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Original Investigation
March 2017

Clinical Characteristics, Risk Factors, and Outcomes Associated With Neonatal Hemorrhagic StrokeA Population-Based Case-Control Study

Author Affiliations
  • 1Calgary Pediatric Stroke Program, University of Calgary, Calgary, Alberta, Canada
  • 2Department of Pediatrics, Alberta Children’s Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada
  • 3Department of Community Health Services, Alberta Children’s Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada
  • 4Department of Clinical Neuroscience, Alberta Children’s Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada
JAMA Pediatr. 2017;171(3):230-238. doi:10.1001/jamapediatrics.2016.4151
Key Points

Question  What are the incidence, types, presentations, associated factors, and long-term outcomes of neonatal hemorrhagic stroke?

Findings  This population-based case-control study found a neonatal hemorrhagic stroke incidence of 1 in 6300 live births and independent associations between idiopathic neonatal hemorrhagic stroke and lower maternal age, primiparity, prior spontaneous abortion, difficult fetal transition, and small for gestational age. Outcomes were poor in approximately 50% of infants including sensorimotor delays and epilepsy.

Meaning  Neonatal hemorrhagic stroke is more common than previously reported, and clinical risk factors associated with idiopathic neonatal hemorrhagic stroke do not support a primary acquired pathophysiology.

Abstract

Importance  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.

Objective  To characterize the incidence, types, presentations, associated factors, and outcomes of neonatal hemorrhagic stroke.

Design, Setting, and Participants  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).

Main Outcomes and Measures  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.

Results  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%).

Conclusions and Relevance  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.

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