Multiple organ failure (MOF) is the leading cause of neonatal mortality in intensive care units. The prevalence of MOF in newborns is currently unclear, since its incidence varies in asphyxia, sepsis, prematurity, and comorbidity, and depends on the level of development and funding of health care in different countries. Sepsis and acute respiratory distress syndrome prevail among the causes of MOF in this category of patients.Aim of the review. To summarize the available literature data on the pathogenesis, therapeutic strategies and outcomes of MOF in newborns.Material and methods. We searched PubMed, Scopus, Web of Science, and RSCI databases using the following keywords: «newborns, multiple organ failure, etiology, pathogenesis, premature, diagnosis, treatment, respiratory support, cardiotonic support», without language limitations. A total of 144 full-text sources were selected for analysis, 70% of which were published in the last five years and 50% were published in the last three years. Criteria for exclusion were low information value and outdated data.Results. The prevalence of MOF in neonates is currently unclear. This could be due to common association of neonatal MOF (as well as the adult one) with various diseases; thus, its incidence is not the same for asphyxia, sepsis, prematurity, and comorbidities. There is no precise data on neonatal mortality in MOF, but according to some reports, it may be as high as 13-50%.In newborns, MOF can be caused by two major causes, intrapartum/postnatal asphyxia and sepsis, but could also be influenced by other intranatal factors such as intrauterine infections and acute interruption of placental blood flow.The key element in the pathogenesis of neonate MOF is cytokinemia, which triggers universal critical pathways. Attempts to identify different clinical trajectories of critical illness in various categories of patients have led to the discovery of MOF phenotypes with specific patterns of systemic inflammatory response. This scientific trend is very promising for the creation of new classes of drugs and individual therapeutic pathways in neonates with MOF of various etiologies.The pSOFA scale is used to predict the outcome of neonatal MOF, however, the nSOFA scale has higher validity in premature infants with low birth weight.Central nervous system damage is the major MOF-associated adverse outcome in newborns, with gestational age and the timing of treatment initiation being key factors affecting risk of MOF development in both full-term and premature infants.Conclusion. The study of cellular messengers of inflammation, MOF phenotypes, mitochondrial insufficiency, and immunity in critically ill infants with MOF of various etiologies is a promising area of research. The pSOFA scale is suggested for predicting the outcome of MOF in full-term infants, while the nSOFA scale should be used in premature infants with low birth weight.

The problem of persistent critical illness (PCI) in newborns is poorly understood. The epidemiology of this pathological condition in newborns has not been precisely established, however, it is known that PCI is considered a predictor of an unfavorable outcome in any pathology and proceeds more severely then in adults and children. Long-term outcomes of PCI in surviving newborns are associated with subsequent asthenia, cognitive impairment, chronic fatigue syndrome, a high incidence of disability, complex physiological abnormalities, and chronic organ dysfunction from which they rarely recover.Nutritional, respiratory and hemodynamic supports are key components of neonatal PCI therapy. The physiology of a newborn is different from that of an adult patient; therefore, inotropic therapy in this category of patients requires special approaches. In the past few years, in addition to dopamine, dobutamine and adrenaline, newborns have been prescribed milrinone, norepinephrine, vasopressin, and levosimendan as hemodynamic support. The clinical potential of these drugs in neonates is still under evaluation but there is some evidence for their benefits for use in PCI.

The problem of intensive shock therapy of various etiologies in neonatology remains relevant. Anatomical and physiological features of the cardiovascular system and changes that occur during the first weeks of life in children affect the choice and dose of drugs to resolve a critical condition. The shortcomings of medications available in neonatology for the correction of arterial hypotension and shock led to the search for new drugs for the treatment of such patients.Levosimendan is a cardiotonic agent that increases the sensitivity of the heart to calcium, has a positive inotropic and vasodilatory effect, reducing preload and postload of the heart. Levosimendan has been used in neonatal practice for more than 15 years, but the lack of major studies to date evaluating its effectiveness and safety in newborns significantly limits its use. Several studies have demonstrated a positive effect of the drug on cerebral, systemic perfusion and oxygenation in newborns with low cardiac output syndrome, safety, low frequency of side effects and reduced time spent in the intensive care unit for newborns after correction of heart defects and in newborns who have suffered asphyxia. However, most of the published results of the clinical use of levosimendan in neonatology are limited to a few observations or poor quality of the study design.The available literature data indicate a good potential of the drug as a means of inotropic support, however, there is no convincing data on the effect of levosimendan on the survival of newborns in critical condition.