MODERN MODEL OF GENETIC MONITORING AS A PROMISING TOOL FOR REDUCING INCIDENCE OF GENETIC PATHOLOGIES IN UKRAINE
NOWOCZESNY MODEL MONITORINGU GENETYCZNEGO JAKO OBIECUJĄCE NARZĘDZIE REDUKCJI WYSTĘPOWANIA WAD GENETYCZNYCH NA UKRAINIE
Dmytro O. Mykytenko1,2, Tetiana S. Gruzieva1
1Bogomolets National Medical University, Kyiv, Ukraine
2Clinic of Reproductive Medicine «Nadiya», Kyiv, Ukraine
Introduction: The medical and social substantiation of an optimized system of genetic monitoring in Ukraine for providing of quality medical care with economic substantiation should be developed for quality medical care and justification of budget expenditures and the economic evaluation of the effectiveness of treatment and prevention measures.
The aim is to develop a modern model for the genetic monitoring and provide substantiation of the measures for the prevention of hereditary transmission of genetic defects and birth of children with congenital defects.
Materials and methods: The following research methods have been employed: systematic approach and analysis technique; bibliographic and semantic method; method of conceptual modeling.
Conclusions: The model of genetic monitoring with the modern concepts of healthcare reform in Ukraine has been developed taking into account the priorities of the state health policy, modern internationally recognized and recommended by WHO.
Key words: genetic monitoring, model, genetic pathologies, genetic load
Wiad Lek 2019, 72, 2, 169-174
Prolonged period of unfavorable socio-economic and political climate in Ukraine, stagnation of economy and deterioration of environment resulted in the exacerbation of the country’s demographic crisis and aggravation of the general situation in healthcare system. Although WHO data indicate a weak tendency towards the stabilization of the situation over the last years (crude mortality rate fell from 16.66 per 1000 persons in 2005 to 14.76 in 2014, total fertility rate increased from 1.1 in 2001 to 1.5 in 2013, life expectancy at birth grew from 67.3 in 2005 to 71.44 in 2014), mid-year population is still decreasing at a rate of 0.7±0.3%/year starting from 1994, the number of born living, that increased between 2001 and 2008 from 7.71 to 11.8 per 1000 persons, is nearly stable, the share of over-65 population demonstrates intermittent growth from 11.3% in 1986 to 15.47% in 2014 . These data give no promise that a demographic problem could be solved in mid-term perspective.
Also, a slight intermittent tendency to the increase in the number of children with birth defects, from 22.21 in 2004 to 23.16 in 2013 per 1000 liveborn children, along with reduced probability of dying in the first five years of life from 21.83 in 1981 to 9.46 in 2014 per 1000 liveborn children (2.3-fold), and reduction in infant death from 16.23 in 1981 to 7.85 in 2014 per 1000 liveborn children (2.07-fold)  are indicative of the following: а) improved quality of medical care and provision of a chance at survival for those children who would have not had this chance otherwise; b) withdrawal of a number of pathological conditions from the influence of natural selection, which will promote the gradual accumulation of the relevant pathologies and necessitates the introduction of an effective system of genetically-predisposed pathologies monitoring in order to counteract further increase in genetic load. Infertility is one of the manifestations of genetic load, since diseases with a genetic component are characterized by impaired fertility and increased risk of birth defects . According to WHO, the share of sterile marriages is 15-20%.
Thus, there is an urgent need in the introduction of an effective genetic pathologies monitoring system in order to prevent further increase of genetic load in Ukraine. However, in view of the permanent reforming of the healthcare system, the latest vectors of which have been approved by the law of Ukraine “On State Financial Guarantees of Public Health Care” dated 19.10.2017, and set-aside resolution of the issues related to thefinancing of secondary and tertiary levels of medical care, it is extremely important to develop the model that could be integrated into the healthcare system at any stage of its reforming.
The objective of this research is to develop a modern model for the monitoring of genetic pathologies and provide scientific substantiation of the measures aimed at prevention of hereditary transmission of genetic defects and birth of children with congenital defects.
Materials and Methods
Data from scientific literature and statistical reports by WHO have been used as information basis for this research.
The following research methods have been employed:
– systematic approach and analysis technique was used at all stages of research in order to address specified tasks;
– bibliographic and semantic method was used to study and analyze data from scientific literature with regard to the problem under investigation;
– method of conceptual modeling was employed to develop the model of genetic monitoring system.
