Epidemiology of Perinatal Stroke
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2021-06-18
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Abstract
Perinatal stroke is a collection of distinct clinicoradiographic syndromes resulting in injury to the developing brain between 20 weeks gestation and 28 days post-natal age. Perinatal stroke is the leading cause of hemiparetic cerebral palsy and also causes other adverse outcomes such as epilepsy and neurodevelopmental challenges, as well as significant economic burden and emotional burden for families. The birth prevalence was estimated to be between 1/1600 births and 1/3000 births depending on definitions and study methodology; however, no published study to date had evaluated all six subtypes of perinatal stroke birth prevalence to define their relative prevalence and other characteristics such as sex ratios and changes over time. Each subtype of perinatal stroke requires individual characterization of birth prevalence, risk factors and outcomes to better inform early diagnosis, treatment and prevention. Some subtypes of perinatal stroke such as neonatal arterial ischemic stroke have been well studied, while for others such as periventricular venous infarction (PVI), birth prevalence and risk factors remain unknown. In this thesis the birth prevalence of all six types of perinatal stroke was estimated using the Alberta Perinatal Stroke Project (APSP), a population-based registry of all types of perinatal stroke in Southern Alberta, Canada. We also compared retrospective methods using administrative data, and prospective methods using the APSP registry. Poisson regression was used to assess changes in annual birth prevalence over time. To further characterize PVI, a systematic review and individual patient data meta-analysis was conducted to consolidate data about antenatally-diagnosed germinal matrix intraventricular hemorrhage, which is believed to be the pathophysiology for PVI. Logistic regression was used to evaluate outcomes and co-occurring conditions. We found the highest estimated birth prevalence of perinatal stroke to date of 1/1100 births, which is a rate of one per day in Canada. In addition, novel insights were determined regarding the relative proportions and sex proportions of the stroke subtypes, including the finding that males with arterial ischemic stroke are more likely than females to present in the perinatal period. Periventricular venous infarction was found to be the second most common subtype of perinatal stroke, and systematic review and individual patient data meta-analysis demonstrated that the grading system developed for delivered preterm infants is relevant to fetuses and that outcome may be additionally influenced by gestational age at birth. In addition, a variety of co-occurring conditions were identified. This thesis presents an estimated birth prevalence of perinatal stroke that is higher than previously thought and posits that it must be calculated as a sum of the perinatal stroke subtypes. Our results set the stage for exciting new studies to better understand the role of sex in neonatal seizures as a presentation of brain injury, as well as established the groundwork for case-control studies of risk factors in periventricular venous infarction. Increased knowledge of epidemiology and understanding of risk factors is crucial to develop strategies for early diagnosis, treatment and ideally prevention of perinatal stroke.
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Dunbar, M. J. (2021). Epidemiology of Perinatal Stroke (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.