DEPENDENCE OF THE PERIODONTAL STATE OF INDIVIDUALS WHO WERE BORN MACROSOMIC ON THEIR HEIGHT-WEIGHT INDEX AT BIRTH

. The problem of long-term consequences of fetal macrosomia (birth weight greater than or equal to 4 kg), among which there are dental disorders, is urgent. Objective. To identify the features of the periodontal state of individuals in the City of Kharkiv and adjasсent area (Ukraine) population, born with macrosomia according to their weight-height index at birth. The identification takes into account intrauterine obesity, or intrauterine well-balanced development, or pre-natally formed relative body weight insufficiency. A separate objective of this study is to determine qualitative and radio-morpho-metric indices as markers of the bone mineral density of the jaws in the individuals in the City of Kharkiv and adjasсent area population, born macrosomic. Material and methods. During 2014–2019, two hundred and nineteen persons with different dental health conditions have been examined using clinical and radiological methods. One hundred and forty individuals between the ages of 11 and 55, who were born with macrosomia, constituted the Main Group, and seventy nine individuals of the same age, whose birth-weight parameters were normal (fetal normosomia), were assigned to the Comparison Group. Considering the

Introduction. The high prevalence of periodontal diseases even in children, adolescents and young adults necessitates paying attention to the early diagnosis of dental disorders. [1][2][3][4] The connection of obesity, accompanied by impaired microcirculatory processes and the immune response and, as a consequence, to the appearance of inflammatory-dystrophic diseases of periodontal tissues in 25-55-year-old persons, has been considered in [5][6][7]. The carbohydrate and lipid metabolism disorders in the case of obesity, complicated by metabolic syndrome, in 26-50-year-old persons were examined by scientists in Ukraine [8], who came to the conclusion that a decrease in the indicators of non-specific immunity and in antioxidant protection in the oral fluid in Original research such persons causes severe periodontitis. The pathological influence of alimentary-constitutional obesity on the clinical course of periodontal diseases and on the severity of the inflammatory process in 16-18-year-old adolescents was investigated by O. I. Lebid and K. M. Duda [9].
Metabolic osteopathies are the cause of bone disorders. It is known that intrauterine patterns and metabolic disorders, which occur intrauterinally affect all systems and organs of the newborn and are a prerequisite for the formation of many diseases and pathological conditions in ontogeny [10,11].
The significantly higher percentage of dentofacial anomalies in individuals born with macrosomia [12] (birth weight equal to or greater than 4 kg) causes the pathological changes to be identified. Today, a number of researchers [13] have proven that macrosomic newborns have a significantly reduced bone mineral density. The researchers explain this state of affairs by the reduced motion activity of the fetus due to its too large intrauterine size and point to a certain decrease in the bone mineral density with an increase in the body weight of the newborn [14]. However, we have not found the markers indicating the bone mineral density of the jaws in adults born macrosomic in the available literature. Such information could explain a large number of malocclusions in individuals whose birthweight parameters were higher than normal.
Therefore, if the macrosomic-at-birth person at the time of the examination is obese or underweight, usually none of the physicians is interested in the birth weight or draws parallels between the general condition at birth and the condition of the oral tissues at the time of the examination. However, the study of such relationships may shed light on some links in the pathogenesis of dental disorders. The information on the effect of intrauterine large body weight on bone density and the occurrence of periodontal diseases in later life is extremely scarce and difficult to obtain and analyze, so we consider it appropriate to investigate this problem.
The purpose of the study is to identify the features of the periodontal state of persons born with macrosomia from their height-weight index at birth. The identification takes into account intrauterine obesity, or intrauterine wellbalanced development, or pre-natally formed relative body weight insufficiency.
A separate objective of this study is to determine qualitative and radio-morphometric indices as markers of the bone mineral density of the jaws in individuals of the Kharkiv population and surrounding areas, born macrosomic.
Matearial and Methods. The study has been conducted at the Kharkiv National Medical University University Dental Center during 2014-2019. Clinical and radiological methods were used to examine 219 persons with different dental health conditions. One hundred and forty individuals between the ages of 11 and 55 who were born with macrosomia constituted the Main Group, and seventy nine individuals of the corresponding age, whose birth-weight parameters were normal (fetal normosomia), were assigned to the Comparison Group. The study did not include indi-viduals with obesity or diseases that affect the condition of tissues and organs of the oral cavity. The information on the weight-height parameters at birth of the participants in the study was obtained from the delivery records at the maternity hospitals, the inpatient medical records, the child medical history sheets, the newborn identification bracelet tags and from other medical records stored in the archives of the medical institutions or retained by the participants taking part in the study.
