The Health Status of Newborns and Children in the First Year of Life from the High-Risk Group of Congenital Enterovirus Infection

The dissertation is dedicated to the study of the health status of newborns and children in the first year of life born into the high-risk group of congenital enterovirus infection. The research was conducted in the territory of the Republic of Sakha (Yakutia) and is aimed at establishing the risk factors of vertical transmission of enteroviruses from mother to child, as well as at assessing the clinical consequences of intrauterine infection for the health of children in the neonatal and postnatal periods. A complex of epidemiological, clinical-laboratory, and virological examination methods was employed in the work, including the determination of enteroviruses in mothers and newborns, as well as the evaluation of the effectiveness of the use of the immunomodulator "Kipferon" in complex therapy.

Relevance of the Study. In recent years, a stable and consistent decline in the infant mortality rate has been observed in the Republic of Sakha (Yakutia) and in the Russian Federation as a whole. Over the period from 2001, this indicator decreased in the Russian Federation from 14.6 per 1,000 live births to 12.4 in 2003; in the Republic of Sakha (Yakutia), it was 15.4 per 1,000 in 2002 and 13.0 per 1,000 in 2003; in 2004, it was 13.4 per 1,000. In the city of Yakutsk, it was 15.2 in 2002; 12.7 per 1,000 in 2003; 11.4 per 1,000 in 2004. However, compared with developed countries, it remains sufficiently high (8.7 per 1,000 in the United States). The reduction of the infant mortality rate is one of the foremost tasks of healthcare.

In the structure of causes of infant mortality, leading positions are occupied by diseases of the perinatal period — 42.1% (Russian Federation), 47.8% (Republic of Sakha (Yakutia)). Perinatal mortality in the city of Yakutsk was 20.0‰, and in the Republic of Sakha (Yakutia) — 15.3‰ in 2003. Therefore, the protection and study of the health of women, fetuses, and newborn children does not lose its relevance at the present time and has state significance [46, 83, 14].

An essential demographic indicator reflecting the socio-economic well-being of society, the quality and accessibility of medical care, is the mortality of children in the first year of life [23, 51].

It is known that human health is established in early childhood and is determined both by the age-related features of the growing organism and by the influence of environmental conditions (65, 15, 3, 50, 16, 5, 6].

Within the healthcare system, considerable attention is devoted to the state of pediatric care, as it is a direct reflection of the preventive direction of medicine [45, 85]. It is precisely in childhood that the foundations of severe, including chronic, adult diseases may be laid [117, 36].

The problem of intrauterine infections in modern conditions is acquiring ever greater significance in the pathology of children of early age [35, 106, 122]. In recent years, the world has noted a trend toward an apparent increase in the proportion of intrauterine infections, which depends not only on the improvement of the quality of their diagnosis but is determined by the true growth in the frequency of this pathology [108]. These diseases largely determine child mortality in the first months of life, the frequency of stillbirths; intrauterine infection substantially influences the development of the fetus and the child in subsequent years [106].

The increasing proportion of intrauterine infections (IUIs) in the pathogenesis of many pathological conditions forming in the period of childhood (minor cerebral malformations, organ dysplasia, system dysfunctions) is reported by both domestic and foreign researchers [197, 60, 206, 213, 226]. The frequency of infection of women of fertile age is increasing, both by bacteria (ureaplasmas, chlamydia) and by cytomegalovirus, herpes types I and II, transmitted by sexual contact [160, 31, 20, 89]. In the organic pathology of children, the participation of diverse agents that penetrate through the placenta (enteroviruses, influenza viruses, rubella, hepatitis B and C, parvovirus B9, mycoplasma, toxoplasma, fungi, and streptococci groups A and B) has been proven [1122].

Congenital infection in the fetus and newborn, not accompanied by the development of a vivid characteristic clinical picture of intrauterine infection, creates the possibility that it will not be diagnosed in a timely manner. In the postnatal period of the child's life, the transmitted microorganisms may lead to the impairment of the function of certain organs and a reduction in the quality of the child's subsequent life. Moreover, there is a potential danger of vertical transmission of the infectious agent, which closes the "vicious" pathological circle [108].

