Prenatal exposure to gestational diabetes mellitus increases developmental defects in the enamel of offspring
Prenatal exposure to gestational diabetes mellitus increases developmental defects in the enamel of offspring
Tawana Pascon 0 1
Ang e?lica M. P. Barbosa 0 1
Rita C. L. Cordeiro 1
Diego G. BussaneliID 1
Caroline B. Prudencio 0 1
Sthefanie K. Nunes 0 1
Fabiane A. Pinheiro 0 1
Grasiela Bossolan 0 1
Leandro G. Oliveira 0 1
Iracema M. P. Calderon 0 1
Gabriela MariniID 1
Marilza V. C. Rudge 0 1
0 Department of Gynecology and Obstetrics, Sa?o Paulo State University (UNESP), Botucatu Medical School , Botucatu, Sa?o Paulo , Brazil , 2 Department of Physiotherapy and Occupational Therapy, Sa?o Paulo State University (UNESP), School of Philosophy and Sciences , Mar ??lia, Sa?o Paulo , Brazil , 3 Department of Pediatric Dentistry and Orthodontics, Sa?o Paulo State University (UNESP), Araraquara School of Dentistry , Araraquara, Sa?o Paulo , Brazil , 4 Health Sciences Center, University of the Sacred Heart (USC) , Bauru, Sa?o Paulo , Brazil
1 Editor: V ??ctor Sa ?nchez-Margalet, Virgen Macarena University Hospital, School of Medicine, University of Seville , SPAIN
Background and objective Gestational diabetes mellitus (GDM) is associated with short- and long-term maternal and perinatal repercussions. Our objective was to evaluate the long-term consequences of intrauterine exposure to hyperglycemia on Developmental Defects of Enamel (DDE) in offspring.
Data Availability Statement: All relevant data are
within the paper and its Supporting Information
Funding: The authors received no specific funding
for this work.
Competing interests: The authors have declared
that no competing interests exist.
Overall, 50 children of women with GDM and 250 children of normoglycemic women
participated, the latter serving as controls. Children were examined at the age between 3 and 12
years. In addition to physical examination, two independent observers examined and rated
photographs to identify specific types of DDE in a blinded fashion. Among offspring of
mothers with GDM, rates of DDE (all types combined) and hypoplasia (specific type) were
significantly higher (p<0.001, p = 0.04), in comparison to offspring of normoglycemic mothers.
Considering only the affected teeth (1060 in GDM category; 5499 in controls), rates of DDE
(all types combined) were significantly higher for total teeth (p <0.001) and deciduous teeth
(p<0.001), but not permanent teeth. In specific types of DDE involving deciduous teeth,
rates of demarcate opacity were significantly higher (p<0.001; canine and 2nd mandibular
molars) and hypoplasia (p <0.001; 2nd maxillary molars and 2nd mandibular molars). In
permanent teeth, the rate of diffuse opacity in association with GDM was significantly higher
(p<0.001; maxillary central incisors and 1st maxillary molars).
GDM was associated with the adverse effects of DDE on offspring. This study lays the
foundation for future studies to determine the impact of GDM on long-term risk of DDE.
Gestational diabetes mellitus (GDM) [
] is associated with an increased risk of
complications for both mother and baby during pregnancy as well as the postpartum period [
GDM is also associated with short- and long-term repercussions [
]. The effects of the
diabetic intrauterine environment during gestation cannot be ignored and extend beyond those
apparent at birth . Currently, infant survival is the norm, but the long-term effects on the
offspring of GDM mothers who are born today may differ from those reported many years
Several studies suggest that maternal health conditions, particularly hyperglycemia during
pregnancy, can alter fetal development to affect organ formation and increase the risk of
] however, the effects of maternal diabetes on tooth development and the
associated underlying mechanisms have not been thoroughly investigated .
Epidemiologic and animal model studies have shown that hyperglycemia changes the tooth
development process by affecting tooth eruption and mineralization [
Developmental defects of enamel (DDE) may negatively affect oral health and aesthetics,
cause tooth sensitivity, malocclusion [
] results in anesthesia difficulties because of the
]. Moreover, they are risk factors for caries lesions and erosion in children?s
The limited available studies focus on diabetes mellitus, and the animal studies have highly
heterogeneous results, which are inconclusive. Besides, most of the original studies regarding
the GDM mother?s offspring did not include data about DDE. We hypothesize that gestational
dysglicemia may affect the enamel formation initiate intrauterine life from the 14th to 32nd
gestational weeks [
Thus, objective of this study was to evaluate the long-term consequences of intrauterine
hyperglycemia exposure on DDE in offspring 3?12 years after birth. Specific analyses were
performed to determine the DDE (all types combined) rate and specific type, the DDE-affected
surface localization, and the dentition types, teeth groups and number of teeth affected
according to the intrauterine chronology of dental enamel formation.
