Predictors of CNS injury in neonates with hypoxic-ischemic encephalopathy

Abstract

Introduction. According to WHO, the main neurological causes of disability and mortality in newborns remain asphyxia and hypoxic-ischemic encephalopathy (HIE). Oxidative stress results from an imbalance between the production of reactive oxygen species and the ability of the body’s antioxidant system to neutralize them. Increased production of reactive oxygen species may be caused by an inflammatory response and hypoxia, leading to damage to lipids, proteins, and cellular DNA. Indicators of nitrate metabolism, according to literature data, are markers for early diagnosis of hypoxic-ischemic CNS damage in premature infants. IL-1β gene polymorphism is associated with an increased risk of IVH and periventricular leukomalacia. Aim. To investigate the features of metabolism (in terms of nitrates, nitrites, malone-D-aldehyde (MDA) and sialic acids) in infants aged 6-9 months who were born from mothers with metabolic syndrome and who had HIE in the early neonatal period, as well as to establish associations between the genotypes of the eNOS (G894T), IL1B (C3953T) genes and the abovementioned metabolites. Materials and methods. Prospective case-control study involved 40 newborns, main group (n=16) diagnosed with “Hypoxic-ischemic encephalopathy of the newborn” (P91.6 according to ICD-10) aged 6-9 months, comparison group – conditionally healthy full-term children (n=14) aged 6-9 months. Determination of nitrate, nitrite, MDA, and sialic acid concentrations was performed by spectrophotometric method in the urine of children in the study groups. Determination of polymorphic variants of eNOS and IL1B was carried out by polymerase chain reaction. Results. The study of nitric oxide metabolism in the groups of examined children showed that in the infants of the main group during the period of 6-9 months of life, the concentration of nitrites was significantly higher than in the children of the comparison group (2.69 nmol/l versus 1.39 nmol/l, p<0.001), similar differences were obtained in the concentration of nitrates (p<0.001). It should be noted that a significant direct relationship was found between MDA and sialic acids in multiple Poisson regression analysis after correction for the gestational age of the child (Coef. 1.27 (95% CI 0.25- 0.29; p=0.014). We did not find significant differences in the levels of nitrates, nitrites, sialic acids and MDA in children with different eNOS and IL1B genes variants. The results of the study indicate an increase in nitrate levels (5.41 vs. 2.62; p<0.001) and nitrite levels (2.69 vs. 1.39; p<0.001) in children in the recovery period of HIE. Conclusions. The detected changes were not associated with polymorphic variants of the eNOS (G894T, rs1799983) and IL1B (C3953T, rs1143634) genes. Therefore, determination of nitrate and nitrite concentrations can be implemented in clinical practice for early diagnosis and prediction of possible complications in children with HIE. Elevated levels of nitrites, nitrates and sialic acids can serve as markers of long-term consequences of hypoxic damage. The introduction of determination of nitrate and nitrite, MDA and sialic acid levels in urine, taking into account the obtained results, allows us to consider them as promising diagnostic predictors of neuropsychiatric development disorders in children.