The effect of the Val34Leu polymorphism in the factor XIII gene in infants with a birth weight below 1500 g

OBJECTIVES: The 34Leu polymorphism of the factor XIII gene is associated with a low rate of brain infarction and a higher incidence of primary intracerebral hemorrhage in adults. We evaluated the effect of the polymorphism on the subsequent development of isolated intracranial hemorrhage and white matter disease in preterm infants with a birth weight <1500 g (very low birth weight VLBW] infants). STUDY DESIGN: We studied 531 VLBW infants and 301 control infants born at term. The factor XIII 34Leu polymorphism was detected by polymerase chain reaction and restriction enzyme digestion. RESULTS: Allele frequencies were not different from term and VLBW infants (Val/Val, 53.1% and 57.8%; Val/Leu, 38.8% and 37.6%; Leu/Leu, 8.0% and 4.5%, respectively). VLBW infants carrying the Leu/Val or Leu/Leu allele had a significant reduced risk of the development of white matter disease (3.6% vs 10.4% in infants without the polymorphism, P =.003). In a multivariate logistic regression analysis, only gestational age <28 weeks (odds ratio, 3.8; 95% confidence interval, 1.9-7.5; P <.001), and the factor XIII 34Leu allele (odds ratio, 0.3; 95% confidence interval, 0.1-0.7; P =.005) had significant prognostic value in predicting subsequent white matter disease. However, VLBW infants who carried the factor XIII 34Leu allele also had a moderately increased risk of the subsequent development of isolated intraventricular hemorrhage (14.3% vs 10.1% in infants without the mutation, P =.17). CONCLUSIONS: VLBW infants carrying the factor XIII 34Leu polymorphism had a decreased risk for white matter disorders.