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Early Amplitude-Integrated Electroencephalography for Monitoring Neonates at High Risk for Brain Injury

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Early Amplitude-Integrated Electroencephalography for Monitoring Neonates at High Risk for Brain Injury J Pediatr (Rio J). 2017;93(5):460---466 www.jped.com.br ORIGINAL ARTICLE Early amplitude-integrated electroencephalography ଝ for monitoring neonates at high risk for brain injury a,∗ a a Gabriel Fernando Todeschi Variane , Maurício Magalhães , Renato Gasperine , b b Heitor Castelo Branco Rodrigues Alves , Thiago Luiz Pereira Donoso Scoppetta , a a Rodrigo de Jesus Gonc¸alves Figueredo , Francisco Paulo Martins Rodrigues , a a,c a Alexandre Netto , Marcelo Jenne Mimica , Clery Bernardi Gallacci a Faculdade de Ciências Médicas da Santa Casa de São Paulo, Departamento de Pediatria, São Paulo, SP, Brazil b Faculdade de Ciências Médicas da Santa Casa de São Paulo, Departamento de Radiologia, São Paulo, SP, Brazil c Faculdade de Ciências Médicas da Santa Casa de São Paulo, Departamento de Patologia, São Paulo, SP, Brazil Received 16 June 2016; accepted 18 November 2016 Available online 23 February 2017 KEYWORDS Abstract Newborn; Objective: This study aimed to correlate amplitude-integrated electroencephalography findings with early outcomes, measured by mortality and neuroimaging findings, in a prospective cohort Brain injury; Amplitude-integrated of infants at high risk for brain injury in this center in Brazil. EEG; Methods: This blinded prospective cohort study evaluated 23 preterm infants below 31 weeks of gestational age and 17 infants diagnosed with hypoxic-ischemic encephalopathy secondary Early outcome to perinatal asphyxia, with gestational age greater than 36 weeks, monitored with amplitude- integrated electroencephalography in a public tertiary center from February 2014 to January 2015. Background activity (classified as continuous, discontinuous high-voltage, discontinuous low-voltage, burst-suppression, continuous low-voltage, or flat trace), presence of sleep-wake cycling, and presence of seizures were evaluated. Cranial ultrasonography in preterm infants and cranial magnetic resonance imaging in infants with hypoxic-ischemic encephalopathy were performed. Results: In the preterm group, pathological trace or discontinuous low-voltage pattern (p = 0.03) and absence of sleep-wake cycling (p = 0.019) were associated with mortality and brain injury assessed by cranial ultrasonography. In patients with hypoxic-ischemic encephalopathy, seizure patterns on amplitude-integrated electroencephalography traces were associated with mortality or brain lesion in cranial magnetic resonance imaging (p = 0.005). ଝ Please cite this article as: Variane GF, Magalhães M, Gasperine R, Alves HC, Scoppetta TL, Figueredo RJ, et al. Early amplitude-integrated electroencephalography for monitoring neonates at high risk for brain injury. J Pediatr (Rio J). 2017;93:460---6. ∗ Corresponding author. E-mail: [email protected] (G.F. Variane). http://dx.doi.org/10.1016/j.jped.2016.12.003 0021-7557/© 2017 Published by Elsevier Editora Ltda. on behalf of Sociedade Brasileira de Pediatria. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Early aEEG for monitoring neonates at high risk 461 Conclusion: This study supports previous results and demonstrates the utility of amplitude- integrated electroencephalography for monitoring brain function and predicting early outcome in the studied groups of infants at high risk for brain injury. © 2017 Published by Elsevier Editora Ltda. on behalf of Sociedade Brasileira de Pediatria. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/ by-nc-nd/4.0/). PALAVRAS-CHAVE Eletroencefalograma de amplitude integrada precoce no monitoramento de neonatos Recém-nascido; com risco elevado de lesão cerebral Lesão cerebral; Resumo EEG de amplitude integrada; Objetivo: Este estudo visou correlacionar os achados do eletroencefalograma de amplitude integrada (aEEG) com resultados precoces, medidos por mortalidade e achados de neuroim- Resultado precoce agem, em uma coorte prospectiva de neonatos com risco elevado de lesão cerebral em nosso centro no Brasil. Métodos: O estudo prospectivo de coorte cego avaliou 23 neonatos prematuros abaixo de 31 semanas de idade gestacional (IG) e 17 neonatos diagnosticados com Encefalopatia Hipóxico- Isquêmica (EHI) secundária à asfixia perinatal, com IG superior a 36 semanas, monitorados com aEEG em um centro terciário público de fevereiro de 2014 a janeiro de 2015. Foram avaliadas a atividade de base (classificada como padrão contínuo, descontínuo de alta voltagem, descon- tínuo de baixa voltagem, supressão de explosão, contínuo de baixa voltagem ou trac¸o plano), a presenc¸a de ciclo do sono-vigília e a presenc¸a de convulsões. Foram feitas a ultrassonografia craniana em prematuros e a ressonância magnética (RM) craniana em neonatos com EHI. Resultados: No grupo de prematuros, o trac¸o patológico ou padrão descontínuo de baixa volt- agem (p = 0,03) e a ausência de ciclo do sono-vigília (p = 0,019) foram associados a mortalidade e lesão cerebral avaliada por ultrassonografia craniana. Em pacientes com EHI, os padrões de con- vulsão nos trac¸ados do aEEG foram associados a mortalidade ou lesão cerebral na RM craniana (p = 0,005). Conclusão: Este estudo corrobora os resultados anteriores e demonstra a utilidade do aEEG no monitoramento da func¸ão cerebral e na predic¸ão de alterac¸ões precoces nos grupos de neonatos estudados com risco elevado de lesão cerebral. © 2017 Publicado por Elsevier Editora Ltda. em nome de Sociedade Brasileira de Pediatria. Este e´ um artigo Open Access sob uma licenc¸a CC BY-NC-ND (http://creativecommons.org/licenses/ by-nc-nd/4.0/). Introduction showed good predictive value of short- and long-term neuro- 11---13 logical prognosis. Other studies have shown that severe electroencephalographic abnormalities in preterm neonates The incidence of neurodevelopmental impairment in evaluated during the first 72 h of life are related to neurode- extremely preterm infants and those with hypoxic-ischemic 14,15 velopmental impairment. encephalopathy (HIE) secondary to perinatal asphyxia Given the severity of brain injury, as well its high mor- remains high in spite of advances in perinatal care. Stud- bidity and mortality rate, the identification of prognostic ies have estimated a global incidence of 345,000 premature factors with appropriate timing to provide early future infants and 233,000 infants with HIE per year with moder- 1,2 interventions is relevant. Therefore, this study aimed to ate/severe neurological impairment. Both populations are correlate aEEG findings with early outcomes, measured by considered at high risk for brain injury. mortality and neuroimaging findings, in a prospective cohort Different imaging methods can evaluate brain injury and 3 --- 5 of infants at high risk for brain injury in this center in Brazil. assess neurological prognosis. Acute electroencephalo- graphic abnormalities result from neuronal disorganization 6,7 and correlate with cognitive impairment. Amplitude- Methods integrated electroencephalography (aEEG) provides a clin- ically accessible method for continuous observation of This study was performed in a public tertiary center in cerebral background activity in ill infants at the bedside. Brazil. All infants born between February 2014 and January Thus, the utility of early aEEG for the assessment of the 2015, with gestational age (GA) above 36 weeks with HIE severity of cerebral injury and adverse outcomes in prema- secondary to perinatal asphyxia or with GA below 31 weeks, ture infants has been investigated as a tool for assessing were prospectively included in the study after parental con- 8---10 initial neonatal risk. sent was obtained. All subjects included were inborn. The The aEEG pattern is well correlated with conventional study was approved by the institutional ethics committee. EEG, and results in term newborns with perinatal asphyxia Infants with genetic syndromes or congenital malformations 462 Variane GF et al. incompatible with life were excluded, as these conditions To characterize background activity, 4-h periods of ade- could affect the results. quate monitoring were evaluated daily on days 1, 2, and The criteria for perinatal hypoxic-ischemic events 3 of life. Both aEEG readers were blinded to the clinical included the presence of at least two of the following: history. Cranial ultrasound (cUS) was performed at least (a) Apgar score below 5 at 5 min; (b) need for ventilation once a week in the neonatal period and cranial magnetic up to 10 min of life (intubation or ventilation under con- resonance imaging (MRI) was performed in all infants with tinuous positive airway pressure); (c) gas analysis of cord HIE between days four and ten of life. Clinical and imaging − blood in the first hour of life with pH < 7.10 or BE > 12. data were collected including with pre-established interest 16 The modified clinical Sarnat score was used to grade HIE. variables, such as demographic (sex, maternal age, race), The aEEG was recorded for 72 h as a two-channel EEG clinical (birth weight, gestational age, Apgar scores, diagno- from biparietal surface disk electrodes using an EEG device sis of early-onset sepsis, presence of clinical seizure, need (Neuron-Spectrum-4 and 5 systems with Neurospectrum for ventilatory support, surfactants, and vasoactive drugs), software module for aEEG and trending --- Neurosoft, Russia). and imaging data. The MRI examinations were assessed by Newborns with HIE who were treated with the institutional two independent neuroradiologists without knowledge of hypothermia protocol were evaluated for an additional
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