Based on the intrauterine harmonious coefficient, сoefficient takes into account the weight-height parameters of the newborn at birth, all participants in the Main Group were divided into four subgroups.
Subgroup I includes long and well-balancely developed at the time of birth individuals. Subgroup II includes persons who, at birth, had a long body length and relatively low body weight. Subgroup III includes persons who, at birth, were of long length and great body weight. Grishchenko VI. and co-authors classified such infants as intrauterinenally accelerated infants with obesity in the background. Subgroup IV includes persons who had an average body length and distincted overweight at birth.
The WHO classification is used as a basis for dividing the study participants by age, but the age period (AP), which coincides with the period of the permanent dentition development, is divided into two additional periods to account for changes in the oral cavity that are common for children in puberty.
The first AP included 11-17-year-old children who at the time of the study had all permanent teeth, with the exception of the third molars. The second AP included 18-24-year-old participants in the study. The 25-44-year-old participants with a completely formed permanent dentition were assigned to the third AP (according to the WHO classification, this age is young). The 45-55-year-old participants were included in the fourth AP. The distribution of the number of participants by groups and subgroups and somatometric indices of participants in the study at the time of birth is shown in Table 1.
The study has been conducted in accordance with the Council of Europe Convention on the Protection of Human To participate in the study, each participant over the age of 18 has provided informed consent. For participants under the age of 18, the informed consent has been obtained from the parents or guardians.
During the examination of periodontal tissue, the shape, color and the condition of the gum margin, have been taken into account, as well as the presence of edema, bleeding, and clinical attachment loss. The OHI-S (Green -Vermillion, 1969) has been used to determine the hygienic condition of the oral cavity. The determination of inflammation in periodontal tissues has been performed using the papillary-marginal-alveolar (PMA) index modified by Parma (1960); the determination of the gum recession

Table 1 Age distribution and values of mathematical expectation of weight-height parameters at birth of persons involved in the study
according to Miller (1985); and bleeding according to Sulcus Bleeding Index, Mühlemann-Cowell, (1975). To prevent confusion, the degree of destruction of the tooth supporting structures has been determined not by the depth of the periodontal pocket, but by loss of connective tissue attachment in dentogingival junction with the help of the periodontal probe in accordance with the technique described in [15]. The pathological changes in periodontal tissues have been recorded using the periodontal disease classification (M. F. Danilevsky, 1994). The panoramic radiographs (PR) of the participants in the study were assessed qualitatively in accordance with the technique described in [16].
The following three X-ray morphometric indices have been used to indirectly determine the optical density of bone tissue. The mental index (MI) (A. Taguchi, 1995) or cortical width of the mandible, which was measured on a line perpendicular to the lower part of the mandible in the middle of the mental foramen [17]; The Panoramic Mandibular Index (PMI) (B. W. Benson, 1991) was calculated as the ratio of the cortical layer of the mandible (MI) to the distance between the middle of the mental foramen and the lower margin of the mandible (L) [17]; the PMI index was chosen because it can be used to calculate the optical density of panoramic images taken with different equipment [17]. The panoramic radiographs (PR) has been obtained with the help of Soredex CRANEX D, NewTom Giano HR or Vatech co. ltd Pax-Uni 3D cone-beam computers. The length measurements have been performed with the E23D 2009 Viewer.
The optical density of the cortical bone has been measured under the mental foramen at the edge of the mandible, and the optical density of the trabecular bone tissue in the projection area of root apexes 45 and 46 with the Easy Dent 3D Viewer program. The tomographic studies have been conducted with the NewTom Giano HR and Vatech co. ltd Pax-Uni 3D cone-beam computers. The thickness of the cortical layer along the edge of the mandible (MIct) and the distance between the middle of the mental foramen and the lower margin of the mandible (Lct) have also been measured.
The mean values of the parameters under study were estimated by using MS Excel 2016 application. The smallgroup mean difference hypotheses were tested using the nonparametric statistics (Mann-Whitney criterion) applying Statistica 13 software. The percentage of cases in the observations of certain features in groups and subgroups with corresponding confidence intervals with a probability of error p < 0.05 was estimated for the binomial distribution of a random variable.
