Научная статья на тему 'Medical and biological assessment of the fluoride content of bottled water'

Medical and biological assessment of the fluoride content of bottled water Текст научной статьи по специальности «Фундаментальная медицина»

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Ключевые слова
BOTTLED WATER / TOXICOLOGY / FOOD SAFETY

Аннотация научной статьи по фундаментальной медицине, автор научной работы — Zokirkhonova Shahzoda

It has been established that the fluoride content of bottled water with concentration of 0.7-1.0 mg/L is not toxic, it does not cause irritation action to the skin and mucous membranes of the eyes, has no cumulation and sensitizing properties. Bottled water containing fluoride concentration of 0.7 and 1.0 mg/l, can be attributed to non-toxic and lowhazard products.

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Текст научной работы на тему «Medical and biological assessment of the fluoride content of bottled water»

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Fig. 1. Seasonal distribution of acute gastroenteritis among children under the age of 5 years, depending on the pathogen

References:

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12. Amaral M. S. et al. The prevalence of norovirus, astrovirus and adenovirus infections among hospitalised children with acute gastroenteritis in Porto Velho, state of Rondonia, western Brazilian Amazon//Mem Inst Oswaldo Cruz. - 2015.

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Zokirkhonova Shahzoda, Tashkent State Dental Institute, Researcher of the Department of hospital dental therapeutics E-mail: [email protected]

Medical and biological assessment of the fluoride content of bottled water

Abstact: It has been established that the fluoride content ofbottled water with concentration of 0.7-1.0 mg/L is not toxic,

it does not cause irritation action to the skin and mucous membranes of the eyes, has no cumulation and sensitizing properties.

Bottled water containing fluoride concentration of 0.7 and 1.0 mg/l, can be attributed to non-toxic and low- hazard products. Keywords: bottled water, toxicology, food safety.

Background

The biological role of fluoride in the body is determined by its ability to regulate the processes associated with tissue calcification. The normal content of fluoride in the body creates (mineralizes) the tooth bone, enamel and dentine [1]. Nearly the whole body fluoride (99 %) is localized in solid tissues [2]. Its higher concentration in the soft tissues such as in vascular walls indicates their pathological calcification. It has been found that about 75 % of alimentary fluoride comes from drinking water, beverages and liquid food [3]. The fluoride content in the drinking water of cold and moderate climate zones is normalized at the level of 1.2-1.5 mg/l, and in hot regions — 0.7 mg/l. [6]. When the fluoride content in drinking water is below 0.5 mg/l, it requires water fluorination to prevent the lack of fluoride conditions and, in the first place, tooth decay.

It is normally used the soluble compounds of the element: NaF and Na2 SiF6 for fluorinating r [6; 7]. In recent years, there is the practice of fluoride enrichment of salt (with iodine): 1 g. of salt contained 0.25 mg. of fluoride. Such salt can be effectively used in the regions where the primary source of drinking water has a low fluoride level and there is no practice of its fluorination [7]. At the same time, should be necessary to balance the fluoride body intake considering the real possibility of development of dental fluorosis — microel-ementosis that is associated with hyper fluorosis. Specialists of the National Academy of Sciences of the USA suggest that daily safe dose is from 1.5 to 4 mg. of fluoride [7; 8]. Excessive body intake of fluoride develops fluorosis, which is clinically expressed as erosive pigmentary tooth lesions and skeletal deformities.

The overwhelming majority of the population of the Republic of Uzbekistan lives in low and non-fluoridated areas and at high risk of developing tooth decay. In order to prevent the developing tooth decay it is necessary to carry out the artificial enrichment of organism with fluoride, the safer, convenient, effective way is water fluoridation of drinking water. Water that contains an adequate amount of fluoride helps prevent tooth decay and build strong teeth. As shown by recent studies, the high dental disease in the Republic of Uzbekistan presents the real threat to the health of younger generation. According to A. S. Yuldashkhanova et al. (2005), on the territory of the Republic, among preschool children who are living in the city, the prevalence of tooth decays has been 87.76 %, with the intensity of 3.96, and among preschool children who are living in the rural areas, the prevalence of tooth decay has been 80.91 % with an intensity of 3.3 [5]. Tashkent city tap water fluoride concentration is 0.36 mg/dm3 (very low fluoride concentration in water). In this regard, the development of fluoridated bottled water is very important.

