THE FREQUENCY AND STRUCTURE OF CONGENITAL MALFORMATIONS IN RURAL POPULATIONS OF SOUTHERN UKRAINE AND THE ROLE OF GENETIC AND DEMOGRAPHIC FACTORS IN THEIR DISTRIBUTION

In modern conditions of constant population decline and the presence of adverse demographic processes in Ukraine, the urgent task is to identify the most significant genetic and demographic factors affecting the adaptation of the population, as well as monitoring changes in the volume and structure of the genetic load caused by congenital pathology. The frequency of congenital malformations of newborns in the Kherson region increased (from 22.3±5.4 % in 2000-2008 to 40.1 ± 8.2 % in 2009-2017). In recent years, there has been a statistically significant increase in the frequency of hereditary pathology of newborns among the rural population of the region (from 1.09 to 1.95 %). The total frequency of congenital malformations increased in almost all areas of the Kherson region (from 20.2±1.4, 27 to 27.6±1.3 %) and averaged 30.2±6.4 %. Significant differences in this indicator were found between some nations of the region. Malformations of the circulatory system (28.5 %), musculoskeletal system (26.05 %) and the genitourinary system (15.25 %) occupy a leading place in the structure of congenital pathology. The prevalence of congenital malformations is inversely correlated with the prevalence of spontaneous miscarriages (r =-0.52± ±0.12; tr=2.4> t05=2.12), which indicates the presence of a screening effect that eliminates non-viable genotypes in embryonic period of ontogenesis. Rural population where the share of interethnic marriages has increased over the years of research, is characterized by a higher prevalence of congenital malformations (r=0.50±0.46; t=2.3>t05=2.12). In population (with an endogamy index of 0.5 and higher), an increase or relative constancy of the proportion of homolocal mono-ethnic Ukrainian marriages and a lower prevalence of congenital malformations among newborns are observed. The level of endogamy does not significantly affect the prevalence of malformations (r=-0.20±0.24; tr=0.8<t05=2.12). A promising area of research is the study of the causes of differences in the prevalence of congenital malformations among the rural population of the same region with an analysis of the characteristics of the formation of their ethnic structure.

In modern conditions of constant population decline and the presence of adverse demographic processes in Ukraine, the urgent task is to identify the most significant genetic and demographic factors affecting the adaptation of the population, as well as monitoring changes in the volume and structure of the genetic load caused by congenital pathology. The frequency of congenital malformations of newborns in the Kherson region increased (from 22.3±5.4 % in 2000-2008 to 40. 1 ± 8.2 % in 2009-2017). In recent years, there has been a statistically significant increase in the frequency of hereditary pathology of newborns among the rural population of the region (from 1.09 to 1.95 %).
The total frequency of congenital malformations increased in almost all areas of the Kherson region (from 20.2±1.4, 27 to 27.6±1.3 %) and averaged 30.2±6.4 %. Significant differences in this indicator were found between some nations of the region. Malformations of the circulatory system (28.5 %), musculoskeletal system (26.05 %) and the genitourinary system (15.25 %) occupy a leading place in the structure of congenital pathology. The prevalence of congenital malformations is inversely correlated with the prevalence of spontaneous miscarriages (r =-0.52± ±0.12; tr=2.4> t05=2.12), which indicates the presence of a screening effect that eliminates non-viable genotypes in embryonic period of ontogenesis.
Rural population where the share of interethnic marriages has increased over the years of research, is characterized by a higher prevalence of congenital malformations (r=0.50±0.46; t=2.3>t05=2.12). In population (with an endogamy index of 0.5 and higher), an increase or relative constancy of the proportion of homolocal mono-ethnic Ukrainian marriages and a lower prevalence of congenital malformations among newborns are observed. The level of endogamy does not significantly affect the prevalence of malformations (r=-0.20±0.24; tr=0.8<t05=2.12).
A promising area of research is the study of the causes of differences in the prevalence of congenital malformations among the rural population of the same region with an analysis of the characteristics of the formation of their ethnic structure.
Research relation to the programs, plans, and department themes. The research is carried out within the framework of the university research work "Directivity of genetic and demographic processes in conditions of depopulation of the south of Ukraine", state registration number 0112U004273.
Introduction. Birth defects represent a diverse group of disorders of prenatal origin that can be caused by defects in a single gene, chromosomal abnormalities, multifactorial inheritance, ecological teratogen, micronutrient deficiency and maternal infections. Congenital anomaly is a defect in morphogenesis in early embryogenesis. Congenital malformations usually prevailed in children born of consanguinity [1].
Taking into account the fact that most cases of congenital malformations among all pregnancy outcomes occur in live births, it is the assessment of the prevalence of congenital malformations among living newborns, and not all births that is the most acceptable form of analysis of epidemiological data [3].
The basis of medical and genetic preventive measures aimed at reducing the burden of congenital malformations, chromosomal and genetic diseases is an accurate knowledge of their prevalence in the region, taking into account the population genetic structure of the population, geographical, environmental and hygienic features territories and quality of medical care to the population [4].
The general prevalence of congenital malformations, their structure and the frequency of some specific malformations are different in different maternal ethnic groups. A study of the prevalence and structure of congenital malformations in different ethnic groups can become the basis for etiological studies and health planning [5].
In modern conditions of constant population decline and the presence of adverse demographic processes in Ukraine, the urgent task is to identify the most significant genetic and demographic factors affecting the adaptation of the population, as well as monitoring changes in the volume and structure of the congenital pathology. The intensity and direction of population transformations should be investigated in the context of the three components of their dynamics: influences on this process of factors of microevolution, genetic-demographic parameters, epidemiology of hereditary and congenital pathology [6].
