Mortality After Pediatric Arterial Ischemic Stroke
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Lauren A. Beslow, MD, MSCE, a Michael M. Dowling, MD, PhD, b Sahar M.A. Hassanein, MBBS, PhD,c John K. Lynch, DO, d MortalityDimitrios Zafeiriou, MD, PhD, e LisaAfter R. Sun, MD, f Ilona Pediatric Kopyta, PhD, g Luigi Titomanlio, MD, h Anneli Kolk, MD, i Anthony Chan, MBBS, j Jose Biller, MD, k Eric F. Grabowski, MD, ScD, l Abdalla A. Abdalla, MD, m Mark T. Mackay, ArterialMBBS, PhD, n Gabrielle deVeber, Ischemic MD, MSc, o on behalf of theStroke International Pediatric Stroke Study Investigators OBJECTIVES: abstract Cerebrovascular disease is among the top 10 causes of death in US children, but risk factors for mortality are poorly understood. Within an international registry, we METHODS: identify predictors of– in-hospital mortality after pediatric– arterial ischemic stroke (AIS). Neonates (0 28 days) and children (29 days <19 years) with AIS were enrolled from January 2003 to July 2014 in a multinational stroke registry. Death during hospitalization and cause of death were ascertained from medical records. Logistic RESULTS: regression was used to analyze associations between risk factors and in-hospital mortality. Fourteen of 915 neonates (1.5%) and 70 of 2273 children (3.1%) died during hospitalization. Of 48 cases with reported causes of death, 31 (64.6%) were stroke- – related, with remaining deaths attributed to medical disease. In multivariable analysis, P – P congenital heart disease (odds ratio [OR]: 3.88; 95% confidence interval [CI]: 1.23 12.29; – P = .021), posterior plus anterior circulation stroke (OR: 5.36; 95% CI: 1.70 16.85; = .004), and stroke presentation without seizures (OR: 3.95; 95% CI: 1.26 12.37; = .019) were – P – P associated with in-hospital mortality for neonates. Hispanic ethnicity (OR: 3.12; 95% CI: – P 1.56 6.24; = .001), congenital heart disease (OR: 3.14; 95% CI: 1.75 5.61; < .001), and posterior plus anterior circulation stroke (OR: 2.71; 95% CI: 1.40 5.25; = .003) were CONCLUSIONS: associated with in-hospital mortality for children. In-hospital mortality occurred in 2.6% of pediatric AIS cases. Most deaths were attributable to stroke. Risk factors for in-hospital mortality included congenital heart disease and posterior plus anterior circulation stroke. Presentation without seizures and Hispanic ethnicity were also associated with mortality for neonates and children, respectively. Awareness and study of risk factors for mortality represent opportunities to increase survival. WHAT’S KNOWN ON THIS SUBJECT: Stroke is among the top 10 causes of death among children according a Division of Neurology, Children’s Hospital of Philadelphia, and Departments of Neurology and Pediatrics, to administrative data in the United States, with Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; bDepartments of Pediatrics and Neurology, University of Texas Southwestern Medical Center, Dallas, Texas; cDepartment of differences in mortality possibly associated with Pediatrics, Ain Shams University, Cairo, Egypt; dSection on Stroke Diagnostics and Therapeutics, National geographic location, sex, and race. Institute of Neurologic Disorders and Stroke, National Institutes of Health, Bethesda, Maryland; eDivision of Child Neurology and Developmental Pediatrics, Aristotle University of Thessaloniki, Thessaloniki, Greece; fDepartment WHAT THIS STUDY ADDS: In this study, we add to our of Neurology, Johns Hopkins School of Medicine, Johns Hopkins University, Baltimore, Maryland; gDepartment of understanding of mortality rates among neonates Pediatric Neurology, School of Medicine, Medical University of Silesia, Katowice, Poland; hPediatric Emergency and children with arterial ischemic stroke and i Département, Hôpital Robert Debré, Paris, France; Department of Neuropsychology, University of Tartu, Tartu, identify both demographic and stroke-related risk Estonia; jDepartment of Pediatrics, McMaster Children’s Hospital, McMaster University, Hamilton, Canada; kDepartment of Neurology, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois; lDepartment factors for in-hospital mortality. of Pediatrics, Massachusetts General Hospital, Boston, Massachusetts; mDepartment of Neurosciences, Al Jalila Children’s Hospital, Dubai, United Arab Emirates; nDepartment of Neurology, The Royal Children’s Hospital, Melbourne, Australia; and oDivision of Neurology, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Canada To cite: Beslow LA, Dowling MM, Hassanein SMA, et al. Mortality After Pediatric Arterial Ischemic Stroke. Pediatrics. 2018;141(5):e20174146 Downloaded from www.aappublications.org/news by guest on September 25, 2021 PEDIATRICS Volume 141, number 5, May 2018:e20174146 ARTICLE ∼ 8 Childhood arterial ischemic mortality. We explored potential oxygenation, or other). Information stroke (AIS) affects 1.2– to 2.4 risk factors for mortality in a large regarding withdrawal of care per 100000 children1 per3 year in multinational cohort of children and included whether withdrawal was developed countries. In one study, neonates with AIS. entirely or in part due to stroke researchers used death certificates METHODS deficit severity or to an underlying from children in the United medical illness. Cause of death was States between 1979 and 1998 to Subjects and Study Design then classified as due to stroke, demonstrate a decline in mortality due to a combination of underlying due to all stroke subtypes4 during that medical disease and stroke, or due to period, including in AIS. This finding The International Pediatric Stroke underlying medical disease. Statistical Analysis was supported by the Global Burden Study (IPSS) is a multinational cohort of Disease Study, which revealed study of children aged 0 to <19 years a global trend toward a decrease with AIS or cerebral sinovenous in mortality among children with thrombosis. IPSS participation was Descriptive statistics included approved by the institutional review ischemic5 stroke between 1990 and counts and percentages for 2013. However, in 2015, childhood board of each contributing center. categorical variables, means cerebrovascular disease remained Informed consent and assent, when with SD for normally distributed among the top 10 causes of death appropriate, was obtained for each – continuous variables, and medians enrolled subject. This study is a among children6 in the United States with interquartile range (IQR) for (1 19 years), demonstrating retrospective analysis of the IPSS nonnormally distributed continuous that despite overall decreases registry and includes children >28 variables. A nonparametric test in mortality, stroke remains an days to <19 years and neonates 0 to of trend was used to determine important cause of pediatric deaths. 28 days of life diagnosed with AIS whether mortality changed during between January 1, 2003, and July the study period. Logistic regression Given differing stroke definitions 31, 2014. Subjects with concomitant was used to analyze associations and case ascertainment methods cerebral sinovenous thrombosis were between possible risk factors and among studies, risk factors for Dataexcluded. Abstraction odds of in-hospital mortality. The mortality remain poorly understood. following factors were hypothesized In the United States, Black race and “ ” to be associated with mortality: age living in certain geographic regions Enrolling institutions recorded at stroke, congenital heart disease, (southeastern stroke belt states) medical, laboratory, and imaging clinical stroke severity (Pediatric have been reported as mortality 4,7 data on a standardized IPSS data National Institutes of Health Stroke risk factors after childhood AIS. 9 collection form that included Scale [PedNIHSS] score), Black race, Geographic region was also demographics, clinical presentation, Hispanic ethnicity, and birth in a low- important in the Global Burden of stroke risk factors, imaging results, or middle- income (LAMI) country. Disease Study; an estimated 4043 laboratory data, treatment, and Only variables with <15% missing children aged 0 to 19 years died of outcome at discharge (normal, data were evaluated, with the ischemic stroke in 2013 globally (0.2 – death, neurologic deficit). Race and exception of the PedNIHSS because per 100000), with 3948 deaths in ethnicity were based on National it has previously been validated as developing countries (30 60-fold 10 Institutes of Health definitions a predictor of functional outcome. higher mortality than in developed 5 and assigned by the enrolling LAMI countries were defined by countries). 11 investigator. For those who died the World Bank. Subjects from 3 The Global Burden of Disease Study during hospitalization, centers were countries (Chile, Estonia, and Poland) also showed a trend toward higher recontacted to obtain date of death whose LAMI status changed to high mortality among male children5 with and cause of death. Causes of death income during the study period were ischemic stroke globally, a finding included those directly related to assigned LAMI status on the basis of not present in a previous4 report stroke (brain death, herniation, whether the birth country was LAMI from the United States. The authors hemorrhagic transformation, at the date of stroke ictus. Sites from “ ” of most reports on mortality after intracerebral hemorrhage, or other) the United States were categorized pediatric AIS have not examined or those related to an underlying as stroke belt states if located in specific stroke risk factors or stroke medical