Prevalência de lesões em mucosa oral durante a gravidez: uma revisão sistemática e meta-análise

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Trabalho de Conclusão de Curso

PREVALÊNCIA DE LESÕES EM MUCOSA ORAL DURANTE A GRAVIDEZ: UMA REVISÃO SISTEMÁTICA E META-ANÁLISE

João Victor Silva Bett

Universidade Federal de Santa Catarina Curso de Graduação em Odontologia

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João Victor Silva Bett

Trabalho de Conclusão de Curso submetido ao Departamento de Odontologia da Universidade Federal de Santa Catarina para a obtenção do Grau de Cirurgião-Dentista.

Orientadora: Prof.ª Dr.ª Graziela De Luca Canto

Florianópolis 2018

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João Victor Silva Bett

Este Trabalho de Conclusão de Curso foi julgado adequado para a obtenção do título de cirurgião-dentista e aprovado em sua forma final pelo Departamento de Odontologia da Universidade Federal de Santa Catarina.

Florianópolis, 01 de Outubro de 2018.

Banca Examinadora:

_________________________________________ Profª. Drª. Graziela De Luca Canto, UFSC

Orientador

_________________________________________ Profª. Drª. Carolina Amália Barcellos Silva

Membro

_________________________________________ Profª. Me Elis Ângela Batistella

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Dedicatória

Dedico este trabalho aos meus pais Edemara e Robson, por todo o amor e esforço que fizeram para minha educação. Aos meus irmãos João Paulo, Samy e Paulo Henrique por serem meu espelho do que seguir como pessoa e como profissional. Aos meus familiares, principalmente minha avó Edna, por todo apoio e carinho. Por último, a minha namorada Júlia por toda sua compreensão, paciência e amor.

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trazendo alegria aos meus pais e a todos que contribuíram para a realização deste trabalho. Agradeço aos meus pais que me apoiaram por todos esses anos que estive na universidade.

Agradeço aos meus irmãos por toda a ajuda, motivação e inspiração por cursar odontologia.

Agradeço aos meus amigos por todos esses anos de faculdade, que viraram uma nova família para mim.

Agradeço minha namorada Júlia por todo o apoio e carinho.

Agradeço à equipe COBE, principalmente a Elis, Fabio, Gilberto, Helena, Jéssica, Lia e Mariana por todo o tempo que passamos juntos nessa equipe e, além de muito aprendizado que adquiri, criei fortes laços e amizade.

Agradeço a todos os professores e servidores da UFSC que de algum jeito contribuíram para minha formação e, principalmente, a minha orientadora professora Graziela, que abriu as portas para muito aprendizado e oportunidades únicas ao participar da

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com o objetivo de ser submetido ao periódico Oral Diseases, em parceria com os pesquisadores da Universidade Federal de Santa Catarina: Drª. Graziela De Luca Canto, Dr. André Luís Porporatti, Drª. Carolina Amália Barcellos Silva, Drª Etiene de Andrade Munhoz, Me. Elis Ângela Batistella e Me. Gilberto Melo; e a pesquisadora Dra. Eliete Neves da Silva Guerra, da Universidade de Brasília.

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RESUMO

Objetivo: Avaliar a prevalência de lesões em mucosa oral durante a gravidez, por meio de uma revisão sistemática. Métodos: Foram selecionados estudos observacionais por dois revisores em um processo de duas fases. As estratégias de busca foram feitas realizadas nas bases de dados CINAHL, LILACS, LIVIVO, PubMed, Scopus, Web of Science e três bases de literatura cinzenta Google Scholar, ProQuest e OpenGrey. O risco de viés foi avaliado com a ferramenta Joanna Briggs Institute's Critical Appraisal Checklist for Studies Reporting Prevalence Data. A análise da qualidade do nível de evidência foi feita com os critérios de Grading of Recommendations Assessment, Development, and Evaluation (GRADE). A síntese dos resultados foi realizada pelo software MedCalc 1.514.8.1 (MedCalc Software, Ostend, Belgium). Resultados: 15 artigos foram incluídos para a análise qualitativa e quantitativa, com 5935 envolvidos. A prevalência geral das lesões foi de 12,4%. Hiperplasia gengival (11.4%), morsicatio buccarum (10%), candidíase oral (4,7%) e granuloma piogênico (3,2%) foram as lesões mais prevalentes. O risco de viés de maneira geral foi moderado e a qualidade do nível de evidência foi considerada muito baixa. Conclusão: As lesões da mucosa oral estiveram presentes em 1 a cada 10 gestantes, aproximadamente. A hiperplasia gengival foi a lesão mais prevalente. Sugere-se que em estudos futuros, sejam utilizados métodos diagnósticos padronizados e amostras com tamanho adequado a fim de melhorar a qualidade de evidência.

Palavras-chave: Odontologia baseada em evidências, gravidez, lesões orais, revisão sistemática.

