The impact of genetic polymorphisms on the development of intraventricular haemorrhage, periventricular leucomalacia and hydrocephalus in very-low-birth-weight-infants

Background: As polymorphisms of genes involved in hemostasis or innate immune response are proposed to have functional relevance, they might influence the development and severity of brain diseases including intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL) and hydrocephalus in very-low-birth-weight-(VLBW)-infants.

Methods: We performed a genetic association study including 1696 infants: 225 VLBW-infants with IVH and/or PVL assessed by cerebral ultrasound studies, 971 VLBW-infants without IVH or PVL and 500 healthy term born infants. The following polymorphisms were determined by polymerase-chain-reaction (PCR): Factor-V-Leiden, prothrombin-G20210A, factor-XIII Val34Leu, interleukin-6-G(-174)C, and lymphotoxin-alpha-A252G.

Results: No polymorphism was more frequent in VLBW-infants with abnormal ultrasound-studies. In a subgroup analysis, the homozygous lymphotoxin-alpha-A252G-polymorphism was more frequently found in VLBW-infants with hydrocephalus requiring VP-shunting (n=39; 25.6%) than in VLBW-infants without hydrozephalus (11.5%; p=0.007) and in healthy infants born at term (10.5%).

Discussion: Although previous reports on polymorphisms selected by our group have described associations with intracranial haemorrhage or infarction in adults or VLBW-infants, we detected no significant associations in a large cohort of VLBW-infants. The impact of genetic risk factors is minor with respect to known clinical risk factors such as birth weight and gestational age.