THE EFFECT OF ENOS GENE POLYMORPHISM AND NITRIC OXIDE METABOLISM INDICATORS ON THE NEONATAL CONSEQUENCES IN PREMATURE BABIES BORN FROM MOTHERS WITH METABOLIC SYNDROME

Abstract

Metabolic syndrome is considered to be a cluster of disorders that directly contribute to the development of cardiovasculardisease and are characterized by chronic systemic infl ammation. Numerous epidemiological data indicate that an adverseintrauterine environment, caused by the peculiarities of the nutritional status or placental insuffi ciency in a woman with metabolic syndrome, can “program” the susceptibility of the fetus to further development of cardiovascular and metabolic diseases, has an impact on cognitive and behavioral development. Nitric oxide (NO) plays a critical role in the pathogenesis of components of the metabolic syndrome. Children born prematurely have a high incidence of brain damage, which can lead to motor, cognitive, behavioral, social and sensory disorders.The purpose the research was the study of the effect of the eNOS gene polymorphism and indicators of nitric oxidemetabolism on the neonatal consequences in prematurely born children from mothers with metabolic syndrome.Material and methods. A study was conducted in which 100 premature infants were included. Two groups were formed: the main group (n=34), which included preterm infants (birth weight 2145.29±148.19 g and gestational age 33.18±0.55 weeks) of mothers with metabolic syndrome, and the comparison group (n=66), which included preterm infants (birth weight 2295.99±101.45 and gestational age 34.03±0.45 weeks) of mothers without metabolic syndrome. The children underwent a genetic study – determination of the polymorphism of the eNOS gene, as well as the level of nitrites, nitrates and nitrosothiols in the urine.By decision of the bioethics commission No. 217 dated 12.06.2023, the materials of the scientifi c work comply with the Rulesof Humane Treatment of Patients.Traditional methods of parametric and nonparametric statistics were used; nonparametric methods were used to analyzequalitative characteristics expressed mainly in percentages. The methods of parametric statistics were used to check the normality of the distribution of quantitative characteristics using the Kolmogorov- Smirnov criterion.Statistical processing of the obtained results was carried out using the package of application programs EXCEL-2003® andSTATA version 11 for Windows (StataCorp, Texas, USA).The work was carried out as part of the scientifi c and experimental work of the Department of Pediatrics #1 with Neonatologyof the Poltava State Medical University “To develop clinical and laboratory criteria, methods of predicting and preventingmetabolic disoders in young children (state registration number 0120U102856).Results. The most common diseases in the infants of the studied groups were the consequences of intrauterine hypoxia(44.1%) and respiratory failure requiring artifi cial lung ventilation (50.0%), although no signifi cant diff erences were foundin the prevalence of these conditions. We identifi ed the presence of signifi cant associations between the consequences ofintrauterine hypoxia and the levels of nitrates (OR 1.19; 95% CI 1.01-1.40; p=0.042), nitrosothiols (OR 1.19; 95% CI 0.99-1.42;p=0.050) and the polymorphic genotype 4aa/ab of the eNOS gene (OR 0.28; 95% CI 0.12-0.67; p=0.004). Analysis of systemichemodynamics revealed no signifi cant diff erences in baseline values between preterm infants with and without intrauterinehypoxia, but we did observe an association with urine output on day 3 of life.To fi nally clarify the complex infl uence of indicators of nitrate metabolism on the development of intrauterine hypoxia andto predict the development of consequences of this condition in premature infants, the following indicators are included in theregression prognostic model: the level of nitrates, nitrites, 4aa/4ab genotype and urine output on the third day of life. As theresearch results show, there is a direct reliable relationship with nitrates and an inverse relationship with nitrites, 4aa/4abgenotype and urine output. This prediction model has high operating characteristics – the area under the ROC curve is 0.8168.Some mechanisms of the infl uence of maternal metabolic syndrome on the development of relevant disorders in newborns areknown, including disorders of nitric oxide synthesis, endothelial dysfunction, and oxidative stress. In our study, the consequences of intrauterine hypoxia were reliably associated with an increase in the concentration of urinary nitrates and a decrease in nitrites, as well as the absence of the 4aa/ab genotype, which is associated with reduced release of nitric oxide. There is evidence that nitric oxide can have both protective and deleterious eff ects, depending on factors such as nitric oxide synthase isoform and duration of exposure to hypoxia.Conclusions. In preterm infants born to mothers with metabolic syndrome, elevated urinary nitrate levels and the absenceof the eNOS 4aa/ab genotype increase the likelihood of suff ering the consequences of intrauterine hypoxia.