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ABSTRACT

Objective: To assess the prevalence of oral mucosal disorders during pregnancy. Methods: Observational studies were selected by two reviewers in a two-phase process. Search strategies were applied at CINAHL, LILACS, LIVIVO, PubMed, Scopus, Web of Science, Google Scholar, Open Grey, and ProQuest. The risk of bias was assessed by two reviewers using the Joanna Briggs Institute's Critical Appraisal Checklist for Studies Reporting Prevalence Data. Synthesis of results was calculated by the software MedCalc 1.514.8.1 (MedCalc Software, Ostend, Belgium). Confidence in cumulative evidence was assessed by using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. Results: Fifteen studies met the eligibility criteria and were selected for qualitative synthesis and meta-analysis, of which 5,935 participants were enrolled. The overall prevalence of oral mucosal disorders was 12.4%. Gingival hyperplasia (11.4%), cheek biting (10%), oral candidiasis (4.7%), and pyogenic granuloma (3.2%) were the most prevalent lesions. The overall risk of bias was considered moderate and the quality of evidence was very low. Conclusion: Disorders of the oral mucosa were present in approximately 1 out of 10 pregnant women. Gingival hyperplasia was the most prevalent lesion. Further studies should apply homogeneous methodology as reference standard diagnostic criteria and adequate sample to improve the quality of evidence.

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LISTA DE FIGURAS

Figura 1 – Flow Diagram of Literature Search and Selection Criteria………..32

Figura 2 – Risk of bias summary………..33

Figura 3 – Overall meta-analysis……….34

Figura suplementar A – Gingival hyperplasia meta-analysis………....35

Figura suplementar B – Morsicatio buccarum meta-analisys...36

Figura suplementar C – Oral candidiasis meta-analysis...37

Figura suplementar D – Pyogenic granuloma meta-analisys...38

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LISTA DE TABELAS E QUADROS

Tabela 1 - Summary of descriptive characteristics of included articles……….………40 Quadro 1 - The Grading of Recommendations Assessments Development and Evaluation….…..42

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LISTA DE ABREVIATURAS E SIGLAS

Do inglês

CI: Confidence Interval

GRADE: The Grading of Recommendations Assessments Development and Evaluation MA: Meta-analysis

PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses PROSPERO: International prospective register of systematic reviews

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SUMÁRIO 1 INTRODUÇÃO ... .13 2 OBJETIVO ... 14 3 CAPÍTULO 1 ...15 APÊNDICE 1 ... 44 APÊNDICE 2 ... 48 4 CONCLUSÃO ... 50 REFERÊNCIAS ... 51

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INTRODUÇÃO

Complicações orais durante a gravidez podem ocorrer devido a alterações fisiológicas, neurológicas e hormonais do organismo feminino. Essas alterações podem ser minimizadas e controladas até o parto, após o qual, muitas regridem espontaneamente. Entretanto, quando isso não ocorre, procedimentos devem ser realizados seguindo alguns guidelines (ANNAN, 2005; TURNER, 2002). Pacientes devem ser instruídos sobre a possibilidade desses distúrbios(ANNAN, 2005). As lesões mais prevalentes na mucosa oral durante a gravidez citadas na literatura são: granuloma piogênico, hiperplasia gengival, candidíase oral, morsicatio buccarum, glossite migratória benigna, úlceras aftosas e telangiectasia. (DÍAZ GUZMÁN e CASTELLANOS SUÁREZ, 2004; ANNAN e NUAMAH, 2005; SARIFAKIOGLU, GUNDUZ e GORPELIOGLU, 2006; REZAZADEH et al., 2014; HABIB et al., 2017; SILVA DE ARAUJO FIGUEIREDO et al., 2017)

Alterações na microbiota da mucosa oral durante a gravidez podem estar relacionadas às mudanças hormonais, e com uma proporção aumentada de bactérias aeróbicas e anaeróbicas, como Bacteroidesmelaninogenicus, Prevotellaintermedia, e Porphyromonas gingivalis.(RAMOS-E-SILVA, MARTINS e KROUMPOUZOS, 2016; SILVA DE ARAUJO FIGUEIREDO et al., 2017)

A maior secreção de estrogênio promove o aumento da vascularização dos tecidos gengivais, e o aumento da concentração de mediadores químicos, como as prostaglandinas e mudanças do sistema fibrinolítico pode levar o organismo a um estado proinflamatório{Silk, 2008 #21979}, tornando a mucosa oral mais suscetível a fatores irritantes locais. O estresse e a ansiedade durante a gravidez contribuem a uma pobre higiene oral, potencialmente resultando em aumento do número de lesões intraorais.(SARIFAKIOGLU, GUNDUZ e GORPELIOGLU, 2006; SILK et al., 2008)

O conhecimento das lesões orais mais prevalentes nesse período contribui para o correto diagnóstico e manejo desses transtornos, assistindo os profissionais de saúde a fornecer informações adequadas às gestantes.

