Epidemiology and pathogenesis of stroke in preterm infants: A systematic review

BACKGROUND: Perinatal stroke is one of the principal causes of cerebral palsy (CP) in preterm infants. Stroke in preterm infants is different from stroke in term infants, given the differences in brain maturation and the mechanisms of injury exclusive to the immature brain. We conducted a systematic review to explore the epidemiology and pathogenesis of periventricular hemorrhagic infarction (PVHI), perinatal arterial ischemic stroke (PAIS) and cerebral sinovenous thrombosis (CSVT) in preterm infants. METHODS: Studies were identified based on predefined study criteria from MEDLINE, EMBASE, SCOPUS and WEB OF SCIENCE electronic databases from 2000 –2019. Results were combined using descriptive statistics. RESULTS: Fourteen studies encompassed 546 stroke cases in preterm infants between 23 –36 weeks gestational ages and birth weights between 450 –3500 grams. Eighty percent (436/546) of the stroke cases were PVHI, 17%(93/546) were PAIS and 3%(17/546) were CSVT. Parietal PVHI was more common than temporal and frontal lobe PVHI. For PAIS, left middle cerebral artery (MCA) was more common than right MCA or cerebellar stroke. For CSVT partial or complete thrombosis in the transverse sinus was universal. All cases included multiple possible risk factors, but the data were discordant precluding aggregation within a meta-analysis. CONCLUSION: This systematic review confirms paucity of data regarding the etiology and the precise causal pathway of stroke in preterm infants. Moreover, the preterm infants unlike the term infants do not typically present with seizures. Hence high index of clinical suspicion and routine cUS will assist in the timely diagnosis and understanding of stroke in this population.