Elsevier

Clinical Neurophysiology

Volume 127, Issue 1, January 2016, Pages 285-296
Clinical Neurophysiology

EEG background features that predict outcome in term neonates with hypoxic ischaemic encephalopathy: A structured review

https://doi.org/10.1016/j.clinph.2015.05.018Get rights and content

Highlights

  • Classification of HIE is important as a selection criterion for hypothermia treatment.

  • Background features of EEG predict neurodevelopmental outcome.

  • Definitions of EEG background features needs agreement.

Abstract

Objectives

Hypoxic ischaemic encephalopathy is a significant cause of mortality and morbidity in the term infant. Electroencephalography (EEG) is a useful tool in the assessment of newborns with HIE. This systematic review of published literature identifies those background features of EEG in term neonates with HIE that best predict neurodevelopmental outcome.

Methods

A literature search was conducted using the PubMed, EMBASE and CINAHL databases from January 1960 to April 2014. Studies included in the review described recorded EEG background features, neurodevelopmental outcomes at a minimum age of 12 months and were published in English. Pooled sensitivities and specificities of EEG background features were calculated and meta-analyses were performed for each background feature.

Results

Of the 860 articles generated by the initial search strategy, 52 studies were identified as potentially relevant. Twenty-one studies were excluded as they did not distinguish between different abnormal background features, leaving 31 studies from which data were extracted for the meta-analysis. The most promising neonatal EEG features are: burst suppression (sensitivity 0.87 [95% CI (0.78–0.92)]; specificity 0.82 [95% CI (0.72–0.88)]), low voltage (sensitivity 0.92 [95% CI (0.72–0.97)]; specificity 0.99 [95% CI (0.88–1.0)]), and flat trace (sensitivity 0.78 [95% CI (0.58–0.91)]; specificity 0.99 [95% CI (0.88–1.0)]).

Conclusion

Burst suppression, low voltage and flat trace in the EEG of term neonates with HIE most accurately predict long term neurodevelopmental outcome.

Significance

This structured review and meta-analysis provides quality evidence of the background EEG features that best predict neurodevelopmental outcome.

Introduction

Hypoxic ischaemic encephalopathy (HIE) occurs following a peripartum hypoxic–ischaemic insult to the brain. A secondary energy failure follows, with build-up of reactive metabolites and injury ensues (Volpe, 2008). In the term newborn, HIE occurs in 1 to 3 per 1000 live full-term births (Lai and Yang, 2011) and causes 23% of the 3.6 million neonatal deaths that occur globally (Lawn et al., 2010). The spectrum of long-term morbidity in survivors ranges from mild motor and cognitive deficits to cerebral palsy and severe cognitive deficits (Perlman and Shah, 2011). The outcomes of HIE or “birth asphyxia” can be devastating and permanent, making it a major burden for the patient, the family and society (Lai and Yang, 2011). The ability to accurately predict outcomes in this population is important in identifying those most appropriate to enrol in studies of neuroprotective or neurorestorative therapies.

Electroencephalography (EEG) is a useful method of assessment in asphyxiated infants. Conventional and amplitude integrated EEG (aEEG) both perform well in predicting outcome (van Laerhoven et al., 2013) and in the early diagnosis and classification of HIE severity (Walsh et al., 2011). The benefits of EEG are that it can easily be implemented at the cot-side soon after birth and it provides a real-time measure of cerebral function (Walsh et al., 2011). Detecting seizures (Navakatikyan et al., 2006, Bjorkman et al., 2010, Boashash et al., 2013) and assessing response to anticonvulsants (Hamelin et al., 2011) are other useful functions of EEG recording in the clinical setting, particularly because many seizures in the newborn have no detectable clinical manifestations. A normal EEG is highly predictive of a normal outcome, whereas various abnormal EEG features have been consistently associated with neurological abnormalities or death (Hamelin et al., 2011). We conducted a systematic review and meta-analysis of the literature to determine which specific background features of the EEG, in term neonates with HIE, best predict outcome.

