Stroke Impact of Thrombophilia on Risk of Arterial Ischemic Stroke or Cerebral Sinovenous Thrombosis in Neonates and Children A Systematic Review and Meta-Analysis of Observational Studies

Background—The aim of this study was to estimate the impact of thrombophilia on risk of first childhood stroke through a meta-analysis of published observational studies. Methods and Results—A systematic search of electronic databases (Medline via PubMed, EMBASE, OVID, Web of Science, The Cochrane Library) for studies published from 1970 to 2009 was conducted. Data on year of publication, study design, country of origin, number of patients/control subjects, ethnicity, stroke type (arterial ischemic stroke [AIS], cerebral venous sinus thrombosis [CSVT]) were abstracted. Publication bias indicator and heterogeneity across studies were evaluated, and summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated with fixed-effects or random-effects models. Twenty-two of 185 references met inclusion criteria. Thus, 1764 patients (arterial ischemic stroke [AIS], 1526; cerebral sinus venous thrombosis [CSVT], 238) and 2799 control subjects (neonate to 18 years of age) were enrolled. No significant heterogeneity was discerned across studies, and no publication bias was detected. A statistically significant association with first stroke was demonstrated for each thrombophilia trait evaluated, with no difference found between AIS and CSVT. Summary ORs (fixed-effects model) were as follows: Conclusions—The present meta-analysis indicates that thrombophilias serve as risk factors for incident stroke. However, the impact of thrombophilias on outcome and recurrence risk needs to be further investigated. Key Words: cerebrovascular disorders Ⅲ meta-analysis Ⅲ pediatrics Ⅲ thrombophilia T he incidence of stroke in neonates and children (arterial ischemic stroke [AIS] or cerebral sinus venous thrombosis [CSVT]) is estimated to be between 2.6 and 6.4 per 100 000 per year, reflecting a trend toward a higher frequency in more current literature. 1–3 Underlying conditions in children with symptomatic cerebrovascular accidents include congenital heart malformations, hemolytic anemias, and col-lagen vascular diseases, as well as some rare inborn metabolic disorders. 4 In addition, risk factors include trauma and infectious diseases. Apart from acquired thrombophilic risk factors such as the presence of antiphospholipid antibodies, 5,6 inherited thrombophilia, particularly antithrombin, protein C, and protein S deficiency, variants of coagulation factor V (G1691A) and factor II (G20210A), and elevated lipopro-tein(a), have been found in small case series and case-control studies to be associated with AIS or CSVT in infants and children. 7–52 Furthermore, an association of the thermolabile MTHFR C677T genotype with stroke is controversial in both adults and children. 5353 In fact, the increased likelihood of having a blood clot in the vasculature is related to elevated homocysteine levels, and mutations in …