Analysis of the Causes of Cerebral Palsy in Kazakhstan

Introduction: Cerebral palsy is the most common childhood disability Aims: Analyze and determine the main risk factors for the development of cerebral palsy in the population of Kazakhstan Materials and methods: Retrospective, analytical "case" "control". Core group "case" medical records of 100 pregnant women whose children at different ages has been diagnosed with cerebral palsy Results: Thus, a retrospective analysis revealed the following features and complications in the perinatal period, which could promote the formation of cerebral palsy in children. Analytical results of the study are set significant results in cerebral palsy development Conclusion: Premature birth and urinary tract infections turned out to be the largest contributors to the development of cerebral palsy, however, according to statistics, the rate of preterm birth, as well as the detection of infections, stably remains at the same level, while the number of cerebral palsy has been steadily growing since the early 1990s in Kazakhstan.


Introduction
Cerebral palsy (CP) is the most common childhood disability. [1][2][3] Over the past decade, important discoveries have been made in the field of early diagnosis, prevention and treatment, which have influenced the incidence, prognosis and effectiveness of treatment.
CP is the most common physical disability in childhood, but cerebral palsy is not a purely childhood cause of disability, as most people with cerebral palsy survive into adulthood. [4] CPis a general term for a clinically and ethologically heterogeneous group of persistent, but not unchanged, movement and / or posture disorders. Epilepsy, as well as cognitive, sensory and behavioral disorders, often accompany this movement disorder. [5,6] Infections such as toxoplasmosis, rubella, cytomegalovirus and herpes simplex virus during pregnancy have been associated with an increased risk of cerebral palsy [3,19,20], but these agents account for only a small proportion of CP cases in SVD. Objectives of this work to analyze and determine the main risk factors for the development of cerebral palsy in the population of Kazakhstan

Materials and Methods
Retrospective, analytical "case" -"control". Core group "case" -medical records of 100 pregnant women whose children at different ages has been diagnosed with cerebral palsy, a control group of 200 pregnant women -respectively, the diagnosis of cerebral palsy in children is excluded.
There was conducted retrospective analysis of 300 histories of genera, the history of neonatal development, metabolic women cards drawn from Almaty maternity homes in the period from 2003 to 2019. The diagnosis of cerebral palsy was established in age from 3 months to 10 years.
We studied the clinical and medical history, laboratory data, peculiarities of pregnancy and childbirth, newborn condition at birth.
Results of the analysis of medical records of women and children used for analytical study, in the setting of maternity homes/offices and perinatal centers

Results
This section may be divided by subheadings. It should provide a concise and precise description of the experimental results, their interpretation, as well as the experimental conclusions that can be drawn.

Kazakhstan
Statistical data disability in any country is one of the most important medical and social health indicators, while reflecting the level of socio-economic development of society, environmental conditions and the quality of preventive measures.
Despite the relatively low incidence (81.4 per 100,000) of cerebral palsy in Kazakhstan compared to developed countries [6,[21][22][23], the country has seen an increase in cases over the past 30 years (Figure 1), although in other countries, on the contrary, there has been a decrease. [2]

Analysis results
The average age of the patients of the main group was 26.6 ± 1.9 years in control group 24.8 ± 1.7 years, significant differences were not detected. Thus, in the study and control group of genera occurred in patients of reproductive age.
It is known that the concomitant extragenital diseases are unfavorable backdrop to the course of pregnancy and childbirth, as well as state of intrauterine fetus and newborn. From extragenital diseases frequency kidney and urinary tract diseases were significantly more (p <0.001) were observed in patients of the main group (36,4 ± 1,7)%, whereas in the control group this index was 17,0 ± 2,1%.
One of the factors that affect the course of pregnancy and childbirth is a gynecological disease. From the analysis it follows that gynecological diseases significantly (P <0.001) more frequently detected in patients of the main group. Thus, chronic inflammation of the uterus, cervical erosion is more than 3 times more frequent in patients of the main group (19 ± 2,1% and 6.0 ± 2.7%, respectively) compared with the control. It draws attention to the high frequency of abortions in patients of the main group 27%, compared with women in the control group of 8%.
Characteristics of menstrual function showed that the average age of menarche at pregnant women and control group had no significant difference and amounted to 13.4 ± 1.5 years and 12.8 ± 1.4 years.
It is known that the initial state of the reproductive system has a significant impact on the course and outcome of pregnancy. Significant differences in the frequency of spontaneous pregnancy in women Interrupt the main group. Since spontaneous abortions, developing pregnancy, fetal death, ectopic pregnancy were significantly more frequent in patients of the main group (18% and 1.5%, respectively, P <0.001). Thus, every fifth patient, who gave birth to a child with cerebral palsy, was at high risk for the development of perinatal complications.
Revealed a high frequency of chronic infections, such as the kidney and urinary tract, chronic inflammatory diseases of uterus and cervix erosion in patients of the main group indicates an important role in the genesis of infection complications of gestation and perinatal lesions formation in the fetus.
Currently, among the causes of miscarriage infectious agents are leaders. Mostly this mixed infection and, in rare cases, a mono-infection. The greatest danger is the persistent infection, are asymptomatic when infection "nests" deep in the crypts of endometrial and intracellularly and is difficult to diagnose, which manifests itself mainly in the occurrence of pregnancy. Infection is transmitted primarily by the upward and hematogenic and transplacental. Activators can be varied:. Viruses, bacteria, streptococci and staphylococci, Klebsiella, Proteus, Mycoplasma, etc. The infection may lead to lesions of nondeveloping pregnancy (NP) with fetus and fetus formations (placenta membranes, umbilical cord, water), and without infection. NP Risk of infectious origin is particularly high in the presence of endogenous inflammatory lesions in the mother, genital and extragenital localization. The role of latent infection in women, especially in disorders of the immune relationship between mother and fetus. The infection can lead to the NP in the short terms, as well as to the formation of the CDF and other perinatal damage to the fetus.
Study of peculiarities of birth showed that the study group was significantly (21% and 5%) were more births were completed by cesarean section, while in 90.4% of cases of cesarean section performed on an emergency basis. The main indications for caesarean sections were abruptio placentae (33%), fetal threatening condition (19%), preeclampsia severe (19%), eclampsia (4.7%), at FFTS twins (4.7%) and also combines indications for operative delivery -primapara older and large fetus.
Obstetric aids and manipulation such as labor induction, birth-stimulation, episiotomy, vacuum extraction fetal applied only in 4% of patients of the main group.
Analyzing the features of a current delivery, it should be noted that the most frequent complication in patients of the main group were untimely amniorrhea 63 ± 2,1% vs. 24,5 ± 1,1% (p <0.001) cases in the control group.
Underlines high incidence of preterm birth in the primary study group (51% and 2%, respectively, P <0.001). These findings are consistent with the majority of domestic and foreign authors, which by one of the predisposing factors to the development of cerebral palsy include preterm labor. Prematurity has a large proportion of patients with a history of cerebral palsy and is, according to different authors, from 19 to 33.2%, while among all infants this figure is 4-8%. It is found that cerebral paralysis develops in premature infants, 8.7%, and its frequency is reduced in proportion to increase of gestational age and body mass. Cerebral palsy risk factors for the development of premature infants is associated with hypoxic injury, Qualification newborn status was based on inspection, Apgar scores, trends analysis early neonatal period of adaptation. Evaluation of the newborn Apgar estimated at 7-10 points recorded significantly more frequently in the control group. mild asphyxia significantly more often observed in children of the main group (18% and 2%, P <0.001). Heavy asphyxia at birth observed only among newborns main group (6%), whereas among the control group childbirth -absent.
Held on birthweight infants distribution analysis. Children weighing up to 1000 grams were 4%, from 1000 to 2000 g -30% by 2000 and up to 3000 g in 36.4% were born in the main group, while children weighing 3000.0 and above were significantly more marked in the control group (P <0,05). The following Table 1 shows some data of the statistical analysis of the results.