Results and Discussion
It has been established that the rate of congenital malformations in Ukraine exceeds the average rate seen in Europe, which is characteristic of the countries with low living standards. Since the infertility and congenital abnormalities have multifactorial etiology, their control should focus on the internal (genetic predisposition) and external controllable factors [3,4]. To achieve a productive goal, the provisions of Art. 29 of the Law of Ukraine “Fundamentals of Healthcare Legislation of Ukraine” on the organization of the genetic monitoring should be fulfilled. However, as seen from the analysis of legal frameworks and the current state of medical genetic service, there are problems in the provision of genetic counseling services (GCS) to the population of Ukraine. Given the urgency of the issues of genetically-predetermined pathologies control, rising incidence of such conditions, problems associated with regulatory support and provision of resources for medical genetic service, and the need for improvement of its operation, the optimized system of genetic monitoring and its functional and structural model have been substantiated (Fig. 1, 2).
Priorities of the state health policy, current internationally recognized and recommended by WHO strategies of genetic monitoring, and existing problems and needs identified in the previous research have been used as a basis for the formation of optimized model of genetic monitoring [5; 6].
It has been determined that optimized genetic monitoring system aims at prevention, timely identification and correction of genetically predetermined pathologies, provision of high quality and accessible GCS, reduction of genetic load, and prevention of resulting medical, social and economic losses.
Planning and monitoring of chromosomal and other genetic pathologies, analysis of data obtained from research and surveys, management decisions, provision of services, assurance and assessment of their availability and quality, evaluation of medical, social and economic efficiency are considered to be the main areas of activity of genetic monitoring system.
The proposed model consists of numerous structural components and their inherent functions, including organizational and managerial, coordination, scientific, educational, methodological, communicative, research and information, regulatory and resource support. Each structural component is responsible for the implementation of the functions established under the system of genetic monitoring, with extensive cross- and intra-sectoral relations.
This model includes institutions and organizations involved in the performance of genetic monitoring, their functions, components of the system of provision and organization of work; it establishes the stages for monitoring of genetic disorders and introduces a new analytical framework in charge of the collection, processing and analysis of information, evaluation of performance indicators and development of recommendations aimed at improvement of genetic pathologies prevention.
The feature of this model is that it includes existing elements of genetic counseling system, partially modified elements and qualitatively new ones. (Fig. 3).
The existing elements incorporated in the developed model without changes of their functions include those in charge of regulatory, resource and scientific support, management and coordination, in particular the Supreme Council of Ukraine, Cabinet of Ministers of Ukraine, central executive bodies, the main of which are MoH of Ukraine, Ministry of Education and Science of Ukraine, Ministry of Social Policy of Ukraine, Ministry of Economic Development and Trade of Ukraine, Ministry of Ecology and Natural Resources of Ukraine, State Statistics Service of Ukraine and local executive bodies and local authorities. The function of scientific support is performed by the institutions and organizations of the MoH and NAMS of Ukraine with such relevant agencies as the State Institution “Institute of Congenital Pathologies” of NAMS of Ukraine and State Institution “O. M. Marzeiev Institute of Public Health” of NAMS of Ukraine; the function of communications support is performed by relevant institutions and mass media.
A qualitatively new element to be implemented is Information Analysis Center of Genetic Monitoring which establishment under the MoH of Ukraine is deemed appropriate. The main tasks of the Center should be the collection, processing, analysis of data obtained during the genetic monitoring, followed by assessment of the main criteria of its effectiveness: indicators of medical, economic and social efficiency. According to the WHO concept, three groups of indicators are used to characterize the quality of medical care: indicators of structure, process and final results of provided care.
The clinical efficacy of the monitoring of genetic disorders will involve the reduction in reproductive losses and child mortality, improved diagnosis, modification of the structure of congenital pathologies in newborns in favor of less-disabling diseases.
Social efficiency can be estimated by the reduced share of genetic diseases in the disability causes and reduced overall level of childhood disability, increased satisfaction of the population with the quality of medical care.
In contrast to the existing system of genetic monitoring, the new model involves assessment of the economic efficacy of the measures taken. According to the calculations made in the study, the medical outcome of the previous 5-year genetic monitoring program that took place in Kyiv was 8.1% reduction of reproductive losses among registered pregnancies. The economic efficacy forecast for the implementation of genetic monitoring program at the national level has been calculated using the extrapolation method. Based on the previously calculated reproductive fetal losses and economic equivalent of the cost of living (in the form of profit of the state budget resulting from person’s activities) [2; 7; 8; 9], the expected reduction in the number of reproductive losses with the implementation of genetic monitoring program has been evaluated as3477.2±160.5 cases per year, the cumulative profit of the state budget – UAH 21603.2±997.1 million or USD 1716.4 ± 79.2 million, taking into account the purchasing parity.