Setting and population
This study was part of a prospective cohort study to evaluate the short- and long-term effects
of GDM on mothers and their offspring. The study was conducted in the Perinatal Diabetes
Research Center (PDRC) of Botucatu Medical School/UNESP/ Brazil from March 2016 to
September 2017. All mothers and offspring who visited the Perinatal Diabetes Research Center
between 2003 and 2013 were invited to participate. The selection of mothers and children in
the GDM group was performed at this center since it is a tertiary referral center for perinatal
Sample size estimation
The sample size was calculated based on the estimated prevalence of 7% GDM [
] and 16%
], the absence of confounders, and the prevalence of type I errors = 0.20 and type II
errors = 0.05. It was estimated that to detect differences greater or equal to 30%, 13 children
were needed for the GDM mothers (GDM) group, and 184 children were needed for the
normoglycemic mothers (NGT) control group.
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Selection of subjects
The children were included only if the mothers agreed to have a dental examination, and the
mothers were informed that they could terminate the follow-up at any time. According to the
Helsinki Declaration, written informed consent for the inclusion of their records was obtained
from the mothers of all selected children.
Access to the maternal and offspring data was approved by hospital trust administrations.
Some of the mothers did not accept our invitation, and many children did not participate in
the required clinical examination. Additionally, children with a history of systemic disease,
deciduous tooth infection or trauma in the dentomaxillofacial region were excluded from the
study. GDM was diagnosed with a 75-g glucose tolerance test (75-g GTT) as recommended by
the American Diabetes Association[
], and the glucose profile test was performed as
recommended by Rudge [
] between the 24th and 28th gestational weeks. All mothers with GDM
received glucose-lowering treatment consisting of dietary and lifestyle counseling, and no
mothers needed insulin therapy during pregnancy. The criteria for maternal and offspring
] were defined based on all variables clearly mentioned in the literature
as possible risk factors for the development of GDM. The maternal inclusion criteria were
women with a GDM or NGT diagnosis [
] and whose offspring were three to 12 years old.
The mothers and their children who accepted the invitation (n = 572) were included as
participants. Children were classified according to intrauterine hyperglycemia exposure (GDM study
group, n = 50) or intrauterine normoglycemic exposure (NGT control group, n = 250) (Fig 1).
Fig 1. Flowchart of individuals enrolled in the study.
3 / 16
A structured medical history questionnaire was sent to the subjects. Background information
solicited from the mother included gestational history, birth history, neonatal history and
infant history and was obtained in the form of self-reported questionnaires, medical records
and dental records. After their parents signed the informed consent form, the children were
examined at the ambulatory clinic according to the World Health Organization guidelines for
epidemiological studies on oral health. All data were entered in the PDRC electronic database
of Botucatu Medical School.
Prior to the examinations, a calibration exercise [
] using 41 clinical photographs of patients
obtained from the Department of Pediatric Dentistry at Araraquara Dental School was
conducted for the two examiners. A month after this exercise, the clinical photographs were
reexamined by the same two examiners, and the kappa statistics [
] were used to measure the
concordance between the examiners. The intra-examiner test agreement for DDE was
excellent (0.79 and 0.82), inter-examiner good and excellent (0.67 and 0.75) and gold standard
excellent (0.69 and 0.76; 0.76 and 0.79) reliability [
Dental clinical examination and DDE diagnostic criteria
The examinations were performed using a headlight, a plane intra-oral disposable mouth
mirror, clinical instruments, an infant C-shaped labial dental retractor and sterile gauze for teeth
cleaning and drying. The intraoral examinations were performed using biosafety material and
protection for the examiner and child. Prior to the examinations, the children?s teeth were
cleaned and dried with gauze to remove any gross plaque or food deposits that may have been
The total number of existing teeth were counted and identified as deciduous or permanent
teeth. The examinations for diagnosing DDE (all types comibined) and the specific type DDE
for all teeth surfaces were performed in accordance with FDI criteria (FDI) [
] for the Defects
of Dental Enamel Development (DDE) Index.