Results of the Study and Their Discussion. The state of oral hygiene (Table 2) among the groups does not differ significantly, and among the subgroups, but in Subgroups III and IV tend to the more better hygienic conditions.
In the first AP, the dental examination has revealed that 24 (92.3% CI: 80.4% -97.6%) adolescents in the Main Group were diagnosed with periodontal diseases; gingivitis was detected in 22 (85%) adolescents, and generalized periodontitis of the initial degree was found in 2 (8%) idividuals under examination from Subgroups I and II, and the healthy periodontium was revealed in two individuals from Subgroups III and IV. In the Comparison Group, gingivitis was detected in 12 (85.7% CI: 66.1% -95.3%) individuals.
High values of the PMA index in children with obesity, as compared to children with normal body weight, were found in the study by Kostura V. L. [18]. In our study, the children in Subgroups I and II (with well-balanced pre-natal development and relative insufficiency of body weight) were found to have the higher PMA index on average, but in the presence of pre-natal obesity, the index was at the level of that in the Comparison group.
The high values of the indices presented in Table  2 for the children in the Main Group and the Comparison Group in this AP are associated with pubertal changes and indicate that preventive measures are needed.
In the second AP, periodontal tissue diseases were found in 37 (94.9% CI: 86.5% -98.4%) persons ( Table 2). The data on the high prevalence of periodontal diseases in this AP coincide with the data in [3,19].
Pathological conditions of periodontal tissues include gingivitis (30% of individuals), generalized periodontitis of initial stage (35% of individuals), and gum recession with atrophy of the alveolar process (initial stage of periodontosis, according to the M. F. Danilevsky, (1994) classification) in 35% of the Main Group. The cases of periodontosis («low-inflammatory» destruction of the alveolar process) occurred only in persons who had intrauterine overweight (subgroups III and IV). Eleven of 21 individuals, the total number of individuals in the III and IV subgroups in this AP, exhibited gum recessions. In the Comparison Group, periodontal pathology was detected in 24 (85.7% CI: 71.8% -93.9%) individuals, 50% of whom had gingivitis, and in the 50% had periodontitis of initial stage.
Among the participants of the third AP, which were assigned to the Main Group, diseases of periodontal tissues were registered in 47 (94.0% CI: 86.3% -97.8%) individuals (Table 2). Fifty five percent of them, had a prevalence of inflammatory component: in 7 (15%) gingivitis 19 (40%) periodontitis; and 21 (45%) had a predominance of destructive component: atrophic processes, recessions accompanied by wedge-shaped defects. Only processes with prevalence of inflammatory component were recorded in subgroups I and II (Fig. 1). In Subgroups III and IV, total number of individuals 31, destructive processes with the «low-inflammatory» component was detected in 21 individuals (Fig. 2). In the Comparison Group, 25 (96.2% CI: 86.8% -99.1%) individuals had periodontal tissue pathology, 7 (28%) gingivitis and 15 (60%) periodontitis. Three individual (12%) had the «low-inflammatory» destruction of periodontal tissues. It should be noted that two of them were born with a body weight of 3.8 kg, which today does not correspond to the fetal macrosomia, but is still a sufficiently large body weight for the newborn baby.
The persons in the Main Group in the fourth AP had periodontal tissue disease in 100% of cases ( Table 2). All persons of Subgroups I and II had prevalence of inflammatory changes in the periodontium (Fig. 1), which were accompanied by hemorrhage and gum edema, and the presence of periodontal pockets. In subgroups III and IV, thirteen individuals out of 18, total number of persons of subgroups III and IV, sufferred from the periodontosis («low-inflammatory destruction»), which was accompanied by atrophy of the alveolar process, gum recession, rated as grade 1 or 2 (Fig. 2). The presence of wedge-shaped defects was detected. In the Comparison Group, eleven individuals (91.7% CI: 73.5% -97.9%) had pathological processes occurring in the periodontium: one (9%) had gingivitis, eight (73%) had 1-3 degree of generalized periodontitis, and two (18%) of the patients had periodontosis.
Anaysis of panoramic radiographs (PR). In order to confirm the above results, the PR of the participants in the study were selectively evaluated qualitatively and quantitatively. The number of evaluated panoramic radiographs and the averaged index values is shown in Table 3. The PR with defects was not evaluated, namely, the PR where the mental foramen was not visible, the PR of persons undergoing orthodontic treatment, or those with a history of trauma, or other diseases.
