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Kamalidinova Shakhnoza Mahmudkhanovna, Tashkent Institute for Advanced Medical Education,
Tashkent, Uzbekistan E-mail: [email protected]
DOWN SYNDROME AND MATERNAL AGE
Abstract: Our statistical analysis once again proves the absence of an age factor as a risk of having children with Down syndrome, and an increase in the birth of children with Down syndrome in mothers aged 19 to 35 is directly related to the increase in the number of births.
Keywords: Down syndrome, maternal age factor.
Aneuploidy are the main causes of perinatal mortality, among which Down syndrome is one of the most frequently occurring forms of chromosomal abnormalities [1; 2]. Every year, the number of births of children with Down syndrome grows on average by 0.9% of cases per year, compared with the previous year. The frequency of birth of children with Down syndrome averages 1: 800 [2]. Most authors in 70% of cases associate the risk the birth of children with trisomy 21 maternal age and 30% with the age of the father [3; 4]. So when a mother is under 30, the probability of having a child with Down syndrome is 1: 2500, at 31-34 the risk of birth increases and is 1: 1200, the greatest risk of birth occurs at 35-39 years -1: 200 [2; 7, 8].
However, the data given by the authors indicate that the development of a risk scale for the birth of children with Down syndrome was compiled in relation to the children already born with trisomy 21 to the total number of newborns [7; 8]. In drawing up the risk of having children with Down syndrome, the number of miscarriages, abortions and fetal death, the risk of which in trisomy 21, starting at 12 weeks of gestation, is about 30% was not taken into account. For comparison, the risk of fetal death of an euploid fetus is only 1-2% [1]. In the early 1970s, the number of pregnant women over 35 years old was only 5%, among which 30% of the total number of fruits was with trisomy 21. In subsequent years, there was a general tendency in pregnant countries to become pregnant at an older age, the number of pregnant women over 35 years old increased. up to 20%, and therefore the number of fruits with trisomy 21 [1; 5] increases.
In contrast to developed countries, in developing countries, the peak birth rate is between 22-26 years old and women's birth rate is 35 years old and an average of 80% compared to women over 35 years old - 20%. The number of registered fruits with trisomy 21 in women under 35 years old is 4 times higher compared with older women [10-12].
It should also be noted that all complete trisomies occur only on autosomals rich in heterochromatin, which are located on chromosome 8, 9, 13, 18 and 21, in most cases
(90%) trisomy occur due to non-divergence of chromosomes in meiosis. It can be assumed that the incidence of trisomy on chromosomes (8, 9, 13, 18, and 21) will occur in all cases the same. Although trisomy 18 and 13 chromosomes are relatively rare (1: 7000-1: 14000), but the dependence on the woman's age is less severe compared to trisomy of chromosome 21 [12]. For comparison, the risk of having a child with Edwards syndrome, for women over 45, is only 0.7% compared with Down syndrome over the age of 45, the probability of which is 3-5% [10-12]. The absence of the age factor is indicated by Ferguson-Smith (1983) data, which showed that the risk of having children with Down syndrome aged 35 and 39-47 years is higher compared with women older than 47 years. Mattei J. F. etall also revealed the absence of age as a factor in non-divergence of chromosomes in meiosis. The failure of the age-risk theory also indicates the low sensitivity of the method for diagnosing Down syndrome according to age risk [9]. In this analysis, we decided to study the effectiveness of prenatal diagnosis without taking into account the age risk of the mother, as well as having a relationship between the parents' age.
The purpose of this study is to assess the effects of various demographic factors on the prevalence of newborns with Down syndrome and to study the patterns of the influence of these factors in different populations.
Materials and research methods. This study is the result of a study of the demographic indicators of Uzbekistan, as well as some cities in Western Africa, North and South America, Eastern and Western Europe, Southeast Asia and South Asia. Individual records of birth and Down syndrome were collected as a result of the use of a program for the diagnosis of congenital and hereditary diseases conducted at the Republican Screening Center for Mother and Child from January 1, 2008 to December 31, 2011.
Consent to this study was obtained from the administration of the Republican "Screening Center for Mother and Child", as well as from pregnant women who agreed to undergo prenatal diagnosis.
DOWN SYNDROME AND MATERNAL AGE
As a result of the study, we retrospectively analyzed 516, 448 questionnaires of female-bearing children without a genetic pathology, 514 questionnaires of children with Down syndrome. Separation by ethnic groups was not carried out, as these data are not available in the questionnaires of pregnant women. Maternal and paternal ages were studied as continuous and categorical variables. The age was divided into 7 groups as categories divided by a five-year interval (up to 19 years, 20-24, 25-29, 30-34, 35-39, 40-44 and over 45 years), and two age categories up to 35 and over 35 years old. We used seven and two age categories to identify possible non-linear trends in the relationship between the age of the parents, the prevalence of Down syndrome and the number of births.