Optimization of other components of the model is logically related to the organization of a new information analysis link and modification of methodical approaches to neonatal screening. Introduction of such changes requires improved system of provision of resources for genetic monitoring. Firstly, proper staffing and improvement of pre- and postgraduate training of specialists in population genetics, public health, laboratory diagnostics, professional topic-specific development of physicians of healthcare institutions of I-II levels, primarily general practitioners-family physicians, obstetricians-gynecologists and pediatricians.
To ensure the functioning of the information analysis center, scientific and methodological support of its operation within the organizational hierarchy should be provided. The best is to put the feedback and efficacy assessment unit under the control of the Ministry of Healthcare of Ukraine in order to receive, process, save and analyze the reporting information of health departments of local authorities and bodies of local self government developed on the basis of reports of healthcare institutions. This unit should be responsible for the evaluation of medical, social and economic efficacy of the measures that have been taken and involves the use of modern information and application systems. Analytical results will serve as the basis for improvement of the structure, organization, provision of resources for the process of genetic disorders monitoring.
According to the proposed model of genetic monitoring system, the major role in the identification of risk factors of genetic pathologies in patients (as per art. 2.2 of the Guidelines on the organization of provision of medical and genetic assistance, approved by the Order of the MoH of Ukraine dated 31.12.2003 No. 641/84) is assigned to the primary care physicians of “first medical contact” (general practitioners-family physicians, pediatricians, primary care doctors, obstetrician-gynecologists) that subsequently refer patients to medico genetic institutions of respective region. The above requires modification of occupational characteristics of positions in the corresponding specialties. The programs of individual prevention of hereditary transmission of genetic abnormalities should be developed with the involvement of experts in reproductive genetics, obstetricians-gynecologists, taking into account the possibilities of preimplantation and prenatal diagnosis. The prophylaxis of chromosomal and other genetic pathologies at the level of population should be performed on the basis of interagency interaction and under coordination of information analysis center of genetic monitoring.
Thus, the proposed model of genetic monitoring, unlike the existing one, is based on the cross-sectoral approach, includes modern information analysis center with wide range of functions, including evaluation of medical, social and economic efficacy of the measures taken with due consideration to the opinions of service providers and users, powerful system of e-healthcare on the basis of eHealth, involves the cooperation with the State Institution “Center of Public Health of the MoH of Ukraine”, its regional branches, local executive bodies and local authorities, training of specialists in public health and population genetics, expansion of preventive functions of primary healthcare institutions with regard to initial genetic counseling, enhancement of communication relations and has a clear focus on prevention.
Improvement of genetic pathologies prevention as a strategic direction of healthcare activities will give the opportunity to reduce the load of genetic diseases and decrease significant costs incurred by the citizens and the state as a whole, achieve improvement of public health and sustainable use of resources under the conditions of competing priorities. The outlined goals are extremely important as the healthcare faces numerous challenges and threats and is subject to significant resource constraints. Under such conditions, the prevention of genetic pathologies is not only a social but also an economic necessity, and requires strict state and public control.
Based on the research findings, the following priority measures aimed at improvement of genetic monitoring have been identified, which need to be implemented within the framework of the proposed functional and structural model:
– extension of the list of conditions that are subject to additional reporting and analysis within genetic monitoring in order to assess the state of the population’s gene pool, along with registration of cases of primary sterility, spontaneous abortions (especially during the first trimester of gestation, when the share of lethal mutations, primary genomic and chromosomal, is over 50%), perinatal death, multiple pregnancies, birth of children with congenital abnormalities, and evaluation of the weight and growth of newborns and their sex distribution;
– establishment of national registers of reproductive losses, congenital and hereditary pathologies, infertile couples and results of screening of germ cells donors for the genetic pathologies;
– extension of genetic monitoring to include pregnant women, newborns, adolescents≤ 17 years of age;
– supplementing the screening programs for pregnant women at high risk with tests for chromosomal abnormalities and fetal malformations by introducing reimbursement of expenses associated with the performance of non-invasive tests for chromosomal abnormalities of the fetus using the blood of pregnant woman and invasive types of genetic diagnosis;
– establishment of the system for reimbursement of the costs associated with embryos PGD to the carriers of genetic pathologies, which proved to be effective for the individual prevention of the inheritance of genetic mutations (genomic, chromosomal, gene);
– vesting of primary healthcare centers’ physicians (general practitioners-family physicians, obstetricians-gynecologists, pediatricians, and primary care doctors) with the functions of identification of risk factors and possible manifestations of chromosomal or other genetic pathologies;
– transition from neonatal screening methods based on immuno-fluorescence analysis for 4 diseases to the methods of mass spectrometry covering over 30 medical conditions and characterized by lower cost of examination;
– enhancement of the preventive focus of genetic monitoring measures and provision of medical and genetic services, implementation of the preventive health promotion strategy of the WHO, which envisages modification of people’s physical activity, dietary habits, restriction of influence and prevention of negative effects of external factors in the development of multifactorial pathologies, enabling some individuals and communities to control the factors that shape the health;
– development of legal framework of healthcare system and settlement of issues of genetic monitoring application in the context of government reform and enhancement of local administrations;
– improvement of training degree of physicians in medical genetics, provision of access to scientific electronic databases and information resources;
– creation of common medical and information area, formation of e-health system, which will expand the opportunities for the establishment of proposed registers.