The group of specialists in the Department of Therapeutic Dentistry has analised the PR trabecular pattern. They divided all PR under investigation into 3 parts, the first part includes images with sparse trabecular patterns and uneven (vertical) bone resorption, the second part includes images with lighter tone, with dense trabecular patterns and even (horizontal) bone resorption, and the third part includes images with alternating dense and sparse trabeculation. It is known that the dense image of the trabecular bone with small intertrabecular spaces corresponds to the high bone mineral density, while the sparse pattern indicates a low mineral density [20]. It is also known that in presence of thin fenotype of gingiva horizontal resorption and gingival ressetion will occur [21]. And in case of thick gingival fenotype a vertical bony defect with periodontal pocket formation will take place.
The results of the image visual sorting completely confirmed the data obtained in the clinical study and revealed that the persons in Subgroups I and II had the radiological signs of mostly inflammatory destruction (periodontitis), and the persons in Subgroups III and IV had prevailing    The investigation of the panoramic radiographs for AP I persons drew attention to the anomalous arrangement of the dermis of the third molars. We have detected the retained third molars (RTMs) in the Main Group even in AP 4. But since for all 44-55 year-old persons, the past histories are difficult to collect (in relation to third molars), and during the AP I the formation of these teeth is not yet completed [22], the number of persons with RTMs in the lower and upper jaws is calculated only for AP III. It is known that the formation of jaw tissues is completed by 25-year age, but given the information, obtained by other scientists, that 80% of people have third molar roots formed [22] at the age of 20-21, and the fact that the mean age of individuals examined in AP II was 22 years, we have decided to examine this age. Table 3  A significantly higher percentage of persons in the Main Group who had RTMs (Fig. 3-5) with impaired eruption axis is both a sign of lack of space in the dentition [23] and confirmation of our earlier assumption [12] that the mandible was underdeveloped in persons whose birth parameters were higher the norm. From the bibliography, the percentage of retention of third molars is very different. The Russian scientists have found RTMs in 25% of the individuals examined, while the European scientists indicate that RTMs have up to 75% of individuals [22,24].

Table 2 Index assesment of the hygienic state of the oral cavity in Main and Comparison Groups: OHI-S index (Green-Vermillion, 1969), Sulcus Bleeding Index, (Mühlemann-Cowell, 1975), Papillary-Marginal-Alveolar (PMA) index modified by Parma (1960) and the level of clinical attachment loss in persons involved in the study
The percentage of persons with RTMs in the upper jaws was also calculated using the number of persons who had third molars formed. It was not significantly different among the groups and subgroups, accounting for 29.3% in  However, in some participants from AP II and AP III in the Main Group, retentions with unusual deviations of the axis of eruption of the teeth (Fig.  1) were found, which may also indicate insufficient space in the dentition.
Due to the fact that the PR visual examination has drawn attention to the disproportionately great thickness of the mandible cortical layer in the many participants in the Main Group (Fig. 4), the cortical layer was measured on PR. In AP II (18)(19)(20)(21)(22)(23)(24) year-old persons) all PR were performed on the same tomograph and by the same X-ray laboratory assistant, so it is possible to compare not only bone mineral density on relative scale, which is the PMI index, but also the absolute values of the geometric parameters (L and MI) for this age period (Table 3). From the results in   Table 3, it follows that the averaged values of the thickness of the mandible cortical layer are greater than in the Subgroups I and II individuals (Fig. 5), and significantly greater than in the Comparison Group in individuals, Subgroups III and IV, that is, the cortical jawbone is thicker in persons born with intrauterine overweight.
Also, for all PR, we calculated PMI, as is shown in Table 3, which shows that this index is higher for Subgroups III and IV even in the AP I. Therefore, this index could not indicate the prevalence of resorption processes upon the bone remodeling processes. And given the data obtained in the clinical study and the results of MI calculations, the index indicates a compensatory thickening, more pronounced in persons of Subgroups III and IV, of the mandible cortical layer.
An age-related aspect is also interesting, an increase in the value of PMI in Subgroups I, II and the Comparison Group due to the reduction of the distance between the margin of the mandible and the mental foramen, and in individuals in Subgroups III and IV, due to the thickening of the cortical layer.
Therefore, the results of our study indicate that the PMI index is informative, but its application requires additional conditions (e. g., an accurate definition of the MI index).