We designed the bottled water enriched with fluoride in collaboration with technologists of Republican Association "Mon-tello" As an evaluation criterion for daily dose of fluoride intake of preschool age children they used "Conservative age-limits of daily fluoride intakes" worked out by T. M. Martaler (1992). According to these limits, the level of fluoride income in the organism of preschool children should be 0.8-1.75 mg. per day, which is justified by the high energy consumption of this age period. There used sodium fluoride to prepare bottled water.

The above has been the basis for toxicological studies of the fluoride content of bottled water in concentration of 1.0 mg/L — the study of systemic toxicity with the assessment of the possible irritant effect on the mucous membranes as well as its potential cumulative effects and allergenic activity.

Aim of the research

Toxicological evaluation of the fluoride content of bottled water in concentration of 1.0 mg/L after intragastric administration

of putative toxic dose to laboratory animals with further follow-up within the experiment to determine the clinical signs of intoxication.

Objects of research

The fluoride content of bottled water in concentrations 0.7 and 1.0 mg/L.

Materials and methods of research

Experimental studies were performed on 36 white mongrel male rats with body mass 130-160 g. and 36 pregnant females weighing 207-241 g. that were kept separately in vivarium Inter-university Research Laboratory (IRL) of the Tashkent Medical Academy on balanced diet for the content of proteins, fats and carbohydrates. All animals had been receiving bottled fluoridated water for 90 days [3; 4]. 36 male rats were divided into 3 groups. Group 1 animals were administered 3.0 ml. of 0.0001 % (fluoride concentration is 1.0 mg/l, equivalent dose 0.12-0.14 mg/kg) fluoridated water per 100 g. of body weight daily two times a day. Group 2 animals were administered 3.0 ml. of 0.00007 % (fluorine concentration is 0.7 mg/l, equivalent dose of 0.084-0.098 mg/kg) fluoridated water two times a day per 100 g. of body weight. Taking into account that the rats with 200 g. body mass consume on average 30-35 ml. of fluid per day, the rest of fluoridated water the animals took on their own from the drinkers. Group 3 was used as a control. The same way was distributed 36 female rats. Study of the acute toxicity of the fluoride content of bottled water concentrations of 0.7 and 1.0 m g/l (equivalent doses 0.084-0.098 and 0.12-0.14 mg/kg body weight, respectively) was performed on sexually mature white male rats with an initial weight of 130 -160 g. Three experimental groups included 6 animals in each group. Fluoridated water injected daily, morning and evening doubly per os at 3.0 mL. per 100 g. body mass. 20-25 ml. of fluoridated water was left in the open drinkers. After 3-4 hours after introduction of fluoridated water the animals were given organic and briquette food. The follow-up of experimental animals was being carried out for 90 days [3-4].On the expiry of 90 days 36 rat females after mating were divided into 3 groups. Pregnant females of 1 group daily 2 times a day were being injected 3.0 ml. 0.0001 % (equivalent dose 0.12-0.14 mg/kg) of fluoridated water per 100 g. of body weight. Group 2 animals daily two times a day were being administered 3.0 ml. of 0.00007 % (equivalent dose 0.084-0.098 mg/kg) of fluoridated water per 100 g. of body weight. Taking into account that the rats with 200 g. body mass consume on average 30-35 ml. of fluid per day, the rest of fluoridated water the animals took on their own from the drinkers.

Newborn rats on the 3rd, 7th, 10th and 14th day were carried out histomorphological studies of the thyroid gland and femur osteogenesis. Study model of osteogenesis of little rats' teeth was rejected due to the fact that rats could get fluoride from their mother's milk. In this case, the teeth in varying degrees expose residual quantities of fluoride in milk.

Clinical analyzes of rat blood was performed according to standard procedures [6; 7]. Biochemical indices of blood serum were determined with uniform methods: total protein — biuretic, albumin — bromo cresol, glucose — glucose oxidase, aspartate aminotransferase (ACAT) and alanine aminotransferase (ALT) — standardized methods by Reitman-Frankel, alkaline phosphatase — standardized method using nitrophenylphosphate (sets of chemicals of company CYPRESS Diagnostics, Belgium) [15]. Statistical analysis was conducted to determine the reliability of the criteria for laboratory research on methodical recommendations "Use of the principles of evidence-based medicine in organizing and conducting health studies" on the basis of the Word 2003.