Section snippets

Search strategy and inclusion and exclusion criteria

A literature search was conducted of the PubMed, EMBASE and CINAHL databases for studies published between January 1960 and April 2014. The search terms HIE or asphyxia, EEG, term newborn infants, prognosis or outcomes; and their derivatives were used to locate relevant studies. For PubMed, the specific search was: (((“Asphyxia Neonatorum” [Mesh] OR asphyx[tiab]) OR Hypoxic Ischemic Encephalopathy OR sarnat[tiab])) AND (((Term OR Neonate OR newborn OR neonat) AND (Electroencephalo OR

Results

Of the 860 articles generated by the initial search strategy, 566 studies remained when duplicates were removed. In the first stage, only 48 studies remained after hand-searching for the presence of reporting of EEG background features along with neurodevelopmental outcome in term neonates with HIE. A further 4 more were identified through hand-searching the references contained in the 48 studies. A total of 52 studies were finally identified. A further 21 studies were excluded because they did

Discussion

We have performed a meta-analysis to establish the prognostic value of different EEG background patterns in term neonates with HIE. To our knowledge this is the first review to analyse systematically different EEG techniques (CFM, aEEG, cEEG, international 10–20 EEG) and the background activity as a predictor of neurodevelopmental outcome. The meta-analysis clearly indicates that some features of EEG predict outcome accurately in term neonates with HIE.

One channel (CFM) or two channel (aEEG)

Conclusion

Background features of EEG accurately predict long term neurodevelopmental outcome in term neonates with HIE. These results have been generated in studies of term neonates and further studies are needed to determine the usefulness of EEG background patterns for prognostication of outcome in preterm infants.

The studies reviewed here are from different decades covering the change from analogue to digital EEG equipment. However, we are interested in the ability of EEG background patterns in term

Acknowledgements

Lars Eriksson and Nicola Foxlee, librarians at The University of Queensland Health Science Library provided assistance in defining the search strategy. Dr. Robert Ware, senior biostatistical consultant, School of Population Health, The University of Queensland provided statistical assistance. This work was supported in part by a Grant from the Qatar National Research Fund under its National Priorities Research Program award number NPRP 6-885-2-364.

Conflict of interest: None

References (92)

  • J.S. Hahn et al.

    Interburst interval measurements in the EEGs of premature infants with normal neurological outcome

    Electroencephalogr Clin Neurophysiol

    (1989)
  • S. Hamelin et al.

    Influence of hypothermia on the prognostic value of early EEG in full-term neonates with hypoxic ischemic encephalopathy

    Clin Neurophysiol

    (2011)
  • G. Holmes et al.

    Prognostic value of the electroencephalogram in neonatal asphyxia

    Electroencephalogr Clin Neurophysiol

    (1982)
  • M.S. Khlif et al.

    Effective implementation of time–frequency matched filter with adapted pre and postprocessing for data-dependent detection of newborn seizures

    Med Eng Phys

    (2013)
  • J.E. Lawn et al.

    3.6 million neonatal deaths—what is progressing and what is not?

    Semin Perinatol

    (2010)
  • E. Mariani et al.

    Prognostic value of electroencephalograms in asphyxiated newborns treated with hypothermia

    Pediatr Neurol

    (2008)
  • C.C. Menache et al.

    Prognostic value of neonatal discontinuous EEG

    Pediatr Neurol

    (2002)
  • M.A. Navakatikyan et al.

    Seizure detection algorithm for neonates based on wave-sequence analysis

    Clin Neurophysiol

    (2006)
  • M. Perlman et al.

    Hypoxic–ischemic encephalopathy: challenges in outcome and prediction

    J Pediatr

    (2011)
  • F. Pisani et al.

    Epilepsy after neonatal seizures: literature review

    Eur J Paediatr Neurol

    (2015)
  • M. Polat et al.

    Prediction of neurodevelopmental outcome in term neonates with hypoxic–ischemic encephalopathy

    Eur J Paediatr Neurol

    (2013)
  • H.F. Prechtl et al.

    Predictive value of general movements in asphyxiated fullterm infants

    Early Hum Dev

    (1993)
  • R. Pressler et al.

    Early serial EEG in hypoxic ischaemic encephalopathy

    Clin Neurophysiol

    (2001)
  • E. Shany et al.

    Predictive value of amplitude-integrated electroencephalography pattern and voltage in asphyxiated term infants

    Pediatr Neurol

    (2006)
  • R.A. Shellhaas et al.

    Assessment of neonatal electroencephalography (EEG) background by conventional and two amplitude-integrated EEG classification systems

    J Pediatr

    (2008)
  • D. Sinclair et al.

