LACK OF ASSOCIATION OF THROMBOPHILIC POLYMORPHISMS WITH PERINATAL STROKE: A CASE CONTROL STUDY

Objectives: Many case series have documented prothrombotic abnormalities in children with presumed perinatal stroke. These studies, however, have not included controls. We set out to document the association between genetic polymorphisms for thrombophilia and perinatal stroke using a case-control methodology.

Methods: This was a case-control study. Cases included twenty-four children with radiologically proven presumed perinatal ischemic stroke. Controls included forty-six Neonatal ICU patients of the same institution. We evaluated subjects for the presence of four genetic mutations: Factor V Leiden, Prothrombin 20210 mutation, and both MTHFR (677 and 1298) mutations.

Results: The four mutations studied were found equally commonly among cases and controls (75% (18/24) vs. 72% (33/46)). Differences in numbers of cases and controls with the Factor V Leiden Mutation (4/24 vs. 3/46) and Prothrombin Gene Mutation (1/24 vs. 0/46) were not statistically significant. The MTHFR C677T mutation was common in both populations, with heterozygotes comprising 7/22 of the perinatal stroke group and 19/46 of the control group (NS). Homozygotes comprised 3/22 of the cases vs. 3/46 of controls. The MTHFR A1298C mutation was common in both groups (50% (8/16) vs. 56% (14/25)).

Conclusion: As others have shown, many children with perinatal stroke in this series carry thrombophilic polymorphisms. These polymorphisms, however, were found to occur equally frequently in our cases and controls. This calls into question the direct link between prothrombotic abnormalities in the neonate and perinatal stroke, suggesting that other factors may play an important role in perinatal stroke. Further studies evaluating the relationships between vascular events of the CNS in the perinatal period, maternal and fetal thrombophilia, and pregnancy complications are warranted.