The role of genes of renin-angiotensin system in the development of adverse outcomes of treatment in severe intraventricular hemorrhages in premature infants

Introduction: Intraventricular hemorrhage (IVH) causes increased morbidity and mortality in premature infants and is associated with adverse neurological outcomes. The aim of the research is to confirm the role of genes of renin-angiotensin system in the development of adverse outcomes of treatment of severe IVC in preterm. Materials and methods: A prospective study was conducted, which included 58 premature infants (average birth weight 1016.8 ± 52.59 g, gestational age 26.96 ±0.33 weeks), who were treated at medical institutions in Poltava region during 2012-2015. I/D polymorphism of ACE gene, A/C polymorphism of AGT2R1 gene and 4a/b polymorphism of the eNOS gene were studied. The distribution of the genotype was compared between groups using the χ2 analysis. Results: Out of 58 children enrolled in the study, 33 (56.9%) of infants developed ventricular dilatation, which in 8 (13.8%) of the newborns progressed to hydrocephalus. Thirty-four (58.6%) infants with severe IVHs died. The average (median) time of death of infants was 10.6 days. Among children who died, a combination of genotypes ID & DD of the gene ACE +4ab & 4AA of the eNOS gene was found significantly more often than in children who survived, and at the border of statistical significance - the isolated genotype 4ab & 4 aa of the eNOS gene. The combination of genotype ID+DD of the ACE gene and the AC + CC genotype of the AGTR1 gene was significantly more frequent among children with ventricular dilatation than in children without it. The weight at birth have negative correlation trends with lethal outcomes and do not have with ventricular dilatation and hydrocephalus. Conclusions: Lethal outcomes in children with IVH are associated with weight at birth, as well as the presence of a combination of genotypes ID+DD of the ACE gene and 4ab+4aa of the eNOS gene.