The Republic of Sakha (Yakutia) belongs to regions with extreme climatic conditions. In recent decades, certain successes have been achieved in the organization of the protection of motherhood and childhood, in the reduction of infant mortality indicators. At the same time, questions concerning the study of the health of children and the prevention of chronic infection in children from high-risk groups for the development of congenital enterovirus infections remain relevant and require investigation.

The study of the relationships between perinatal risk factors and the health status of children makes it possible to assess the adaptive capabilities of the child before and immediately after birth and, on this basis, to form high-risk groups and to conduct targeted preventive and therapeutic measures not only in the neonatal period but also in the postnatal period.

Objective of the Research: On the basis of establishing the risk factors of congenital enterovirus infection, to determine its influence on the health status of newborns and children in the first year of life, in order to develop and optimize measures for the prevention of the development of manifest forms of the disease.

To achieve the objective, the following tasks were set:

1. To conduct epidemiological and clinical-laboratory examination of the health status of pregnant women in the city of Yakutsk with the determination of risk factors of congenital enterovirus infection in newborns.

2. To study the health status of newborn children from the high-risk group of congenital viral infection.

3. To conduct a comparative analysis of the frequency of detection of enterovirus infection in children in the early neonatal period and their mothers.

4. To study the health status of children from the risk group of congenital enterovirus infection throughout the first year of life in catamnesis.

5. To study the clinical effectiveness of the use of the drug "Kipferon," included as an immunomodulator in the complex treatment of children, with the aim of preventing severe course of congenital infection in the postnatal period and early clinical manifestation of the disease.

Scientific Novelty

For the first time in the Republic of Sakha (Yakutia), the health status of newborn children in the first year of life from the risk group of congenital viral infection was studied. For the first time, virological examination of newborn children from the high-risk group of intrauterine viral infection and their mothers was conducted on a representative group of widely prevalent enteroviruses.

The significance of congenital enterovirus infection in the development of perinatal and postnatal pathology in children has been confirmed.

For the first time, catamnestic observation with a comprehensive assessment of the health status of newborns and children in the first year of life from the risk group of congenital enterovirus infection was conducted.

For the first time, the immunomodulatory drug "Kipferon" was used in complex treatment for the prevention of early manifestation of congenital enterovirus infection.

The highest frequency of the formation of deviations in the health status of children in the presence of viral-viral associations in mothers has been demonstrated.

Practical Significance of the Research

The results of the conducted research confirmed the significance of enteroviruses in the etiology of congenital infection.

The necessity of implementing the indirect immunofluorescence method for the diagnosis of congenital enterovirus infection in children in the early neonatal period, in whose maternal history there are indicators of high risk of vertical transmission of this infection, in obstetric institutions has been demonstrated.

The drug "Kipferon" is recommended for inclusion in the complex treatment of children in the first year of life with clinical manifestations of congenital viral infection, as an immunomodulator.

Implemented in practice:

Based on the materials of the research, an informational letter "Diagnostic Algorithm and Principles of Therapy of Individual Conditions and Diseases of the Neonatal Period" (Yakutsk, 2005) was developed, which is used in the practical activities of obstetric institutions and healthcare and preventive institutions of the Republic of Sakha (Yakutia).

The results of the work are used in the process of training students of the pediatric and therapeutic faculties and listeners of the faculty of postgraduate education of physicians of the Medical Institute of the Yakutsk State University named after M.K. Ammosov.

The following propositions are to be defended:

1. Enterovirus infection of a pregnant woman is an etiological factor in the development of pathology in the newborn child and in children in the first year of life.

2. Viral-viral associations of Coxsackie A and ECHO underlie the development of perinatal pathology in newborn children.

3. The inclusion of "Kipferon" in the complex treatment of patients in the first year of life leads to a clinical improvement in the health status of children.

Structure and Volume of the Dissertation