The results of their own research

Observation of experimental animals was being carried out for 90 days. The symptoms of intoxication and death of animals was not recorded. The experimental animals remained active, neat, readily ate the food, wool was smooth, shiny, react to external stimuli adequately. In the absence of the death of experimental animals, and symptoms of intoxication, to calculate the mid-lethal dose (LD50) was not possible.

Thus, in the absence of toxic symptoms and death of the animals in acute trials the fluoride content of bottled water in concentration 0.7 and 1.0 mg/L by the parameters of toxicity degree can be related to class 4 — low-toxic substance.

The next step, we studied the local skin and skin- resorption effect of the fluoride content of bottled water. Studying of topical fluoride content of bottled water in concentrations 0.7 and 1.0 mg/L on the skin and mucous membrane of eyes as well as the ability to penetrate intact skin were conducted on white male rats. Fluoridated water was applied the skin of the experimental animals at the rate of 20 mg/cm 2. Skin reaction was recorded after 4-hour exposure after 1 and 16 hours after a single application. It was found that bottled water containing 0.7 and 1.0 mg/l of fluoride does not cause irritation of the skin.

It was studied the toxicity of multiple exposure to the skin of white rats treated with 20 cutaneous applications of fluoridated water. It is established that during the whole experiment period the death of the animals and clinical signs of toxicity was no observed.

To identify the skin-resorption effect white rats were fixed in special machines. Tails of experimental animals were dipped in the tubes with fluoridated water for 4 hours at 36-37 °C. After ending the experiment the skin tails were washed with soap and water. No death and signs of intoxication of experimental animals were observed within 3 week-follow-up.

Thus, the study results allow stating the lack of bottled water containing fluoride concentrations of 0.7 and 1.0 mg/l of local skin and skin-resorption effect.

The further step we studied the effect of bottled fluoridated water on mucous membrane of the eyes. In conjunctival sac of the right eye of rats was added one time 2 drops of bottled water containing fluoride concentration of 0.7 and 1.0 mg/l, the left eye was as control. No changes revealed of the water exposure to fluoride concentration of 0.7 mg/L. It was marked lacrimation under the influence of fluoride concentration of 1.0 mg/L after 2 minutes. After 3-3.5 minutes this phenomenon was completely disappeared. Consequently, the obtained findings showed that bottled fluoridated water under investigation in concentrations close to the technological use has no irritant effect on mucous membranes.

The ability to cumulation ofbottled fluoridated water was studied by Lima subchronic toxicity under repeated intragastric administration to white rats. It was used white male rats weighing 130-160 g. in the experiment. Bottled fluoridated water had been administered in-tragastrically 2 times a day within 4 weeks. Control animals received distilled water in equal volume. As indicators ofthe functional state of the animals they used: survival during the experiment, general state, animal activity, dynamics ofbody weight, morphological composition of peripheral blood, the content of total protein, albumin, glucose, ALT, AST, alkaline phosphatase activity.

No behavioral deviations and general condition in animals within the follow-up period were observed. No signs of toxicity and deaths were noted. The dynamics of body weight growth of white rats has been shown in Table 1.

As it is seen from the data presented in Table 1 the statistically significant delays of body weight growth no found.

Consequently, these results indicate the absence of the negative effect of fluorinated water on physiological growth in laboratory animals.

Table 1. - Dynamics white rats body weight at intragastrical multiple-dose introduction of bottled water with fluoride content of 0.7 and 1.0 mg/l within a month

Name of animal groups Doses mg/kg Statistics Animal weight, g. Amount of growth in %