The development and implementation of the special-purpose state medical and social genetic monitoring program in Ukraine for 2019-2023 is an important component of improving the provision of genetic counseling services to the population.
This research addresses a very important applied research task concerned with substantiation of improvement of genetic pathologies prevention by implementation of modern functional and structural model of genetic monitoring system in Ukraine in the context of socio-economic transformations and resource constraints. The model, unlike the existing one, is based on the cross-sectoral approach, includes modern information analysis center with wide range of functions, including evaluation of medical, social and economic efficacy with due consideration to the opinions of service providers and users, powerful system of e-healthcare on the basis of eHealth, involves the cooperation with the State Institution “Center of Public Health of the MoH of Ukraine”, its regional branches, local executive bodies and local authorities, training of specialists in public health and population genetics, expansion of preventive functions of primary healthcare institutions with regard to initial genetic counseling, enhancement of communication relations and has a clear focus on prevention. Implementation of genetic monitoring program has potential medical effect amounting to 3477.2±160.5 prevented cases of reproductive losses, and economic effect of UAH 21603.2±997.1 million or USD 1716.4 ± 79.2 million of state budget profit per 1 year of implementation as a national special-purpose program.
A set of actions aimed at improvement of genetic pathologies prevention has been developed, including the measures at the national, sectoral and regional levels to be implemented by the scientific institutions of the National Academy of Medical Sciences of Ukraine, institutions of pre- and postgraduate education of the MoH of Ukraine and Ministry of Education and Science of Ukraine, practical healthcare institutions, in particular, extension of the list of genetic conditions that are subject to reporting, application of genetic monitoring to adolescents ≤ 17 years of age, reimbursement of the costs associated with genetic testing for some categories of patients within the framework of the system of compulsory (state) social health insurance, modification of the approaches to neonatal screening, improved involvement and degree of training for physicians of primary care setting, and etc.
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7. Mykytenko DO, Lynchak OV, Tymchenko OI. Genetic Load in the Populations of Ukraine: congenital and hereditary pathology. Woman’s Health: Journal of Research and Practice. 2012,10(76):17-21.
8. Mykytenko DO, Tymchenko OI, Lynchak OV. Genetically Dependent Reproductive Losses: economic aspect. Hygiene of populated places. 2012,60:342-346.
9. Tymchenko ОІ, Lynchak OV, Protsiuk OV et al. Gene pool and health: natural and artificial selection in the population of Ukraine. Kyiv, State Institution “O.M. Marzeiev Institute of Hygiene and Medical Ecology NAMSU”, Medinform»; 2015, p. 163.
The scientific work was carried out within the framework of scientific research projects of the SI “Institute of Hygiene and Medical Ecology named after A. M. Marseev, NAMS of Ukraine” and State Program “Health of the Nation”. Themes of projects: “Estimation of the possible impact of habitat on radioactive contaminated and “clean” territories on the state of the population gene pool” (ДП 20.10, № 0110U001465), ‘Influence of selection processes on population reproduction in Ukraine’ (АМН.Ф.07.12, № 0112U001052). Theme of project of SI “National Scientific Center for Radiation Medicine, NAMS of Ukraine”: “Investigation of the factors of female and male infertility in the remote period after the accident at the Chernobyl Nuclear Power Plant” (510, № 0111U000755). Theme of project of International Scientific and Technical University named after academician Yuriy Bugay: “Formation, increase and rational use of strategic potential of Ukraine” (№0111U009268).
According to the order of the Authorship.
Conflict of interest:
The Authors declare no conflict of interest.
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Fig. 1. Modern structural and functional model of genetic monitoring system in Ukraine
Fig. 2. Conceptual diagram of comprehensive interagency system of prevention of chromosomal and other genetic pathologies in the population
Fig. 3. Main elements of implementation of modern model of genetic monitoring system