Amplitude Integrated Electroencephalogram as a Prognostic Tool in Neonates with Hypoxic-Ischemic Encephalopathy: A Systematic Review

PLoS One. 2016 Nov 1;11(11):e0165744. doi: 10.1371/journal.pone.0165744. eCollection 2016.


Introduction: Perinatal management and prognostic value of clinical evaluation and diagnostic tools have changed with the generalization of therapeutic hypothermia (TH) in infants with hypoxic-ischemic encephalopathy (HIE).

Aim: to ascertain the prognostic value of amplitude integrated electroencephalogram (aEEG) in neonates with HIE considering hours of life and treatment with TH.

Methods: A systematic review was performed. Inclusion criteria were studies including data of neonates with HIE, treated or not with TH, monitored with aEEG and with neurodevelopmental follow-up of at least 12 months. The period of bibliographic search was until February 2016. No language restrictions were initially applied. Consulted databases were MEDLINE, Scopus, CINHAL and the Spanish language databases GuiaSalud and Bravo. Article selection was performed by two independent reviewers. Quality for each individual paper selected was evaluated using QUADAS-2. Review Manager (RevMan) version 5.3 software was used. Forest plots were constructed to graphically show sensitivity and specificity for all included studies, separating patients treated or not with hypothermia. Summary statistics were estimated using bivariate models and random effects approaches with the R package MADA from summary ROC curves. Meta-regression was used to estimate heterogeneity and trends.

Results: from the 403 articles initially identified, 17 were finally included and critically reviewed. In infants not treated with hypothermia the maximum reliability of an abnormal aEEG background to predict death or moderate/severe disability was at 36 hours of life, when a positive post-test probability of 97.90% was achieved (95%CI 88.40 to 99.40%). Positive likelihood ratio (+LR) at these hours of life was 26.60 (95%CI 4.40 to 94.90) and negative likelihood ratio (-LR) was 0.23 (95%CI 0.10 to 0.44). A high predictive value was already present at 6 hours of life in this group of patients, with a positive post-test probability of 88.20% (95%CI 79.80 to 93%) and a +LR of 4.34 (95%CI 2.31 to 7.73). In patients treated with TH the maximum predictive reliability was achieved at 72 hours of life (post-test probability of 95.70%, 95%CI 84.40 to 98.50%). +LR at this age was 24.30 (95%CI 5.89 to 71.30) and-LR was 0.40 (95%CI 0.25 to 0.57). Predictive value of aEEG at 6 hours of life was low in these patients (59.10%, 95%CI 55.70 to 63%).

Conclusion: This study confirms that aEEG´s background activity, as recorded during the first 72 hours after birth, has a strong predictive value in infants with HIE treated or not with TH. Predictive values of traces throughout the following 72 hours are a helpful guide when considering and counselling parents about the foreseeable long-term neurological outcome.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Brain Diseases / complications*
  • Brain Diseases / diagnosis*
  • Electroencephalography / methods*
  • Humans
  • Hypoxia-Ischemia, Brain / complications*
  • Infant, Newborn
  • Prognosis

Grants and funding

This review was part of the Spanish National Health System Clinical Practice Guideline (CPG) on HIE. Funding was received for the development of the whole CPG from the Agencia de Qualitat i Avaluació Sanitàries de Catalunya (public quality agency linked to the Health Department of the Catalan Government).