Biochemical screening was performed to calculate the risk of having a child with Down syndrome using test systems on the "DELFIA" apparatus - A067-101. Blood sampling was carried out according to generally accepted standards on an empty stomach from the brachial vein in the elbow joint. The biochemical parameters of AFP, hCG were studied.
The results of the study. According to the results of the studies conducted from 2008 to 2011, among the 516448 pregnant birthless children without genetic pathology, the largest number of births was between 20 and 24 years old and averaged 38.8%. The average age of pregnant women who gave birth to children without genetic pathology was 26 years. The prevalence of children with Down syndrome in the Republic of Uzbekistan from 2008 to 2011 ranged from 0.51 to 0.79 cases per 1000 newborns. On average, the number of children born with Down syndrome is 0.62 cases per 1000 newborns or the birth of one child with Down syndrome per 620 people. Compared to the Czech Republic, the prevalence of children with Down syndrome is 1 case per 530 live births, the birth rate of the state of California was 1 case per 1150 babies. In the study of fertility among women who have given birth to children with Down syndrome, the largest number of births from 2008 to 2010 falls on the age of 20 to 24 years, in 2011 the largest number of births ranged from 25 to 29 years. The average age of pregnant and giving birth to children with Down syndrome was 30 years. The largest number of children with Down syndrome were registered among fathers aged 25 to 29 years old, the average number ofwhich was 21.4%. The average paternal age was 33 years. Such a clear distinction between maternal and paternal ages is due primarily to the fact that most of the number of unions are between couples with a difference of three years, this is confirmed by the strong correlation dependence of 0.86 between the mother and paternal ages. The largest percentage ofbirths in women without genetic pathology is in the age range from 16 to 34 years (90.02%), women over 35 give birth to only 9.98%. Among them, the highest percentage of births of children with Down syndrome
occurs at the age of up to 35 years, women from 35 years and older give birth - 30.86%. There are 0.52 children with Down syndrome per thousand pregnant women up to 35 years old, compared with women over 35 years old - 2.1. Whereas the average age of women and father is 33 years. The prevalence of birth of children with Down syndrome in all age groups in the Republic of Uzbekistan from 2008 to 2011 ranged from 0.51 to 0.79 cases per 1000 newborns. On average, the birth of a child with Down syndrome is 1 case per 625 newborns without a genetic pathology.
During the study, we formed 3 groups of pregnant women. The first group included 512658 women with a physiological course of pregnancy without age risk. The second group consisted of3383 women with a high age risk of having children with Down syndrome by the physiological course of pregnancy. In the third group of 514 children with Down syndrome. The number of examined pregnant women from 14 to 20 weeks of pregnancy averaged 73720.14. The average age of pregnant women did not change from the year of the study and the period of gestation, which was 24 years. The number of women who gave birth to children under 16 to 35 years old is 23365 (87.35%), pregnant women 35 years old and over 3383 (12.65%).
The number of women giving birth to children with Down syndrome from 16 to 35 years old is 400 (77.82%), 35 years old and over 114 (22.18%). The distribution of children born without genetic pathology and children with Down syndrome between the ages of 19 and 30 years old shows a relatively high birth rate among children without genetic pathology - 58.11% and in children with Down syndrome - 22.71% compared to the birth rate from 31 to 40 years old, the number of children without genetic pathology was 12.7%, and the number of children with Down syndrome was 3.69%, which is approximately 3.2 times less than women who gave birth between the ages of 19 and 30.
Distribution of children born without genetic pathology and children with Down syndrome between the ages of19 and 34 years, the birth rate is higher among both children without genetic pathology - 72.12% and in children with Down syndrome - 8.7% compared with birth rates from 35 to 40 years old, the number of children without genetic pathology was 15.49%, and the number of children with Down syndrome was 3.69%, which is about 2.4 times less than women who gave birth between the ages of 19 and 34. For a comparative analysis, all women, depending on age, were divided into 4 groups, the first group included women from 19 to 24 years old, the second - 25-29 years old, the third from 30 to 34 years old and the fourth from 35 to 40 years old.
Conclusions and practical recommendations. Our statistical analysis once again proves the absence of an age
factor as a risk of having children with Down syndrome, and groups, thereby reducing the percentage of false-negative and
an increase in the birth of children with Down syndrome in false-positive results of this syndrome in women from 19 to 34
mothers aged 19 to 35 is directly related to the increase in the years. From this it follows that in the future it is necessary to
number of births. The exclusion of the mother's age as one of look for other etiological factors affecting the onset of Down
the main factors will equalize the chances when making high- syndrome, which will allow to reasonably form a group at high
risk groups of having children with Down syndrome in all age risk of having children with Down syndrome.
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