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2OBJETIVO

O objetivo geral dessa revisão sistemática foi sintetizar e realizar uma análise crítica sobre as evidências atuais em relação à prevalência de lesões da mucosa oral durante a gravidez.

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3 CAPÍTULO 1

PREVALENCE OF ORAL MUCOSAL DISORDERS DURING PREGNANCY: A SYSTEMATIC REVIEW AND META-ANALYSIS

Running title: Pregnancy and oral mucosal disorders

Authors: João Victor Silva Bett1, Elis Ângela Batistella1, Gilberto Melo1, Etiene de Andrade Munhoz2, Carolina Amália Barcellos Silva3, Eliete Neves Silva Guerra4, André Luís Porporatti1,2, Graziela De Luca Canto1,2.

1_{Brazilian Centre for Evidence-Based Research, Federal University of Santa Catarina}

(UFSC), Florianópolis, Santa Catarina, Brazil.

2_{Department of Dentistry, Federal University of Santa Catarina (UFSC), Florianópolis, Santa}

Catarina, Brazil.

3_{Department of Morphological Sciences, Federal University of Santa Catarina (UFSC),}

Florianópolis, Santa Catarina, Brazil.

4_{Laboratory of Oral Histopatology, Health Sciences Faculty, University of Brasília (UNB),}

Brasília, Brazil.

Corresponding author: JoãoVictor Silva Bett Federal University of Santa Catarina

University Campus, Mailbox 476 – Trindade, Zip code: 88040900. Florianópolis, Santa Catarina, Brazil

Telephone number: +55 48 3721 4952 E-mail: jvsbett@gmail.com

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ABSTRACT

Objective: To assess the prevalence of oral mucosal disorders during pregnancy. Methods: Observational studies were selected by two reviewers in a two-phase process. Search strategies were applied at CINAHL, LILACS, LIVIVO, PubMed, Scopus, Web of Science, Google Scholar, Open Grey, and ProQuest. The risk of bias was assessed by two reviewers using the Joanna Briggs Institute's Critical Appraisal Checklist for Studies Reporting Prevalence Data. Synthesis of results was calculated by the software MedCalc 1.514.8.1 (MedCalc Software, Ostend, Belgium). Confidence in cumulative evidence was assessed by using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. Results: Fifteen studies met the eligibility criteria and were selected for qualitative synthesis and meta-analysis, of which 5,935 participants were enrolled. The overall prevalence of oral mucosal disorders was 12.4%. Gingival hyperplasia (11.4%), cheek biting (10%), oral candidiasis (4.7%), and pyogenic granuloma (3.2%) were the most prevalent lesions. The overall risk of bias was considered moderate and the quality of evidence was very low. Conclusion: Disorders of the oral mucosa were present in approximately 1 out of 10 pregnant women. Gingival hyperplasia was the most prevalent lesion. Further studies should apply homogeneous methodology as reference standard diagnostic criteria and adequate sample to improve the quality of evidence.

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ACKNOWLEDGEMENTS

Elis Ângela Batistella is supported by CAPES (Coordination for the Improvement of Higher Education Personnel), Ministry of Education, Brazil.

Gilberto Melo is supported by CAPES (Coordination for the Improvement of Higher Education Personnel), Ministry of Education, Brazil.

CONFLICT OF INTEREST

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INTRODUCTION

Oral complications during pregnancy may occur due to physiological, neurological and hormonal changes of the female organism. These conditions can be minimized and managed satisfactorily until childbirth, since the spontaneous regressions generally occur. However, when these disorders do not regress, procedures may be performed following specific guidelines.(TURNER e AZIZ, 2002; ANNAN e NUAMAH, 2005) Patients should be instructed of the possibility of transitory nature of these conditions.(VASCONCELOS et al., 2012)

The most prevalent oral lesions during pregnancy cited in the literature are pyogenic granuloma, gingival hyperplasia, oral candidiasis, cheek biting, benign migratory glossitis, aphthous ulcers, and telangiectasia.(DÍAZ GUZMÁN e CASTELLANOS SUÁREZ, 2004; ANNAN e NUAMAH, 2005; SARIFAKIOGLU, GUNDUZ e GORPELIOGLU, 2006; REZAZADEH et al., 2014; HABIB et al., 2017; SILVA DE ARAUJO FIGUEIREDO et al., 2017)

Changes in the microbiota of the oral mucosa during pregnancy can be related to hormonal changes with an augmented proportion of anaerobic and aerobic bacteria, such as Bacteroidesmelaninogenicus, Prevotellaintermedia, and Porphyromonasgingivalis.(RAMOS-E-SILVA, MARTINS e KROUMPOUZOS, 2016; SILVA DE ARAUJO FIGUEIREDO et al., 2017) Increased secretion of estrogen promotes an augmented vascularization of the gingival tissues, which leaves oral mucosa more susceptible to local irritants. Moreover, an increase in the concentration of chemical mediators, such as prostaglandins, and changes in the fibrinolytic system may lead to a proinflammatory state.(BASTARRECHEA MILIÀN, FERNÀNDEZ RAMIREZ e MARTÍNEZ NARANJO, 2009) Stress and anxiety during pregnancy contribute to poor oral hygiene, potentially resulting in an increase in the number of intraoral lesions.(SARIFAKIOGLU, GUNDUZ e GORPELIOGLU, 2006; SILK et al., 2008)

Knowledge of the most prevalent oral lesions during this period and their etiopathogenesis contributes to a correct diagnosis and management of such disorders by assisting the health professionals and providing adequate instructions to pregnant women.{Silk, 2008 #25939}

The purpose of this systematic review (SR) was to summarize the current evidence regarding the prevalence of oral mucosal disorders that occur during pregnancy.

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METHODS

Protocol and registration

A systematic review protocol based on PRISMA-p(MOHER et al., 2015) was prepared and registered in the Prospective Register of Systematic Reviews (PROSPERO; Center for Reviews and Dissemination, University of York; and the National Institute for Health Research8), under the registration number CRD42018088806.

Eligibility criteria Inclusion criteria

The PECOS acronym (population, exposure, comparison, outcome and type of studies) was used to create the question of this SR, in which: P) women; E) pregnancy; C) none, O) prevalence of oral mucosal disorders; and S) observational studies. The inclusion criteria consisted of observational studies that investigated the prevalence of disorders of the oral mucosa in pregnant women, without language or publication time restrictions. Aphthous ulceration, benign migratory glossitis, candidiasis, cheilitis, gingival epulis,herpes associated lesions, leukoedema, lichen planus, papilloma, pemphigus, pemphigoid, pyogenic granuloma, and ulcers were considered disorders of the oral mucosa. Gingivitis and periodontitis were not assessed due to the existence of SRs and meta-analyses already existing on this topic.(XIONG et al., 2006; SRINIVAS e PARRY, 2012)

Exclusion criteria

1) Reviews, case reports, case series, book chapter, conference abstracts; 2) Studies whose authors did not report disorders of the oral mucosa or reporting only gingivitis or periodontitis; 3) Studies in which samples included participants with systemic chronic diseases (diabetes, HIV, syphilis); 4) Studies in which participants were taking medications potentially associated with disorders of the oral mucosa (anticonvulsants, calcium channel blockers, cyclosporine, nifedipine, and nitrendipine); 5) Studies in which participants were chronic alcohol consumers and/or smokers; 6) Studies with no quantitative data or when data were not possible to estimate

Information sources and search strategy

Electronic search strategies were developed for each of the following databases: CINAHL, LILACS, LIVIVO, PubMed, Scopus, and Web of Science. An additional search in the grey literature including Google Scholar, OpenGrey, and ProQuest, as well as manual search across reference lists of included studies was performed (the search strategies will be available in Appendix 1). Experts were consulted to indicate additional studies to be included.

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Software reference manager (EndNote X7, Thomson Reuters, Philadelphia, PA)(REUTERS, 2013) was used to collect references and remove duplicate articles.

Study Selection

A two-phase process was applied to select studies. In the first phase, two reviewers (J. V.B; E.A.B.) independently selected articles based on reading abstracts and titles retrieved from databases, using an online software (Rayyan, Qatar Computing Research Institute).(OUZZANI et al., 2016) Studies that did not meet the inclusion criteria were excluded. In the second phase, the same reviewers applied the eligibility criteria to the full text of studies. A third reviewer (G.M.) was consulted in case of disagreement between the first and second reviewer.

Data collection process

Information regarding author, year of publication, sample size, age range, overall prevalence of findings, partial prevalence of findings diagnostic criteria, and study design was collected.

Risk of bias between studies

The risk of bias assessment of selected studies was evaluated by two reviewers (J.V.B., E.A.B.) using the Joanna Briggs Institute Critical Appraisal Checklist for Studies Reporting Prevalence Data.(MUNN et al., 2014) A third reviewer (G.M.) was consulted in case of disagreements. Decisions about scoring were agreed upon by all reviewers before critical appraisal assessments and studies were characterized according to the following: risk of bias was categorized as “high” when the study reached up to 49% score “yes”; “moderate” when the study reached 50% to 69% score “yes”; and “low” when the study reached more than 70% score “yes”.

Summary measures

The prevalence of oral lesions in pregnant woman, expressed by means of relative or absolute frequencies and its 95% confidence intervals (CI), was considered as the main outcome.

