Increased risk of intraventricular hemorrhage in preterm infants with thrombophilia

Abstract

The multifactorial etiology of cerebral intraventricular hemorrhage (IVH) may involve coagulation disturbances and venous infarction. We tested whether coagulation abnormalities associated with adult venous thrombosis would constitute a risk factor for IVH in newborn infants. In 22 infants (gestational age 24.3-39.9 wk, median 28.0 wk) with neonatal IVH grade II to IV, the frequencies of congenital resistance to activated protein C due to a point mutation in the factor V gene (Gln506-FV) and a polymorphism in the prothrombin gene (G20210A-FII) were assessed and compared with those observed in 29 premature newborn infants without IVH and in 302 (Gln506-FV) or 526 (G20210A-FII) healthy adults. In infants with IVH, four (18%) heterozygous carriers of Gln506-FV and one (5%) heterozygous carrier of G20210A-FII were found. One infant without IVH was heterozygous for Gln506-FV (3%). When compared with the frequency of Gln506-FV in the general population, the odds ratio for being a carrier of Gln506-FV for patients with IVH was 5.9 (95% confidence interval 1.7-20.3, p = 0.013) and for patients without IVH 0.9 (95% confidence interval 0.1-7.6, p > 0.99). The absolute risk of IVH in a newborn infant with heterozygous Gln506-FV and born before 30 wk of gestation was estimated at 80%, whereas the corresponding risk for all infants born before 30 wk was 14%. Gln506-FV was more common in newborn infants with IVH than in the general population, whereas there was no difference in the frequencies of Gln506-FV in infants without IVH and in the general population. Thus, Gln506-FV may be a risk factor of IVH. The risk of IVH in a premature infant with Gln506-FV or other established thrombophilic coagulation abnormality may be considerable.