There are significant differences in the frequency and structure of congenital malformations in newborns in different regions of Ukraine. In the western region and in the northern part of Ukraine in the structure of congenital malformations of newborns the first place is occupied by defects of the musculoskeletal system, in the southern part of Ukraine the main are defects of the cardiovascular system. In the Chernivtsi region the frequency of defects and deformations of the musculoskeletal system exceeds the data both in Ukraine and in other countries approximately by 2.7 times [7].
The presence of differences in the frequency and structure of congenital malformations of newborns in certain regions of Ukraine and in different countries of the world can serve as evidence of the genetic and demographic conditionality of congenital malformations among the causes of their prevalence [4]. However, the question of exactly which factors of the dynamics of the population structure affect the prevalence of congenital pathology and how much this effect is significant remains unresolved.
Material and methods. The study was conducted in accordance with the main criteria of the EUROCAT European Register [8]: 1) conducting research in limited populations (accounting for newborns with developmental abnormalities whose parents live in a given locality); 2) accounting for 19 nosological forms.
When calculating the frequency of malformations of the population of Kherson region, we used the materials of the regional medical-statistical register on the total number of newborns born alive and stillborn, as well as on the birth of children with developmental disabilities, subject to strict registration (medical form 21, 13, 49). The obtained data were processed using standard statistical methods: the calculation of the standard deviation of the error of the mean, the error of the arithmetic average of the characteristic. Statistical calculation of the obtained results (calculation of confidence intervals and the reliability of differences) was carried out using the programs STATISTICA and Microsoft Excel 9-2000.
In order to analyze the influence of certain parameters of the genetic and demographic structure (the level of interethnic marriages, the endogamy index) on the prevalence of congenital malformations and early spontaneous miscarriages among the population of the district populations of Kherson region, the Spearman correlation coefficient between these parameters was calculated. The significance of the differences was evaluated using Student's t-test.
Results and discussion. In Kherson region, isolated single congenital malformations (97.7%) had the largest share and only 2.3% were multiple, including chromosomal abnormalities. In the conditions of reduction of the population of Kherson oblast and reduction of fertility rate, the frequency of congenital developmental defects among newborns has increased (from 22.  Table 1). The frequency of genetically determined congenital malformations was significantly higher (1.33± ±0.018%) than the average in Ukraine (0.99±0.014%) in Kherson region for the period of 2002-2015. In recent years, there has been a statistically significant increase in the frequency of hereditary pathology of newborns in the rural population of the region (from 1.09 to 1.95%).
The proportion of multiple malformations in the overall structure of congenital malformations was 2.27%. In the group of defects with multiple lesions of systems and organs, the proportion of cases with chromosomal pathology and syndromes of other etiology was almost the same -8.0% and 9.1%, respectively.
In recent years, a statistically significant increase in the frequency of congenital malformations of the circulatory system among all other nosological groups has been observed in Kherson region (from 23.7% for the period of 2000-2006 to 38.3% for the period of 2007-2017). We noted a slight decrease in the fre-quency of gastrointestinal malformations (from 3.75% to 3.6 %), defects of the nervous system (from 3.0 % to 2.4 %). The frequency of malformations in the development of the urinary organs has remained at the same level (15.5-15.0 %). A particular concern is the increase in prevalence in populations of congenital malformations caused by chromosomal aberrations (from 4.2 to 5.3 %) and multiple developmental malformations (from 2.1 to 3.4 %).
Conclusion and future perspectives. In the context of a decrease in the population of Kherson region and a decrease in the birth rate, the frequency of congenital malformations in newborns increased (from 22.3±5.4 % in 2000-2008 to 40.1±8.2 % in 2009-2017). Significant differences in this indicator were found in the population of the region. The dynamics of the frequency of congenital malformations can be used to assess the adaptive homeostasis of populations under conditions of their genetic and demographic transformation.
The decrease in the frequency of reproductive losses is accompanied by a statistically significant increase in the prevalence of congenital malformations in the population, which can be explained by the selective effect of the "sifting" selection during the period of fetal development (r=-0.52±0.12; tr=2.4> t05=2.12).
The study of dynamics of the structure of congenital malformations showed a statistically significant increase in the prevalence of congenital malformations of the circulatory system among newborns (from 23.7% in the period of 2000-2006 to 35.3% in the period of [2007][2008][2009][2010][2011][2012][2013][2014][2015]. Rural population where the share of interethnic marriages has increased over the years of research is characterized by a higher prevalence of congenital malformations (r=0.50±0.46; t = 2.3> t05=2.12), which confirms the validity of the idea of possible negative consequences of outbreeding (violation of adaptive gene complexes, increased recombination rate).
Rural population (endogamy index 0.5 and higher) having an increase or relative constancy of the share of homolocal mono-ethnic Ukrainian marriages is characterized by a lower incidence of congenital malformations among newborns (17.7±3.4: 19.3±3.0 %, respectively) compared with population where the proportion of such marriages has significantly decreased (28.1 ± 4.4) %.
The authors of this study confirm that the research and publication of the results were not associated with any conflicts regarding commercial or financial relations, relations with organizations and/or individuals who may have been related to the study, and interrelations of coauthors of the article. Стаття надійшла 01.08.2019 р. Рекомендована до друку на засіданні редакційної колегії після рецензування