Synthesis of results

Results were gathered and a meta-analysis of proportion was performed using the software MedCalc Statistical Software version 14.8.1 (MedCalc Software, Ostend, Belgium).(SCHOONJANS, 2016) The I2 test was applied to assess levels of heterogeneity. When I2 values were lower than 50%, a fixed effect model was applied. A random effect model was applied whenever I2 values were greater than 50%.(HIGGINS e THOMPSON,

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Quality of evidence assessment

The Grading of Recommendations Assessment, Development and Evaluation (GRADE) evidence profile was used to verify the overall quality of evidence. Table 2 was generated using the online software version (GRADEpro GDT).(GRADEPRO, 2016)

RESULTS Study selection

In phase-one, 3,508 articles were collected from databases. After duplicated references were removed, 1,833 studies remained. A comprehensive evaluation of titles and abstracts resulted in exclusion of 1,803 articles. One additional article(APEKSHA S. DHOLE, 2014) was selected from the reference lists of included studies. A full-text review was conducted on 31 studies on phase-one. This process resulted in the exclusion of 16 articles (Appendix 2) and 15 articles remained for final analysis.(GRIDLY, 1954; LAWOYIN et al., 2003; DÍAZ GUZMÁN e CASTELLANOS SUÁREZ, 2004; ANNAN e NUAMAH, 2005; SARIFAKIOGLU, GUNDUZ e GORPELIOGLU, 2006; TORABI, NAJAFI e MSKANI, 2006; BASTARRECHEA MILIÀN, FERNÀNDEZ RAMIREZ e MARTÍNEZ NARANJO, 2009; MORET et al., 2009; KHATIBI et al., 2013; PATIL et al., 2013; APEKSHA S. DHOLE, 2014; NEJAD, BIGOMTAHERI e AZIMI, 2014; JAIN e KAUR, 2015; HABIB et al., 2017; KIA et al., 2017) A flowchart detailing this process is available in Figure 1.

Study characteristics

The studies were conducted in nine countries: Egypt(GRIDLY, 1954), Ghana(ANNAN e NUAMAH, 2005), India(PATIL et al., 2013; APEKSHA S. DHOLE, 2014; JAIN e KAUR, 2015), Iran(TORABI, NAJAFI e MSKANI, 2006; KHATIBI et al., 2013; NEJAD, BIGOMTAHERI e AZIMI, 2014; REZAZADEH et al., 2014; KIA et al., 2017), Mexico(DÍAZ GUZMÁN e CASTELLANOS SUÁREZ, 2004), Nigeria(LAWOYIN et al., 2003), Pakistan(HABIB et al., 2017), Turkey(SARIFAKIOGLU, GUNDUZ e GORPELIOGLU, 2006) and Venezuela.(MORET et al., 2009) All studies were published between 1954 and 2017, in English(GRIDLY, 1954; DÍAZ GUZMÁN e CASTELLANOS SUÁREZ, 2004; ANNAN e NUAMAH, 2005; SARIFAKIOGLU, GUNDUZ e GORPELIOGLU, 2006; BASTARRECHEA MILIÀN, FERNÀNDEZ RAMIREZ e MARTÍNEZ NARANJO, 2009; PATIL et al., 2013; APEKSHA S. DHOLE, 2014; NEJAD, BIGOMTAHERI e AZIMI, 2014; REZAZADEH et al., 2014; JAIN e KAUR, 2015; HABIB et al., 2017; KIA et al., 2017), Persian(TORABI, NAJAFI e MSKANI, 2006; KHATIBI et

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al., 2013) and Spanish language(MORET et al., 2009). In all studies, oral specialists performed the oral examination of pregnant women.

Risk of bias within studies.

Risk of bias was judged as moderate in nine studies(ANNAN e NUAMAH, 2005; TORABI, NAJAFI e MSKANI, 2006; MORET et al., 2009; PATIL et al., 2013; APEKSHA S. DHOLE, 2014; REZAZADEH et al., 2014; JAIN e KAUR, 2015; HABIB et al., 2017; KIA et al., 2017) and low in six articles.(GRIDLY, 1954; LAWOYIN et al., 2003; DÍAZ GUZMÁN e CASTELLANOS SUÁREZ, 2004; SARIFAKIOGLU, GUNDUZ e GORPELIOGLU, 2006; KHATIBI et al., 2013; NEJAD, BIGOMTAHERI e AZIMI, 2014) In the low risk of bias group, two studies did not present samples of adequate size.(DÍAZ GUZMÁN e CASTELLANOS SUÁREZ, 2004; SARIFAKIOGLU, GUNDUZ e GORPELIOGLU, 2006) Other two articles from the low risk group(LAWOYIN et al., 2003; KHATIBI et al., 2013) did not perform histopathological analysis, thus not achieving standard diagnostic criteria for all participants.

Risk of bias across studies.

In general, studies had moderate risk of bias, due to small sample sizes and heterogeneous diagnostic criteria for oral disorders.(NEVILLE et al., 2015)

Results of individual studies.

