Doyle LW. ; Victorian Infant Collaborative Group. Underestimation of developmental delay by the new Bayley-III Scale. Arch Pediatr Adolesc Med 2010; 164 (04) 352-356
- 22 Vohr BR, Stephens BE, Higgins RD. , et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Are outcomes of extremely preterm infants improving? Impact of Bayley assessment on outcomes. J Pediatr 2012; 161 (02) 222-8.e3
- 23 Chalak LF, DuPont TL, Sánchez PJ. , et al. Neurodevelopmental outcomes after hypothermia therapy in the era of Bayley-III. J Perinatol 2014; 34 (08) 629-633
- 24 Del Río R, Ochoa C, Alarcon A, Arnáez J, Blanco D, García-Alix A. Amplitude integrated electroencephalogram as a prognostic tool in neonates with hypoxic-ischemic encephalopathy: a systematic review. PLoS One 2016; 11 (11) e0165744
- 25 Tsuchida TN, Wusthoff CJ, Shellhaas RA. , et al; American Clinical Neurophysiology Society Critical Care Monitoring Committee. American clinical neurophysiology society standardized EEG terminology and categorization for the description of continuous EEG monitoring in neonates: report of the American Clinical Neurophysiology Society critical care monitoring committee. J Clin Neurophysiol 2013; 30 (02) 161-173
- 26 Tsuchida TN. EEG background patterns and prognostication of neonatal encephalopathy in the era of hypothermia. J Clin Neurophysiol 2013; 30 (02) 122-125
- 27 Shankaran S, Barnes PD, Hintz SR. , et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Brain injury following trial of hypothermia for neonatal hypoxic-ischaemic encephalopathy. Arch Dis Child Fetal Neonatal Ed 2012; 97 (06) F398-F404
- 28 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 (01) 39-45