A probe was used to detect and confirm the presence of any tooth enamel surface
discontinuity, and the child was examined in a sitting position on a chair or lying on a stretcher. DDE
and the type of DDE were established by clinical examination, and the clinical diagnosis was
confirmed by two blinded examiners by using teeth photographs [
]. Occlusal photographs
were taken from the upper and lower arches, as well as lateral photographs on both sides and
frontal photographs, using a digital camera (Sony Cyber-Shot, 162 megapixels Exnos R, 30x
optical zoom, DSC HXICOV?HDAVCHD).
The diagnostic criteria for the occurrence of DDE and its three types (modified DDE
index) were standardized for both the clinical examiner and the examiners who confirmed the
]. The three main types of enamel defects based on macroscopic appearance,
namely, demarcated opacity, diffuse opacity and hypoplasia, were defined as the types of DDE.
Fluorosis was evaluated [
] only to differentiate it from DDE and was excluded from the
34, 36, 40
Ethical permission was obtained from the Institutional Ethical Committee of Botucatu Medical
School of S?o Paulo State University (CAAE 60537316.3.0000.5411).
4 / 16
Statistical analyses were performed using SPSS v21.0 (IBM, Armonk, NY, USA). Demographic
data were reported as the mean and standard deviation or as percentages for categorical
variables. Descriptive data analyses and odds ratios with 95% confidence intervals (CI?s) were
estimated. Non-normally distributed variables were analyzed using non-parametric tests;
chisquare and Fisher?s exact tests were used to compare qualitative demographic data. To assess
the relative strength of the association between the occurrence of GDM and DDE and various
potential risk factors unadjusted logistic regression analyses were performed. The significance
level was set at 0.05.
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the dentition of the same offspring. Only two cases of fluorosis were found in the GDM group,
and none were found in the normoglycemic group; thus, fluorosis was excluded from the
Table 3 shows, by the adjusted logistic regression model, that DDE (all types combined)
and demarcate opacity (independent variables) were associated with GDM. No association
was found between diffuse opacity or hypoplasia and GDM.
Table 4 analyzes all permanent and deciduous teeth among offspring of mothers with and
without GDM, while Fig 2 identifies specific teeth with DDE. Rates of DDE overall were
significantly higher in the presence of GDM for total teeth and deciduous teeth, but not permanent
teeth. Among specific DDE types, rates of demarcate opacity were significantly higher in
deciduous teeth (canine and 2nd mandibular molars?Fig 2A)) and hypoplasia (2nd maxillary
molars and 2nd mandibular molars?Fig 2C)). In permanent teeth, the rate of diffuse opacity in
association with GDM was significantly higher (maxillary central incisors and 1st maxillary
molars?Fig 2B)). In Fig 2, the groups of teeth with a higher rate of DDE in GDM offspring
began forming enamel at the 17th week of intrauterine life, and this process continued
throughout subsequent weeks.
Our findings showed higher rates of DDE and hypoplasia in the offspring of mothers with
gestational diabetes. The logistic model adjusted for the gender, ethnicity and BMI of the
newborns shows a higher risk of DDE and demarcated opacity in the offspring exposed to GDM.
In this study, the protocol, diagnostic criteria and classification of DDE were calibrated,
and the literature indicates that this greatly improves the quality of the studies [
diagnosis and classification of DDE were based on FDI criteria [
], and the frequency of the data
was analyzed. The conclusion that the frequency of enamel defects is exclusive to the
gestational phase is innovative; our study contributes greatly to resolving the conflict between
studies examining risk factors for DDE because it establishes a methodology that reduces the
diagnosis errors in these studies [
The prevalence of enamel defects (34.4%) found in our study for this population was similar
to that found in other Brazilian studies (29.9%) [
]. A diabetic intrauterine environment
leads to increased susceptibility to disease in offspring [
]; in our study, maternal
disorders were related to enamel defects in 26% of GDM offspring and in 8.4% of control offspring.