Study’s sample sizes ranged from 86to 1,600 participants of which 5,935 participants were assessed in this study, and age of pregnant woman ranged from 10 to 50 years. The overall prevalence of oral mucosal disorders in pregnant women varied substantially, ranging from 0.22%to 31%. A great variety of lesions were identified in pregnant women. The main lesions were gingival hyperplasia(11.4%)(GRIDLY, 1954; TORABI, NAJAFI e MSKANI, 2006; MORET et al., 2009; JAIN e KAUR, 2015), morsicatio buccarum (10%)(SARIFAKIOGLU, GUNDUZ e GORPELIOGLU, 2006; APEKSHA S. DHOLE, 2014; REZAZADEH et al., 2014) oral candidiasis(4.7%)(SARIFAKIOGLU, GUNDUZ e GORPELIOGLU, 2006; APEKSHA S. DHOLE, 2014; REZAZADEH et al., 2014), pyogenic granuloma(3.2%)(GRIDLY, 1954; LAWOYIN et al., 2003; DÍAZ GUZMÁN e CASTELLANOS SUÁREZ, 2004; ANNAN e NUAMAH, 2005; TORABI, NAJAFI e MSKANI, 2006; KHATIBI et al., 2013; PATIL et al., 2013; APEKSHA S. DHOLE, 2014; NEJAD, BIGOMTAHERI e AZIMI, 2014; REZAZADEH et al., 2014; HABIB et al., 2017; KIA et al., 2017), and benign migratory glossitis(2.9%)(DÍAZ GUZMÁN e CASTELLANOS SUÁREZ, 2004; SARIFAKIOGLU, GUNDUZ e GORPELIOGLU, 2006; MORET et al., 2009; APEKSHA S. DHOLE, 2014; REZAZADEH et al., 2014). The prevalence of gingival

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hyperplasia among the articles varied from 2.9% to 25%. Pyogenic granuloma’s prevalence ranged from 0.22 % to 16.6% between studies.(GRIDLY, 1954; LAWOYIN et al., 2003; DÍAZ GUZMÁN e CASTELLANOS SUÁREZ, 2004; ANNAN e NUAMAH, 2005; TORABI, NAJAFI e MSKANI, 2006; KHATIBI et al., 2013; PATIL et al., 2013; APEKSHA S. DHOLE, 2014; NEJAD, BIGOMTAHERI e AZIMI, 2014; REZAZADEH et al., 2014; HABIB et al., 2017; KIA et al., 2017). Three studies(SARIFAKIOGLU, GUNDUZ e GORPELIOGLU, 2006; APEKSHA S. DHOLE, 2014; REZAZADEH et al., 2014) considered morsicatio buccarum as a disorder and its prevalence varied from 3.5% to 31%. Oral candidiasis prevalence varied from 1% to 15%(6,14,20). Table 1 provides details regarding studies characteristics and the prevalence of all oral lesions of each study.

Synthesis of Results

A total of 5,935 participants were included in meta-analyses. A substantial heterogeneity was observed, the pooled prevalence of oral disorders, with exception of benign migratory glossitis, was calculated on the random effect model, according to the standard approach.(HIGGINS e THOMPSON, 2002; HIGGINS et al., 2003) The overall prevalence rate (PR) of lesions was 12.4% (I²: 98%, CI: 6.8%-19.3%), and for each disorder the values of prevalence, the I2_{test, and respective 95% confidence intervals (95%CI) were as follows:}

hyperplasia = 11.4% (I2_{: 96.88%, CI: 3.0-24.3); morsicatio buccarum = 10% (I}2_{: 96.42%, CI:}

1.37-25.43); oral candidiasis = 4.7% (I2_{: 91.87%, CI: 0.66-12.2); pyogenic granuloma = 3.2%}

(I2_{: 89.82%; CI: 1.82-5.07%); and benign migratory glossitis = 2.9% (I}2_{: 0.0%, CI: 2.06-4.13).}

The quality of evidence assessment (GRADE) was considered very low in all meta-analysis. Small sample sizes, wide confidence intervals, high methodological heterogeneity of diagnostic methods, study design (observational studies) did not allow assessing patients along trimesters were the explanations for very low quality of evidence.

DISCUSSION

Summary of evidence

This SR sought to investigate the available evidence of oral mucosal disorders in pregnant women, their prevalence and characteristics. This study included 15 articles, in wich 5935 participants were enrolled. The overall risk of bias across studies was set as moderate. The main sources of bias were inadequate sample sizes, difficulty of obtaining a significant number of pregnant patients for cross-sectional studies, as most of these researches assessed patients from gynecology and obstetrics clinics.(ANNAN e NUAMAH, 2005; SARIFAKIOGLU, GUNDUZ e GORPELIOGLU, 2006) The overall prevalence rate of oral

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mucosal lesion was 12.4%. Gingival hyperplasia was the most prevalent lesion (11.4%), followed by morsicatio buccarum (10%), oral candidiasis (4.7%), pyogenic granuloma (3.2%) and benign migratory glossitis (2.9%).

