Elsevier

The Journal of Pediatrics

Volume 187, August 2017, Pages 34-42
The Journal of Pediatrics

Original Articles
Amplitude-Integrated Electroencephalography Improves the Identification of Infants with Encephalopathy for Therapeutic Hypothermia and Predicts Neurodevelopmental Outcomes at 2 Years of Age

https://doi.org/10.1016/j.jpeds.2017.04.041Get rights and content

Objectives

To examine whether using an amplitude-integrated electroencephalography (aEEG) severity pattern as an entry criterion for therapeutic hypothermia better selects infants with hypoxic-ischemic encephalopathy and to assess the time-to-normal trace for aEEG and magnetic resonance imaging (MRI) lesion load as 24-month outcome predictors.

Study design

Forty-seven infants meeting Norwegian therapeutic hypothermia guidelines were enrolled prospectively. Eight-channel EEG/aEEG was recorded from 6 hours until after rewarming, and read after discharge. Neonatal MRI brain scans were scored for summated (range 0-11) regional lesion load. A poor outcome at 2 years was defined as death or a Bayley Scales of Infant-Toddler Development cognitive or motor composite score of <85 or severe hearing or visual loss.

Results

Three severity groups were defined from the initial aEEG; continuous normal voltage (CNV; n = 15), discontinuous normal voltage (DNV; n = 18), and a severe aEEG voltage pattern (SEVP; n = 14). Any seizure occurrence was 7% CNV, 50% DNV, and 100% SEVP. Infants with SEVP with poor vs good outcome had a significantly longer median (IQR) time-to-normal trace: 58 hours (9-79) vs 18 hours (12-19) and higher MRI lesion load: 10 (3-10) vs 2 (1-5). A poor outcome was noted in 3 of 15 infants with CNV, 4 of 18 infants with DNV, and 8 of 14 infants with SEVP. Using multiple stepwise linear regression analyses including only infants with abnormal aEEG (DNV and SEVP), MRI lesion load significantly predicted cognitive and motor scores. For the SEVP group alone, time-to-normal trace was a stronger outcome predictor than MRI score. No variable predicted outcome in infants with CNV.

Conclusions

Selection of infants with encephalopathy for therapeutic hypothermia after perinatal asphyxia may be improved by including only infants with an early moderate or severely depressed background aEEG trace.

Section snippets

Methods

Full-term newborn infants with perinatal asphyxia treated with therapeutic hypothermia were enrolled prospectively from a single center (Ullevål Neonatal Intensive Care Unit, Oslo University Hospital, Oslo, Norway) from January 1, 2010 to December 31, 2011. Fifty-three neonates were treated with whole body cooling for 3 days as standard of care under the Norwegian National Guidelines for therapeutic hypothermia.11 In 3 infants, consent to partake in the study was not obtained, and 3 others were

Results

Table I shows the demographic, baseline, clinical, and outcome variables for the 47 included infants, divided into 3 severity groups based on their initial aEEG pattern. Fifteen infants had CNV (normal), 18 had DNV (moderately abnormal), and 14 had SEVP (severely abnormal) aEEG patterns.17, 18 The median start time of aEEG monitoring for the whole cohort was 6 hours. The aEEG was applied earlier in the CNV (median 4 hours) than the DNV (7 hours) and SEVP (6 hours) groups, because more CNV were

Discussion

The first 3 large, randomized, controlled trials of therapeutic hypothermia5, 8, 10 included infants with moderate or severe, but not mild, encephalopathy. These trials used similar entry criteria except that the presence of a depressed aEEG as a marker of encephalopathy was not used in the National Institute of Child Health and Development trial as an entry criterion. Presently, centers outside the United States, particularly those who initiate therapeutic hypothermia without recording an

References (39)

  • J.M. Perlman et al.

    Part 11: neonatal resuscitation: 2010 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science with Treatment Recommendations

    Circulation

    (2010)
  • M.A. Tagin et al.

    Hypothermia for neonatal hypoxic ischemic encephalopathy: an updated systematic review and meta-analysis

    Arch Pediatr Adolesc Med

    (2012)
  • D. Azzopardi et al.

    The TOBY Study. Whole body hypothermia for the treatment of perinatal asphyxial encephalopathy: a randomized controlled trial

    BMC Pediatr

    (2008)
  • D.V. Azzopardi et al.

    Moderate hypothermia to treat perinatal asphyxial encephalopathy

    N Engl J Med

    (2009)
  • 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)
  • S.E. Jacobs et al.

    Cooling for newborns with hypoxic ischaemic encephalopathy

    Cochrane Database Syst Rev

    (2013)
  • S. Shankaran et al.

    Whole- body hypothermia for neonates with hypoxic-ischemic encephalopathy

    N Engl J Med

    (2005)
  • G. Simbruner et al.

    Systemic hypothermia after neonatal encephalopathy: outcomes of neo.nEURO.network RCT

    Pediatrics

    (2010)
  • J.H. Skranes et al.

    Keeping a cool head

    Paidos

    (2011)
  • Cited by (45)

    • MRI combined with early clinical variables are excellent outcome predictors for newborn infants undergoing therapeutic hypothermia after perinatal asphyxia

      2021, EClinicalMedicine
      Citation Excerpt :

      These are the severity pattern of aEEG, [21,24] the peak LDH (LDHpeak), LDH value at 72h (LDH72h), [25,26] time for plasma lactate to fall below 5 mmol (lactatehrs<5mmol) [21] and the number of inotropic and anticonvulsant drugs used during TH [27] as proxy-markers for hypotension and seizure burden respectively. We confirm in this paper the usefulness of these measures previously proposed for outcome prediction [21,24,26,27]. In this population-based cohort study with a wide range of infants, with HIE including those with comorbidities or additional diagnoses more representative of current cooling practices we aim to test:

    View all citing articles on Scopus

    J.S. has a PhD fellowship from the Faculty of Medicine, University of Oslo. M.T. is funded by the University of Oslo, The Norwegian Research Council and SPARKS (UK) Charitable foundation. The authors declare no conflicts of interest.

    View full text