Our results were not in agreement with the literature, which reports rates of 40% and 70%
]; the discrepancy is likely because these studies did not use the same ineligibility criteria
as our study, which may have contributed to these lower rates. However, our findings highlight
the importance of prenatal care in preventing maternal diseases and dental enamel disorders
To analyze the prevalence of primary dentition enamel defects that began during
pregnancy, longitudinal, descriptive and retrospective quantitative studies of children between 1 to
3 years of age were carried out in a city in the south of Brazil [
]. The predominant results
showed that there were changes in the formation of primary teeth and in the appearance of
opacities and hypoplasia; these symptoms were related to systemic complications during
]. Although a correlation has not been investigated, 3.2% of mothers have gestational
diabetes; some animal [
] and human studies note that maternal systemic conditions, such as
nutritional vitamin deficiencies of calcium and phosphorus and uncontrolled gestational
diabetes, are possible factors that influence the prevalence of hypoplasia [
Guapanchi et al. is one of the rare studies that has investigated the enamel defects of diabetic
mothers; this study evaluated the occurrence of opacities beyond hypoplasia and observed a
high correlation between gestational diabetes and enamel hypoplasia [
7 / 16
Our study also evaluated children between 3?12 years of age and found that 16% of patients
in the GDM group had hypoplasia; this difference can be explained by the fact that the
Guapanchi et al. [
] study did not apply the same exclusion and ineligibility criteria.
The results found of the different types of DDE in the GDM group in our study, both in the
deciduous and in the permanent dentition are partially similar to those of Guapanchi et al. [
since we found hypoplasia in the deciduous 2nd mandibular molars and maxillary molars and
in the permanent 1st molars, maxillary canines and central incisors.
The negative impact in deciduous and permanent teeth may be impacted by due to the
onset of glycemic change during pregnancy around the 18th to the 19th week of gestation,
although the diagnosis is made weeks after this period. We demonstrated the possible
influence of GDM from the first trimester, concomitant to the beginning of dental enamel
formation (Fig 2). Our findings alert us to the need for diagnosis of GDM as soon as possible so that
preventive and minimizing measures of deleterious effects can be adopted early .
Our findings are consistent with those of animal studies conducted by Afshar et al. [
Silva-Sousa et al.[
]; in a study conducted by Noren [
], there was no control group for
comparison, but no relation was found between enamel hypoplasia and gestational diabetes [
These values cannot be compared because the percentage presented in the Guapanchi et al. [
study was calculated according to the number of affected teeth, and in the present study, this
percentage refers to the total number of teeth evaluated.
Our findings do not confirm the findings of other studies in which no associations between
diabetes during gestation and defects in enamel development were observed. Such
disagreements can be explained by the fact that the samples of these studies [
21, 42, 47, 51
3.2% and 1% of mothers with gestational diabetes; in contrast, our study used a comparative
group of mothers with gestational diabetes and another control group.
A study conducted in Hong Kong aimed to investigate the potential risk factors associated
with the occurrence of DDE in primary teeth through a prospective cohort study using a
random sample of children from the community. Diffuse opacities were the most common type
of DDE. Several possible etiological factors were considered; however, after adjusting for
confounding factors, no variable could be identified as a risk factor for DDE in this cohort study.
When analyzing the studied variables, the authors did not identify whether there were mothers
with a history of gestational diabetes or other well-established risk factors in this group [
In our group of children of diabetic mothers, we observed a difference in the occurrence of
macrosomia, which is plausible because they are children of diabetic mothers. Although we
have included this variable in the adjusted logistic regression analysis, in future studies, we
must consider the findings of Wong et al.  who observed a significant association of the
occurrence of demarcated opacities (p<0.05) for only the children with heavier birth weights.
In an experimental [
] study that used optical microscopy to analyze the enamel organ of
the mandibular incisors of the offspring of rats with alloxan-induced diabetes, no alterations
were found in the enamel organ of rats born to diabetic mothers in comparison with that of
rats born to normal mothers. In contrast, significant differences were detected with
computerassisted morphometry. These results indicate that there are structural defects in the skeletal
organ of rats born to mothers with alloxan-induced diabetes that can induce enamel
hypoplasia that can be observed by scanning electron microscopy. The authors suggest that maternal
metabolic changes are the cause of the hypoplasia. These findings support the hypoplasia
results obtained in our study, but other defects should be evaluated in experimental studies
using induced gestational diabetes models [
An experimental study that characterized the enamel hypoplasia in the offspring of rats
with alloxan-induced diabetes mellitus led to research using pregnant rats supplemented or
not with insulin and controls in which sterile saline was given instead of alloxan or insulin.
8 / 16
Fig 2. Representation of the frequency of DDE according to the intrauterine chronology of dental enamel formation in
groups of teeth and the following specific types of DDE in the teeth of the offspring of normoglycemic (NGT) and
gestational diabetes mellitus (GDM) mothers: a) demarcate opacity, b) diffuse opacity and c) hypoplasia. Legend:
Chisquare or Fisher?s exact tests. Statistically significant p values were less than 0.05.