Unfortunately, due to methodological limitations attributable to cross-sectional design, most studies did not present data regarding pregnancy stage in which the lesion occurred. Although, five studies divided the frequency of lesions by trimesters, in which second and third trimesters exhibited higher prevalence of disorders of the oral mucosa.(ANNAN e NUAMAH, 2005; PATIL et al., 2013; JAIN e KAUR, 2015; HABIB et al., 2017; KIA et al., 2017) This could be explained due the hormonal peaks occur as the end of gestation approaches.(GÜNCÜ, TÖZÜM e ÇAGLAYAN, 2005) Estrogen can reach up to 30 times more than its level during the menstrual cycle, and progesterone levels can reach up to 10 times, leading consequences to periodontium and the oral mucosa.(MARIOTTI, 1994) These hormonal exacerbations promote the increase of vascular permeability as well as in the flow rate of the crevicular fluid.(JENSEN, LILJEMARK e BLOOMQUIST, 1981) According to Güncü et al., 2005(GÜNCÜ, TÖZÜM e ÇAGLAYAN, 2005), estrogen promotes the reduction of the keratinization of periodontal tissues and thereby reduces the efficacy of the epithelial barrier. Higher levels of progesterone facilitate the action of local irritating factors, such as oral microbiota, causing disorders of the oral mucosa such as periodontal inflammation, gingival hyperplasia, and the onset of pyogenic granuloma.(SALOMON e MUN, 1994; KUO, C. e T., 2002; ANNAN e NUAMAH, 2005)

Pyogenic granuloma had a variation of prevalence of 0.22 to 14.2% among the studies.(TORABI, NAJAFI e MSKANI, 2006; NEJAD, BIGOMTAHERI e AZIMI, 2014) Only three studies(GRIDLY, 1954; DÍAZ GUZMÁN e CASTELLANOS SUÁREZ, 2004; NEJAD, BIGOMTAHERI e AZIMI, 2014) utilized biopsy for definitive diagnostic. One study(SARIFAKIOGLU, GUNDUZ e GORPELIOGLU, 2006) performed culture for diagnosis. Considering the clinical and etiological similarity of some pathologies, histopathological analysis is necessary to definitive diagnosis, such as in the case of pyogenic granuloma, which is clinically similar to peripheral giant cell granuloma, inflammatory fibrous hyperplasia, and peripheral ossifying fibroma.(REDDY et al., 2012; NEVILLE et al., 2015; DUTRA et al., 2018) To not perform biopsies for diagnostic confirmation can be explained because the appropriate period for biopsy is the second trimester. If the patient's function is not being affected, the lesion remission should be awaited. In cases which there are no regression of the lesion, postpartum biopsy is indicated(TURNER e AZIZ, 2002;

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RUSSELL e MAYBERRY, 2008). Some lesions rarely require biopsy for diagnosis, such as geographic tongue and cheek biting.(NEVILLE et al., 2015)

The decrease of salivary pH levels during the gestational trimesters is related to the decrease of the salivary bicarbonate buffer, reflux and frequent vomiting, shifting the oral microbiota, leading to an increase of yeasts, consequently causing the manifestation of oral candidiasis.(SARIFAKIOGLU, GUNDUZ e GORPELIOGLU, 2006; APEKSHA S. DHOLE, 2014; REZAZADEH et al., 2014; JAIN e KAUR, 2015)

The frequent act of cheek biting causes white and thickened areas, associated with erosion or traumatic ulceration or not, at the level of the occlusal plane in the buccal mucosa, known as morsicatio buccarum.(NEVILLE et al., 2015) During pregnancy, weight gain (may increase cheek fat) coupled with stress and anxiety could be related to this disorder.(OBERMAYER, 1964; IB, 1971; OBEL et al., 2005; SARIFAKIOGLU, GUNDUZ e GORPELIOGLU, 2006)

The literature reports the increase of benign migratory glossitis disorder when associated with psoriasis.(DANESHPAZHOOH et al., 2004; ZARGARI, 2006; COSTA et al., 2009; NEVILLE et al., 2015) The included studies(DÍAZ GUZMÁN e CASTELLANOS SUÁREZ, 2004; SARIFAKIOGLU, GUNDUZ e GORPELIOGLU, 2006; MORET et al., 2009; APEKSHA S. DHOLE, 2014; REZAZADEH et al., 2014) presented a prevalence of 2.97% of this disorder, nevertheless, there is no evidence linking benign migratory glossitis and pregnancy.(ASSIMAKOPOULOS et al., 2002; DÍAZ GUZMÁN e CASTELLANOS SUÁREZ, 2004; SARIFAKIOGLU, GUNDUZ e GORPELIOGLU, 2006; MORET et al., 2009; APEKSHA S. DHOLE, 2014)

Even after the current evidence pointing out the importance of pregnant women to have dental appointments during pregnancy.(LYDON-ROCHELLE et al., 2004; PIRIE et al., 2007; STRAFFORD, SHELLHAAS e HADE, 2008; VASCONCELOS et al., 2012) Several patients and health professionals still feel afraid that dental procedures can lead to problems in the gestational period that result on consequences for the fetus(AJESH et al., 2012; BAHRAMIAN et al., 2018). The specialists should follow the current guidelines to attend pregnant women, postponing surgeries and elective procedures, and the pregnant woman should have dental follow-up during pregnancy.(TURNER e AZIZ, 2002; KURIEN et al., 2013)

Health professionals should be aware of the most frequent complications that affect each patient profile. When assisting pregnant women, the team of professionals who attend these patients should be aware of the changes that occurr during this period. If clinicians are

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aware of which are the most frequent lesions in this period, they may contribute to a more effective treatment of their patients, leading greater security and prevention of stomatological diseases.

