Background and hypothesis Prolonged electroencephalographic (EEG) discontinuity has been associated with poor neurodevelopmental outcomes after perinatal asphyxia but its predictive value in the era of therapeutic hypothermia (TH) is unknown. In infants undergoing TH for hypoxic-ischaemic encephalopathy (HIE) prolonged EEG discontinuity is associated with cerebral tissue injury on MRI and adverse neurodevelopmental outcome.
Method Retrospective study of term neonates from three UK centres who received TH for perinatal asphyxia, had continuous two channel amplitude-integrated EEG with EEG for a minimum of 48 h, brain MRI within 6 weeks of birth and neurodevelopmental outcome data at a median age of 24 months. Mean discontinuity was calculated using a novel automated algorithm designed for analysis of the raw EEG signal.
Results Of 49 eligible infants, 17 (35%) had MR images predictive of death or severe neurodisability (unfavourable outcome) and 29 (59%) infants had electrographic seizures. In multivariable logistic regression, mean discontinuity at 24 h and 48 h (both p=0.01), and high seizure burden (p=0.05) were associated with severe cerebral tissue injury on MRI. A mean discontinuity >30 s/min-long epoch, had a specificity and positive predictive value of 100%, sensitivity of 71% and a negative predictive value of 88% for unfavourable neurodevelopmental outcome at a 10 µV threshold.
Conclusions In addition to seizure burden, excessive EEG discontinuity is associated with increased cerebral tissue injury on MRI and is predictive of abnormal neurodevelopmental outcome in infants treated with TH. The high positive predictive value of EEG discontinuity at 24 h may be valuable in selecting newborns with HIE for adjunctive treatments.
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Contributors JMD collected data, carried out the raw EEG data analysis, assisted with the statistical analysis, wrote the first draft of the manuscript and approved the final version of the manuscript. DW developed the EEG software used to measure discontinuity, assisted with writing the manuscript and approved of the final version of the manuscript. P Clarke obtained ethics approval, collected data, assisted with writing the manuscript and approved the final version of the manuscript. OK reviewed the MRIs and approved of the final version of the manuscript. P Chisholm carried out neurodevelopmental testing and approved the final version of the manuscript. JPB reviewed the MRIs, assisted with writing the first draft of the manuscript, assisted with statistical analysis and approved the final version of the manuscript. DKS conceived the study, collected data, assisted with the EEG reviews, statistical analysis, writing the first draft of the manuscript, approved of the final version of the manuscript and is guarantor.
Funding JPB received funding support from Theirworld.
Competing interests None declared.
Ethics approval UK REC reference 14/EE/0205.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement We have previously published one paper from this cohort relating seizure burden to brain injury in cooled babies and this is the remaining information.
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