The results showed that insulin treatment was not sufficient to prevent or reduce the
occurrence of hypoplasia [
In the critical and delicate period of fetal development, the process by which a stimulus
induces long-term impacts on the fetus, previously described and established as "fetal
programming" by Hales and Barker [
], is a new concept called "metabolic memory". All
metabolic abnormalities observed among gestational diabetic women create an in-utero
environment for the fetus that programs for diseases during adulthood [
]. This in-utero
programming seems to create a kind of "metabolic memory? since the physiological anomalies
of the gestational period are responsible for the onset of diseases when the offspring become
11, 53, 55
DDE may impact the long term individual?s health status, in both primary and permanent
dentitions. The increased porosity of teeth affected by hypomineralization increases the risk of
post-eruptive breakdowns and caries development [
] which can rapidly compromise tooth
integrity, resulting in early dental loss. Although deciduous dentition is temporary, it is
fundamental for craniofacial growth and development, mastication, speech and prevention of
abnormal habits [
], and therefore, impacting the long-term health status. It is also
noteworthy that when a DDE is detected in primary second molars, the chances of permanent teeth
also being affected is greater, since the development period of the permanent molars and
incisors coincides with that of the second primary molar [
Enamel development defects are directly related to hypocalcification, and the effects of gene
alterations already demonstrated in different animal studies [
] should be investigated in
GDM offspring to deepen our insight into the responses to this association. The chronological
analysis indicates that the groups of teeth that had a higher rate of DDE in the GDM offspring
began their enamel formation from the 17th week of intrauterine life, and this development
continued throughout subsequent weeks. A study comparing the cortical area of the humerus
as measured by neonatal radiographs in children showed that children with enamel hypoplasia
had a mean cortical area of 10.1?1.9 mm2 compared to 13.9?1.4 mm2 in children without
enamel hypoplasia (p<0.001) . These clinical findings of the positive relationship between
demineralization due to probable hypocalcemia and enamel hypoplasia support the hypothesis
that hypocalcemia in pregnancy complicated by diabetes [
] is one of the causes of the
prevalence of enamel development defects in the teeth of offspring [
30, 65, 66
This study is of paramount importance because dental enamel does not regenerate; it is a
biological marker, and these defects are a reflection of in-utero events. Furthermore, because
dental enamel defects can identify risk factors for health problems, they could auxiliary
forensic identification, because enamel does not undergo remodeling and reabsorption. It is
suggested that dental practitioners take note of these defects in routine practice and record
maternal data so that dental record information is available during possible forensic
The strength of this study is that the knowledge of the distribution of enamel defects and
the factors associated with their development allows a better understanding of the problem
and its diagnosis; furthermore, this study can contribute to establishing measures of
prevention and treatment of these defects
The American Diabetes Association (ADA) defines GDM as ?Diabetes diagnosed in the
second or third trimester of pregnancy that is not clearly overt diabetes?[
10 / 16
according to the International Association of Diabetes and Pregnancy Study Groups
(IADPSG) criteria, women can be diagnosed with GDM in even the first trimester . Thus,
Fig 2 is a graphical representation of the frequency of teeth affected by different types of DDE
for both NGT and diagnosed with GMD offspring, considering the period of dental formation
in weeks of intrauterine life. From these findings, we can suggest the possible influence of the
high glycemic index during the tooth enamel formation process. The findings of our study and
the knowledge of the chronology of early enamel formation at the onset of intrauterine life
reinforce the need to diagnose GDM to minimize the deleterious effects caused by the altered
Inevitably, the present study have limitations; some maternal and offspring variables,
such as maternal blood data during gestation and follow-up dental eruption data in the
offspring, would have given a more accurate assessment of GDM and the occurrence of DDE.
This study is the first to perform clearly prospective and quantitative assessments of GDM
and longitudinal measurements of the enamel of offspring teeth. Careful control of potential
confounders has been considered to minimize the bias of reverse causality or unmeasured
To avoid bias in the results, model adjustments were made for gender because it precedes
the occurrence of GDM and for ethnicity and BMI because they were different in the study
group. We attempted to correct for as many of the confounding variables as possible in this
study design; consequently, the design of this study is a robust alternative to assess the
adverse effects on mothers and infants. The identification of non-modifiable risk factors
that may influence the postnatal programming mechanisms of GDM in offspring is
necessary to formulate DDE prevention strategies in this high-risk group. This study significantly
advanced the current knowledge of the effects of GDM on DDE in offspring and suggests
that susceptibility to DDE may be the result of the fetal programming induced by maternal
This study also lays the foundation for future studies to determine the impact of GDM on
the long-term risk of DDE. We believe that this study has important clinical relevance since it
provides evidence of the connection between GDM and DDE and thus promotes interest in
investigating preventive and therapeutic strategies for mothers and their children to avoid or
minimize the consequences of GDM.
