Prospective assessment of risk factors for recurrent stroke during childhood--a 5-year follow-up study

Lancet. 2002 Nov 16;360(9345):1540-5. doi: 10.1016/S0140-6736(02)11520-0.


Background: Risk factors for arterial stroke in children include congenital heart malformations, vasculopathies, infectious diseases, collagen tissue diseases, and metabolic disorders. Results of previous case-control studies have shown an association between ischaemic stroke and hereditary prothrombotic risk factors: factor V G1691A and factor II G20210A mutations, raised lipoprotein (a), and deficiencies in antithrombin, protein C, and protein S. The relevance of these factors to a second ischaemic stroke event is not known.

Methods: We assessed the risk of a second arterial ischaemic stroke associated with these prothrombotic risk factors, with underlying diseases or stroke comorbidities, and with stroke subtypes (cardiac, vascular, infectious, idiopathic). 167 boys and 134 girls aged between 6 months and 18 years of age (median 7 years) with a first episode of ischaemic stroke were followed-up prospectively for a median of 44 months (range 20-56).

Findings: Recurrent ischaemic stroke was diagnosed in 20 of 301 children who survived (6.6%) at a median of 5 months (range 1.5-36) after first stroke onset. The relative risk of having a second stroke was significantly increased in patients with raised lipoprotein (a) (relative risk 4.4, 95% CI 1.9-10.5) and in children with familial protein C deficiency (3.5, 1.1-10.9). Additionally, survival analysis showed that a first ischaemic stroke of vascular origin was significantly associated with having a second stroke (odds ratio 3.9, 95% CI 1.4-10.6).

Interpretation: Raised lipoprotein (a), protein C deficiency, and stroke of vascular origin are risk factors for recurrent arterial ischaemic stroke in childhood.

Publication types

  • Multicenter Study

MeSH terms

  • Adolescent
  • Blood Coagulation Disorders / complications*
  • Blood Coagulation Disorders / genetics
  • Calcium / physiology
  • Child
  • Child, Preschool
  • Female
  • Follow-Up Studies
  • Humans
  • Infant
  • Lipoprotein(a) / blood
  • Male
  • Mutation
  • Prospective Studies
  • Protein C Deficiency / complications
  • Protein S Deficiency / complications
  • Prothrombin / physiology
  • Recurrence
  • Risk Factors
  • Stroke / classification
  • Stroke / etiology*


  • Lipoprotein(a)
  • Prothrombin
  • Calcium