Initial On the day of slaughter

Control - M ± m 137.0 ± 2.9 162.0 ± 1.6 182

Bottled fluoridated water (0.7 mg/l) 0.084 M ± m 143.7 ± 4.4 156.3 ± 5.0 6.1

0.098 M ± m 128.2 ± 2.5 155.3 ± 3.1 17.4

Bottled fluoridated water (1.0 mg/l) 0.12 M ± m 133.2 ± 1.4 155.0 ± 2.1 16.4

0.14 M ± m 135.7 ± 4.4 165.3 ± 5.0 21.8

In terms of chronic experience the toxicity of bottled fluoridated water was studied with the introduction of water to white rats per os 2 times a day within 90 days. The experiment was used white male rats weighing 130-160 g. Study of the dynamics of the content of hemoglobin, erythrocytes, leukocytes, eosinophils, lymphocytes, monocytes, platelets, and segmented, color index and ESR in the

peripheral blood revealed no revealed statistically significant differences in the treated group of animals compared with control data (Table 2-5). Analysis of study results revealed that the group of animals exposed to water with fluoride concentration of 1.0 mg/L, the values were similar to control parameters, whereas, the exposure of fluoride with concentration 0.7 mg/l was slightly below controls.

Table 2. - Hemoglobin, erythrocytes and leukocytes in peripheral blood of white rats after intragastric administration of bottled fluoridated water within a month

Name of animal groups Doses, mg/kg Statistics Hematological indices

Hemoglobin content, g/l Erythrocyte content, g/l Leukocyte content, g/l

Control - M ± m 136.3 ± 4.4 4.43 ± 0.13 4.93 ± 0.43

Bottled fluoridated water (0.7 mg/l) 0.084 M ± m 128.3 ± 2.3 4.7 ± 0.2 4.32 ± 0.31

0.098 M ± m 130.7 ± 2.4 3.80 ± 0.3 4.51 ± 0.62

Bottled fluoridated water (1.0 mg/l) 0.12 M ± m 137.3 ± 3.3 4.4 ± 0.13 4.77 ± 0.38

0.14 M ± m 135.7±4.4 4.38 ± 0.12 4.92 ± 0.45

Table 3. - Color index, platelets and segmented content in peripheral blood of white rats after intragastric administration of bottled fluorinated water within a month

Name of animal groups Doses? mg/kg Statistics Hematological indices

Color index Platelet content, 10 9/l Segmented, %

Control - M t m G.92 t G.G3 2?.? t 15.G 52.? t 3.?

Bottled fluoridated water (0.7 mg/l) G.GS4 M t m 076 t G.G4 255.S t 1G.S 507 t 2.2

G.G9S M t m 075 t G.G3 2б5.4 t 12.G 54.5 t З.б

Bottled fluoridated water (1.0 mg/l) G.12 M t m G.SS t G.G2 2657 t 11.2 52.5 t 3.2

G.14 M t m G.S5 t G.G2 2?5.б t 14.2 51.? t 4.б

Table 4. - Content of eosinophils, lymphocytes, monocytes and ESR in peripheral blood of white rats after intragastric administration of bottled fluorinated water within a month Hematological indices

Name of animal groups Doses, mg/kg Statistics stics Hematological indices

Eosinophils, % lymphocytes, % Monocytes, % ESR, mm/h

Control - M t m 1.1? t G.l? 3?.3 t 2.S 5.S t G.6 5.S t G.9

Bottled fluoridated water (0.7 mg/l) GGS4 M t m 1.33 t G.21 41.2 t 4.G б.5 t G.S 5.? t 1.2

G.G9S M t m 1.1? t G.22 36.S t 3.5 б.З t 1.1 б.З t G.?

Bottled fluoridated water (1.0 mg/l) G.12 M t m 1.21 t G.3 3?.S t 4.G 5.9 t G.4 5.9 t G.1G

G.14 M t m 1.2б t G.43 Зб.б t 1.5 б.2 t G.9 б.5 t 1.5

Table 5. - Biochemical indices of white rats after 90 day-intragastric administration of bottled fluoridated water

Groups Doses, mg/kg Total protein, g/l Albumin, g/l Glucose, U/l ALT, U/l AST, U/l Alkaline phosphatase, U/l

Intact - 73.41 ± 2.29 42.GS t G.S6 571 t g.6? 2?.33 t 6.26 26.66 t 5.33 33.01 ± 4.02

Bottled fluoridated water (0.7 mg/l) G.GS4 72.94 ± 0.82 44.2 t l.G 5.S t G.9 26.4 t 3.G3 2S.S t 2.45 33.6 ± 2.1

G.G9S 70.4 ± 1.5 46.G t 1.9 5.5 t G.9 25.S t 2.6 29.5 t 2.S 35.6 ± 2.30

Bottled fluoridated water (1.0 mg/l) G.12 72.94 ± 2.77 41.13 t 1.33 5.15 t G.5S 26.5S t 5.6S 2S.25 t 5.SG 34.86 ± 4.00

G.14 74.36 ± 1.22 43.43 t G.9S 5.6S t G.6S 24.S3 t 4.9? 30.06 t 5.06 37.16 ± 3.76

Thus, values of hemoglobin, erythrocytes, leukocytes, eo-sinophils, lymphocytes, monocytes, platelets, and segmented, color index and ESR in the peripheral blood of animals are closer to the control digits, which suggest that the fluoride concentration of 1.0 mg/l is optimal.

Study results of some biochemical parameters of blood serum (total protein, albumin, glucose, ALT, AST, alkaline phosphatase) of experimental and control animals are shown in Table 6. Analysis of the data showed that the values of total protein indicators, albumin, glucose, transaminase enzymes (ALT, AST) and alkaline phosphatase activity in blood of experimental animals were not significantly different from control values.

Thus, the study results of biochemical blood indices in experimental animals exposed to bottled water in fluoride doses 0.084, 0.098, 0.12 and 0.14 mg/kg animal weight are fluctuated within physiological norms and do not differ from the controls.

When choosing the optimal concentration of fluoride in bottled water it is also need to be considered climatic conditions, i. e., to follow seasonal principle of water fluoridation. For summer time

when the temperature is above 26.2 °C - 30 °C, it is preferably to give children the bottled water with concentration of 0.7 ± 0.1 mg/L, and for autumn and winter time — with fluoride concentration of 1.0 ± 0.1 mg/L due to reduced water consumption by children this time. Along with this, it is necessary to take into account the number of consumed milk, vegetables and other dietary habits.

Thus, the use of bottled fluoridated water with optimal selected fluoride concentration of 0.7 and 1.0 mg/L depending on the season allows for the most effective prevention of tooth decay and osteoporosis, both at the individual and social levels.

Conclusions:

1. Bottled water containing fluoride concentrations of 0.7 and 1.0 mg/L is to be non-toxic, does not cause irritant action to the skin and mucous membranes of the eyes, has no cumulation and sensitizing properties.

2. Bottled water containing fluoride concentrations of 0.7 and 1.0 mg/L can be attributed to non-toxic (relatively harmless by S. D. Zaugolnikov) and low-hazard (1V) class of hazard (G0ST12,1.007) for foods.

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2. Lukinykh L. M. Evaluation of tooth decay in children aged 3-6 years in different regions of Nijniy Novgorod with low dentistry. -2001. - № 4. - Р. 73.

3. MUK (Guideline) 721-98 2.3.2 "Food and nutritional supplements. Determination of the safety and efficacy of dietary supplements in the diet". - Moscow, 1999.

4. OECD standards on chemical investigations number 423 "Accurate toxicological evaluation - the classic method". - March 22, 1996.

5. Khalilov I. H., Yuldashkhanova O. S., Rakhmonov Kh. Sh. Children therapeutic stomatology and dental diseases. - Yangiyul, 2006. -Р. 35-38.

6. Richard K. Yoon, Arlene M. Smaldone, Burton L. Edelstein. Early childhood caries screening tools. A comparison of four approaches// The Journal of the American Dental Association. - 2012. - № 06. - P. 756-763.

The influence of active inflammation on parameters of central hemodynamics in pregnant women...

7. Dye Bruce A., Shenkin Johnathan D., Ogden Cynthia L., Marshall Teresa A., Levy Steve M., Kannellis Michael J. The relationship between healthful eating practices and dental caries in children aged 2-5 years in the United States, 1988-1994//J. of the Am. Dental Ass.

8. Davenport E. S., Litenas C., Barbayiannis P., Williams C. E. S. The effects of diet, breast-feeding and weaning on caries risk for pre-term and low birth weight children//Int. J. Paediatr. Dent. - 2004. - Vol. 14(4). - P. 251-259.