Densitometry. Because the densitometry is a more complicated procedure than the obtaining of the PR, this method has only been used in the studies that have been done on medical grounds to determine the bone density. From the study participants in the Main Group aged 25-55, fifteen persons were involved in determining the bone density with the densitometry, namely, seven persons (Subgroup I + Subgroup II, average age of 36.1); from participants of the total Subgroup III + IV were involved eight persons (average age of 36.0); and eight persons (average age of 36.63) from the Comparison Group.
As the Table 4 shows, the macrosomic-at-birth individuals, whose pre-natal period passed on the background of medium or relatively low height-weight index (combined group I + II), had a significantly reduced trabecular bone tissue optical density (ODT). That is, in combination with the results of the clinical examination described above, the reduction in optical density of trabecular bone tissue is the explanation of mainly inflammatory processes in the periodontium.
As can be seen from Table 4, the optical density of the cortical layer (ODC) is significantly smaller in individuals in the Combined Group III + IV, who have a larger thickness of the cortical layer. That is, in individuals with pre-natal overweight (obesity) in the past history, a compensatory thickening of a spongy cortical layer occur, along with an unreliable decrease in the density of the trabecular component of the jaw bone as compared to Control Group.
It is known that the optical density of the mandible compact layer in inflammatory diseases of the mandible is virtually unchangable quantity. Our study has shown that in non-inflammatory destructive processes in periodontal tissues occurring in ontogeny in macrosomic-at-birth individuals, who were born with signs of intrauterine obesity, a decrease in the density and thickening of the cortical layer of bone tissue occur. These phenomena are observed even in young people. The information istablished can explain the tendency for «low-inflammatory» destruction of jaw bone in such individuals. Also, given that the cortical component in the mandible occupy more than 50% of its volume, a significantly altered density of the mandible is definitely associated with a large percentage of malocclusions in such individuals [9].
The data in Table 4 shows a factor by which the cortical part of the mandible is denser than the trabecular, therefore, despite the reduced density of the cortical part of the jaw, the density of its trabecular part in persons of Subgroup III + IV is not significantly different from the Comparison Group. The ratio of Optical density of the lower jaw cortical bone/Optical density of the lower jaw trabecular bone ratio

Table 4 Mathematical expection of the optical density of lower jaw bone tissue in persons involved in the study
given in Table 4 provides us with another confirmation that the processes of jaw bone remodeling go mainly through osteosclerotic changes in such individuals. The data on the thickness of the cotrical layer of the lower jaw (MIct) and the distance between the middle of the mental foramen and the lower margin of the mandible (Lct) obtained from the tomographic images and ratio, are shown in the last three raws in Table 4, confirm the similar data we have obtained by measuring PR. These mesurements also confirm that in persons born with macrosomia with intrauterine obesity (Subgroup III + IV) the mandibular cortical layer is significantly thicker as compared to Subgroup I + II and in Main Group persons. It should be noted that the computer tomography and X-ray method are independent. Conclusions 1. Along with the known exogenous and endogenous factors that cause periodontal tissue diseases, the course of the intrauterine period forms a specific type of metabolism and has a decisive influence on the formation of dental disorders in individuals born with macrosomia.
2. According to the results of clinical dental examination obtained in our study, it follows that metabolic disorders in the pre-natal period, namely, pre-natal overweight in persons born with macrosomia, cause dystrophic-inflammatory changes in the oral cavity in ontogeny, with prevalence of an dystrophic component, which are accompanied by destruction of periodontal tissue of a different degree of severity and are manifested by atrophy of the alveolar processes, recession of the gums, and accompanied by the appearance of wedge-shaped defects.
3. The results of direct and indirect calculations of the optical density of the bone tissue indicate a significantly reduced density of the cortical layer of the bone tissue of the jaws and confirm the clinical data on the prevalence of «low-inflammatory» destructive processes in the overwhelming number of macrosomic-at-birt individuals with intrauterine overweight.
4. The intrauterine well-balanced development, as well as a relative intrauterine insufficiency of body weight in macrosomic-at-birth individuals in the later life is mainly result in dystrophic-inflammatory changes of periodontal tissues with prevalence of an inflammatory component of different degree of severity and in a significantly reduced optical density of the trabecular tissue. 5. A significantly higher percentage of individuals in the Main Group, as compared to the Comparison Group, who had retained third molars with a deviated axis of eruption serves to confirm the underdevelopment of the mandible in persons whose birth parameters were higher than normal.
Conflict of interest: The author declares no conflict of interest.