In conclusion, in the present study, GDM was independently associated with the adverse
effects of DDE on offspring, and the most common type of DDE that was associated with
GDM was demarcated opacity. The prevalence of DDE was significantly higher in the
offspring of GDM mothers, and the type of DDE with the highest rate of occurrence was
hypoplasia. It was also concluded that there was a higher proportion of teeth with DDE in the
offspring of GDM mothers; moreover, in the GDM group, the deciduous dentition had a
significantly higher proportion of demarcated opacity and hypoplasia, and the permanent
dentition had a significantly higher proportion of diffuse opacity. This study lays the foundation for
future studies to determine the impact of GDM on long-term risk of DDE.
S1 Fig. Frequency of developmental defects of enamel (DDE) and type of DDE between the
offspring of normoglycemic (NGT) and gestational diabetes mellitus (GDM) mothers.
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S2 Fig. Frequency of teeth with developmental defects of enamel (DDE) of the offspring of
normoglycemic (NGT) and gestational diabetes mellitus (GDM) mothers.
The authors would like to give our great appreciation to the children who participated in this
study. We would also like to thank the Academic Editor and the anonymous reviewers for
their constructive suggestions and valuable comments.
Conceptualization: Tawana Pascon, Ange?lica M. P. Barbosa, Grasiela Bossolan, Iracema M. P.
Calderon, Gabriela Marini, Marilza V. C. Rudge.
Data curation: Tawana Pascon, Ange?lica M. P. Barbosa, Caroline B. Prudencio, Sthefanie K.
Nunes, Fabiane A. Pinheiro, Marilza V. C. Rudge.
Formal analysis: Tawana Pascon, Ange?lica M. P. Barbosa, Rita C. L. Cordeiro, Diego G.
Bussaneli, Fabiane A. Pinheiro, Grasiela Bossolan, Iracema M. P. Calderon, Marilza V. C.
Funding acquisition: Tawana Pascon, Ange?lica M. P. Barbosa, Iracema M. P. Calderon,
Marilza V. C. Rudge.
Investigation: Tawana Pascon, Ange?lica M. P. Barbosa, Rita C. L. Cordeiro, Leandro G.
Oliveira, Marilza V. C. Rudge.
Methodology: Tawana Pascon, Ange?lica M. P. Barbosa, Rita C. L. Cordeiro, Caroline B.
Prudencio, Sthefanie K. Nunes, Grasiela Bossolan, Leandro G. Oliveira, Marilza V. C. Rudge.
Project administration: Tawana Pascon, Ange?lica M. P. Barbosa, Rita C. L. Cordeiro, Diego
G. Bussaneli, Leandro G. Oliveira, Iracema M. P. Calderon, Marilza V. C. Rudge.
Resources: Tawana Pascon, Ange?lica M. P. Barbosa, Marilza V. C. Rudge.
Software: Tawana Pascon, Marilza V. C. Rudge.
Supervision: Tawana Pascon, Ange?lica M. P. Barbosa, Rita C. L. Cordeiro, Diego G. Bussaneli,
Marilza V. C. Rudge.
Validation: Tawana Pascon, Marilza V. C. Rudge.
Visualization: Tawana Pascon, Ange?lica M. P. Barbosa, Rita C. L. Cordeiro, Marilza V. C.
Writing ? original draft: Tawana Pascon, Ange?lica M. P. Barbosa, Rita C. L. Cordeiro, Diego
G. Bussaneli, Caroline B. Prudencio, Sthefanie K. Nunes, Fabiane A. Pinheiro, Grasiela
Bossolan, Leandro G. Oliveira, Iracema M. P. Calderon, Gabriela Marini, Marilza V. C. Rudge.
Writing ? review & editing: Tawana Pascon, Ange?lica M. P. Barbosa, Rita C. L. Cordeiro,
Diego G. Bussaneli, Grasiela Bossolan, Iracema M. P. Calderon, Gabriela Marini, Marilza
V. C. Rudge.
12 / 16
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