Findings
Thus, according to a retrospective analysis revealed the following features and complications in the perinatal period, which could promote the formation of cerebral palsy in children. Analytical results of the study are set fairly significant results in cerebral palsy development: • high frequency of urinary tract infections during the period of gestation were significantly more (P <0.001) is found in patients of the main group (36%), while this figure was 5.0 ± 2.1% in the control group; • gynecological diseases significantly (P <0.001) were more common in patients of the main group. Thus, chronic inflammation of the uterus and cervix erosion is more than 3 times encountered in patients of the main group (19%); • in the study history in patients of the main group was significantly (P <0.001) were observed more frequently prematurity (51%) and miscarriage (18%); • increase in the frequency of emergency caesarean sections (90%); • the most frequent complication in patients of the main group were delayed and prenatal amniorrhea 63%; • high frequency (48%) children at birth asphyxia varying severity. Asphyxia mild 24%, moderate severity 18% and 6% severe. The results of a retrospective study showed a significant role of adverse Pregravidal background, complications of pregnancy and childbirth in the implementation of the ICP. From this perspective, the problem of children born with cerebral palsy is relevant, there are many unresolved issues of both scientific and practical planning that require continued multilateral and in-depth research.

Discussion
Various sources report that premature children make a significant contribution to the number of children diagnosed with cerebral palsy (from 35 to 43%). [1,2,24] There is conflicting evidence from numerous studies: large analyzes of preterm births in some countries (mostly with high income) indicate that preterm birth rates have been increasing since the early 2000s. Blencowe et al. [25] reported that of 65 countries with reliable data on preterm births, 62 countries experienced an increase between 2000 and 2010. [26][27][28] At the same time, the rate of preterm births increased in most countries, but the magnitude of this increase was different. The increase in the multiple birth rate, as well as the frequency of preterm births with multiple pregnancies, contributed to an increase in the overall preterm birth rate. [29] In a series of works by Joshua P Vogel et al. (Switzerland, Thailand), which analyze the epidemiology of preterm birth, (from 22 weeks to 37 weeks) there are data reports that the growth of preterm birth is declining in developed countries. [30] In about half of the European countries (out of 19 included in the study), no changes occurred or the number of preterm births in single pregnancies decreased due to the development of preventive and diagnostic measures. [31] In Kazakhstan, the rate of preterm birth remains at the level of 6.4% [32][33][34] according to official data and reports of domestic authors, and according to the WHO it is 8.8 cases per 100 births. [35] Urinary tract infections, which are also one of the causes of cerebral palsy, also remain at the same level [33,34,36], they are also often the cause of premature birth, which in combination can give an increased risk of developing cerebral palsy in the fetus / child [26][27][28], especially noted pyelonephritis [29], which in our work reliably showed a connection in the development of cerebral palsy.
One of the limitations of this work was that we did not divide children by weight, since the previous authors had already specified that among newborns with a weight below 1500g. there is a decrease in the total number of cerebral palsy. [15,22,23] The same stable indicators are observed for all other categories that can cause the development of cerebral palsy [37], which raises additional questions regarding the increase in the incidence of cerebral palsy in Kazakhstan.
The limitation was the lack of a single database and scattered information across all maternity hospitals in Almaty, and the lack of an electronic database, which made it difficult to collect material for work. Further work is required to clarify the main reason for the growth of cerebral palsy in Kazakhstan and find ways to prevent them. Informed Consent Statement: Not applicable Data Availability Statement: The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions