title: Clinical Characteristics, Risk Factors, and Outcomes Associated With Neonatal Hemorrhagic Stroke: A Population-Based Case-Control Study.
abstract: Hemorrhage into the brain of term newborns often results in major injury and lifelong disability. The clinical epidemiology of neonatal hemorrhagic stroke (NHS) remains undefined, hindering the development of strategies to improve outcomes.
  
  
  
  To characterize the incidence, types, presentations, associated factors, and outcomes of neonatal hemorrhagic stroke.
  
  
  
  Population-based, nested case-control study. The Alberta Perinatal Stroke Project, a provincial registry, ascertained NHS cases using exhaustive diagnostic code searching (1992-2010, >2500 medical record reviews). Prospective cases were captured through the Calgary Pediatric Stroke Program (2007-2014). Participants included term neonates with magnetic resonance imaging-confirmed NHS including primary and secondary intracerebral hemorrhage, hemorrhagic transformation of ischemic injury, and presumed perinatal hemorrhagic stroke. Control infants with common data were recruited from a population-based study (4 to 1 ratio).
  
  
  
  Infants with NHS underwent structured medical record review using data-capture forms and blinded scoring of neuroimaging. Clinical risk factor common data elements were explored using logistic regression. Provincial live births were obtained from Statistics Canada. Outcomes were extrapolated to the Pediatric Stroke Outcome Measure.
  
  
  
  We identified 86 cases: 51 infants (59%) with NHS, of which 32 (67%) were idiopathic, 30 (35%) were hemorrhagic transformation of primary ischemic injuries (14 with neonatal cerebral sinovenous thrombosis, 11 with hypoxic ischemic encephalopathy, and 5 with neonatal arterial ischemic stroke), and 5 were presumed perinatal hemorrhagic stroke. Sixty-two percent were male. Incidence of pure NHS was 1 in 9500 live births and 1 in 6300 for all forms. Most presented in the first week of life with seizures and encephalopathy. Acute neurosurgical intervention was rare (3 of 86 total cases; 3.5%). Temporal lobe was the most common NHS location (16 of 51 pure NHS cases; 31%). A primary cause was evident in 19 of the 51 cases of non-hemorrhagic transformation NHS (37%). Idiopathic NHS was independently associated with lower maternal age (odds ratio [OR], 0.87; 95% CI, 0.78-0.94), primiparity (OR, 2.98; 95% CI, 1.18-7.50), prior spontaneous abortion (OR, 0.11; 95% CI, 0.02-0.53), difficult fetal transition (bradycardia [OR, 15.0; 95% CI, 2.19-101.9] and low Apgar [OR, 14.3; 95% CI, 2.77-73.5]), and small for gestational age (OR, 14.3; 95% CI, 1.62-126.1). Follow-up of 50 cases at a median of 37 months demonstrated poor neurological outcomes in 21 patients (44%).
  
  
  
  Neonatal hemorrhagic stroke is more common than previously reported, occurring in at least 1 in 6300 live births. Etiologies are approximately equally distributed between idiopathic, secondary, and hemorrhagic transformation. Clinical associations do not suggest a common mechanism or predictability of NHS. Recurrence is rare. Outcomes are often poor, mandating attention to prevention and rehabilitation.
authors.affiliation: Calgary Pediatric Stroke Program, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Lauran
authors.initials: L
authors.lastname: Cole
authors.affiliation: Department of Pediatrics, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Deborah
authors.initials: D
authors.lastname: Dewey
authors.affiliation: Department of Pediatrics, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Nicole
authors.initials: N
authors.lastname: Letourneau
authors.affiliation: Department of Pediatrics, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Bonnie J
authors.initials: BJ
authors.lastname: Kaplan
authors.affiliation: Department of Community Health Services, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Chaput
authors.affiliation: Department of Pediatrics, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Clare
authors.initials: C
authors.lastname: Gallagher
authors.affiliation: Calgary Pediatric Stroke Program, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Jacquie
authors.initials: J
authors.lastname: Hodge
authors.affiliation: Calgary Pediatric Stroke Program, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Amalia
authors.initials: A
authors.lastname: Floer
authors.affiliation: Calgary Pediatric Stroke Program, University of Calgary, Calgary, Alberta, Canada2Department of Pediatrics, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada3Department of Community Health Services, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada4Department of Clinical Neuroscience, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Adam
authors.initials: A
authors.lastname: Kirton
mesh_terms: D002170:Canada; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000453:epidemiology / Q000209:etiology; D020300:Intracranial Hemorrhages / Q000453:epidemiology / Q000209:etiology*; D008297:Male; D017063:Outcome Assessment, Health Care; D012042:Registries; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology / Q000209:etiology*