    EEG and long-term outcome of term infants with neonatal hypoxic–ischemic encephalopathy

    Clin Neurophysiol

    (1999)
  • T. Takeuchi et al.

    The EEG evolution and neurological prognosis of perinatal hypoxia neonates

    Brain Dev

    (1989)
  • B.H. Walsh et al.

    The use of conventional EEG for the assessment of hypoxic ischaemic encephalopathy in the newborn: a review

    Clin Neurophysiol

    (2011)
  • K. Watanabe et al.

    Behavioral state cycles, background EEGs and prognosis of newborns with perinatal hypoxia

    Electroencephalogr Clin Neurophysiol

    (1980)
  • E. Zeinstra et al.

    The prognostic value of serial EEG recordings following acute neonatal asphyxia in full-term infants

    Eur J Paediatr Neurol

    (2001)
  • N.S. Abend et al.

    EEG monitoring during therapeutic hypothermia in neonates, children, and adults

    Am J Electroneurodiagnostic Technol

    (2011)
  • N. al Naqeeb et al.

    Assessment of neonatal encephalopathy by amplitude-integrated electroencephalography

    Pediatrics

    (1999)
  • C. Amiel-Tison et al.

    Neurological development from birth to six years: guide for examination and evaluation

    (2001)
  • G. Ancora et al.

    Early predictors of short term neurodevelopmental outcome in asphyxiated cooled infants. A combined brain amplitude integrated electroencephalography and near infrared spectroscopy study

    Brain Dev

    (2011)
  • K. Aso et al.

    Neonatal electroencephalography and neuropathology

    J Clin Neurophysiol

    (1989)
  • D. Azzopardi et al.

    Pilot study of treatment with whole body hypothermia for neonatal encephalopathy

    Pediatrics

    (2000)
  • N. Bayley

    Bayley scales of infant development: manual

    (1993)
  • E. Biagioni et al.

    Combined use of electroencephalogram and magnetic resonance imaging in full-term neonates with acute encephalopathy

    Pediatrics

    (2001)
  • B. Boashash et al.

    Time–frequency processing of nonstationary signals: advanced TFD design to aid diagnosis with highlights from medical applications

    Signal Process Mag IEEE

    (2013)
  • G. Boylan et al.

    An international survey of EEG use in the neonatal intensive care unit

    Acta Paediatr

    (2010)
  • Collaboration RTC

    Review manager (RevMan) 5.0

    (2008)
  • A. Csekő et al.

    Accuracy of amplitude-integrated electroencephalography in the prediction of neurodevelopmental outcome in asphyxiated infants receiving hypothermia treatment

    Acta Paediatr

    (2013)
  • L.M. Douglass et al.

    Burst suppression electroencephalogram pattern in the newborn: predicting the outcome

    J Child Neurol

    (2002)
  • L.M. Dubowitz

    The neurological assessment of the preterm and full-term newborn infant

    (1999)
  • A.D. Edwards et al.

    Neurological outcomes at 18 months of age after moderate hypothermia for perinatal hypoxic ischaemic encephalopathy: synthesis and meta-analysis of trial data

    BMJ

    (2010)
  • P. Eken et al.

    Predictive value of early neuroimaging, pulsed Doppler and neurophysiology in full term infants with hypoxic–ischaemic encephalopathy

    Arch Dis Child Fetal Neonatal Ed

    (1995)
  • Cited by (71)

    • Risk Assessment and Neurodevelopmental Outcomes

      2023, Avery's Diseases of the Newborn
    • EEG Spectral Power: A Proposed Physiological Biomarker to Classify the Hypoxic-Ischemic Encephalopathy Severity in Real Time

      2021, Pediatric Neurology
      Citation Excerpt :

      Electroencephalographic (EEG) qualitative and quantitative metrics are established biomarkers associated with brain injury. For example, EEG background of burst suppression, low voltage, and flat trace have been shown to predict neurodevelopmental outcomes.14 However, an experienced neurophysiologist is needed for interpretation and the reported reading depends on the complexity of the tracing and the interpreter's experience.15

    • A digitized approach for amplitude-integrated electroencephalogram transformation towards a standardized procedure

      2021, Biomedical Signal Processing and Control
      Citation Excerpt :

      Electroencephalography (EEG), using the modified international 10–20 electrode placement system, is the gold standard for the diagnosis of neonatal seizures [5,27] and neonatal encephalopathy [2].

    View all citing articles on Scopus
    View full text