Zakirova Feruza Akildjanovna, Candidate of Medical Sciences, Doctoral Student of the Republican Specialized Center of Cardiology E-mail: [email protected] Bekbulatova Indira Rinatovna, Candidate of Medical Sciences, Scientific Secretary of the Republican Specialized Center of Cardiology E-mail: [email protected] Eliseeva Marietta Rafaelevna, Doctor of Medical Sciences, Professor, Chief Editor of the magazine «International Journal of Biomedicine»

E-mail: [email protected]

The influence of active inflammation on parameters of central hemodynamics in pregnant women with rheumatic heart defects

Abstract: The functional state of the cardiovascular system in women with rheumatic heart defect in conjunction with the activity of rheumatic process has been studied thoroughly. The results have revealed a higher frequency of heart contractions, the prevalence of ectopic activity in pregnant women with active rheumatic process. The activity and effectiveness of rheumatic process has also caused the slowing of the pulse conducts in myocardium of atria and ventricles, increasing of both linear and volumetric parameters of heart.

Keywords: pregnancy, rheumatic heart defects, rheumatic process activity, functional state of the cardiovascular system.

The cardiovascular system defects (CSD) in pregnant women continue to occupy the leading position within the structure of extra genital pathology and appear to be an important issuedue totheir prevalence, as well as the influence on maternal and perinatal mortality. During manydecades the rheumatic defects were frequent extra genital pathology in pregnant women [7]. But in recent decades, the incidence of the above mentioned defectin pregnant womenhas been declined due to the successful prevention of rheumatic fever [4]. It was established that 0.1-0.3 % of people, predominantly youth age, and women more often than men, are suffering from rheumatism. Moreover, 90 % of acquired heart defects have rheumatic etiology. Theheart disordersare referred to the group ofhigh risk cardiovascular complications and make up 5-10 % of all cardiovascular defects (CVD) [3]. There has been recently observed an increase in the number of pregnant women and mothers suffering from heart defects, which is explained bya number ofreasons: the early diagnosis of such defects; the possibility ofpregnancy maintenance in cases which were previously impossible; an increase in the number of women who have had a heart surgery, and the number of seriously ill women who are either by doctors'permission, or independently themselves decide to continue the pregnancy, being confident in the success of medical science and practice. The exacerbation of rheumatoid process affects the fetal developmentadversely, increases the risk of developing of complications from mother's side during pregnancy, as well as childbirth and postpartum period. This is explained by the fact that pregnancy increases the load on cardiovascular system, even in healthy women, while at risk of hemodynamic changes due to existing defects, the load increase many times многократно [5]. Fetal hypoxia, fetal death, malnutrition, prematurity, neonatal asphyxia, malformationsare common cases [6].

Objective: The identification of the influence of an active inflammatory process on parameters of central hemodynamics in pregnant women with rheumatic heart defect.

Research methods and materials

The study involved 70 pregnant women with rheumatic heart defectat the age of 19-35 years, in 2 and 3 trimester of gestation. Along with collecting the complaints and anamnesis data, the physical examination was also conducted during pregnancy. The evaluation of the functional state of the cardiovascular system was carried out comprehensively, taking into account the electrocardiographic and hemodynamic parameters. The electrocardiographic (ECG) indicators included: ECG in 12 standard leads. The assessment of hemodynamic parameters includedthe analysis of heart rate (HR); the level of blood pressure (BP), measured due to the standard method of Korotkov. For studying the intracardiac hemodynamics, the echocardiography method was appliedby device "SONOLINE VERZA PRO" («Siemens», Germany), in accordance with the recommendations of the American Association ofEchocardiography in M and B modes (Sahn D. J. et al. 198.) The image was obtained using the M-method, which allows to record the movement of reflective surfaces and provides an opportunity to measure the distance changing over the time. The measurements in M-mode were carried out via the parasternal access along the axis of the left ventricle in accordance with the recommendations of the Penn Convention Method.

The laboratory blood tests included complete blood count (CBC), the revmo sample definition (RS) and prothrombin index. According to the results of the CBC and the RS, the surveyed patients were divided into 2 groups: 1stgroup — 50 pregnant women (71.4 %) with the presence of active rheumatic process; 2ndgroup — 20 pregnant women (28.6 %) without activity of rheumatic process.

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