the Childhood Stroke Study GroupBackground-The present study was performed to assess the association of prothrombotic risk factors and underlying conditions (infections, vascular trauma, immobilization, malignancies, autoimmune diseases, renal diseases, metabolic disorders, obesity, birth asphyxia, cardiac malformations, and use of prothrombotic drugs) with cerebral venous thrombosis (CVT) in children. Methods and Results-From 1995 to 2002, 149 pediatric patients aged newborn to Ͻ18 years (median 6 years) with CVT were consecutively enrolled. In patients and in 149 age-and gender-matched children with similar underlying clinical conditions but without CVT, the factor V G1691A mutation, the factor II G20210A variant, lipoprotein(a) [Lp(a)], protein C, protein S, antithrombin, and antiphospholipid antibodies, as well as associated clinical conditions, were investigated. Eighty-four (56.4%) of the patients had at least 1 prothrombotic risk factor compared with 31 control children (20.8%; PϽ0.0001). In addition, 105 (70.5%) of 149 patients with CVT presented with an underlying predisposing condition. On univariate analysis, factor V, protein C, protein S, and elevated Lp(a) were found to be significantly associated with CVT. However, in multivariate analysis, only the combination of a prothrombotic risk factor with an underlying condition (OR 3.9, 95% CI 1.8 to 8.6), increased Lp(a) (OR 4.1, 95% CI 2.0 to 8.7), and protein C deficiency (OR 11.1, 95% CI 1.2 to 104.4) had independent associations with CVT in the children investigated. Conclusions-CVT in children is

for the Childhood Stroke Study GroupBackground and Purpose-The present study was performed to evaluate the rate of recurrent symptomatic thromboembolism with respect to prothrombotic risk factors and underlying clinical conditions. Methods-In a series of 215 consecutively enrolled neonates with arterial ischemic stroke (AIS), the factor V G1691A mutation, factor II G20210A variant, methylenetetrahydrofolate reductase (MTHFR) T677T genotype, lipoprotein (Lp) (a), antithrombin, protein C, protein S, and anticardiolipin antibodies (ACA) were investigated. Patient median follow-up was 3.5 years (range, 1 to 8 years). Results-During follow-up, 7 infants and children (3.3%) showed recurrent symptomatic thromboembolism (AIS, nϭ4; venous sinus thrombosis, nϭ2; deep vein thrombosis of the leg, nϭ1). The factor V mutation, factor II variant, elevated Lp(a) Ͼ30 mg/dL, protein C deficiency, and protein S or antithrombin deficiency were associated with first stroke onset.

With the present study we can show for the first time that the embryonal MTHFR 677TT genotype is significantly associated with the development of structural congenital heart malformations during early pregnancy. It remains to be clarified, whether this genotype is at least a risk marker or a risk factor for structural congenital heart malformations.