Limitations

There were limitations to the overall quality of evidence in the studies, such as the studies’ design, heterogeneous methodologies, different diagnostic criteria and inadequate sample’s sizes.

CONCLUSION

The overall prevalence of oral disorders during pregnancy was 12.4%. Gingival hyperplasia, morsicatio buccarum, oral candidiasis and pyogenic granuloma were the most prevalent lesions in the oral mucosa in pregnant women. Further studies regarding homogeneous methodology as reference standard diagnostic criteria and adequate sample sizes could improve the assessment of the disorders, and the quality of evidence.

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Figure legends

Figure 1 - Flow Diagram of Literature Search and Selection Criteria. Figure 2 - Risk of Bias Summary

Figure 3 – Overall meta-analysis Suplemmental figures legends

Figure A – Gingival hyperplasia meta-analysis Figure B – Cheek biting meta-analysis

Figure C – Oral candidiasis meta-analysis Figure D – Pyogenig granuloma meta-analysis Figure E – Benign migratory glossitis meta-analysis Table legends

Table 1 - Summary of descriptive characteristics of included studies (n=15). Table 2 - GRADE quality of evidence.

Appendix legends

Appendix 1 - Databases and search strategies

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Table 1 - Summary of descriptive characteristics of included articles (n=15). Author, Year; Country Sample _size Age range ± Standard _{Deviation (years)} prevalence of Overall

findings n (%)

Partial prevalence of

findings n (%) Diagnostic criteria Annan et al., 2005; Ghana 100 15- 39 4 (4%) AU (minor): 1 (1%)

PG: 3 (3%) Physical examination

Apeksha et al., 2014; India 492 NR 79 (16.5%)* CB: 18* (3.7%) LEU: 14* (3%) AU: 13* (2.8%) OC: 12* (2.6%) BMG: 12* (2.4%) PG: 10* (2%) Physical examination

Gridly et al., 1954; Egypt 1002 17-38 57 (5.7%) PG: 27 (2.7%)

GH: 30 (3%) Physical examination, biopsy, histopathological Guzman and Suárez et al., 2004; Mexico 93 33.16 12 (12.6%) AU: 1 (1%)

BMG: 3 (3.2%) LEU: 5 (5.3%) HPV: 1 (1%) PG: 2 (2.1%)

Physical examination, biopsy, histopathological

Habib et al., 2010; Pakistan 86 NR 4 (4.6%) AU (minor): 2 (2.3%)

PG: 2 (2.3%) Physical examination

Jain et al., 2015; India 120 18-35 63 (52.5%) AU: 1 (0.8%) FT: 24 (20%) MEL: 12 (10%*) GH: 26 (21.6%)

Physical examination

Khatibi et al., 2013; Iran 1600 26.8 72 (4.5%) PG: 72 (4.5%) Physical examination Kia et al., 2017; Iran 300 26.6±4.5 3 (1%) PG:3 (1%) Physical examination Lawoyin et al., 2003; Nigeria 400 15-50 (ma.: 29.8) 15 (3.7%) PG: 15 (3.7%) Physical examination

Nejad et al., 2014; Iran 923 17-41 (ma: 27.7±4.7) 2 (0.22%) PG: 2 (0.2%) Physical examination, biopsy, histopathological

Patil et al., 2017; India 120 17-40 (ma: 23.5) 12 (10%) AU (minor): 2 (1.6%)

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Rezazadeh et al., 2014; Iran 200 ma: 30.23 47 (23.5%) BMS: 10 (5%) BMG: 5 (2.5%) FT: 1 (0.5%) LP: 2 (1%) OC: 2 (1%) PG: 3 (1.5%) PAR: 8 (4%) CB: 7 (3.5%) PET: 5 (3%) FIB: 1 (0.5%) MUC: 1 (0.5%) HPV: 2 (1%) Physical examination

Sarifakioglu et al., 2006; Turkey 100 17-42 71/ (71%) AU: 3(3%) BMG: 5 (5%) CB: 31 (31%) FS: 4 (4%) FT: 6 (6%) HT: 10 (10%) OC: 15 (15%) TU: 4 (4%) Physical examination,culture

Torabi et al., 2006; Iran 148 ma 23.8 y 21 (14.2%*) PG: 21 (14.2%)

GH: 37 (25%*) Physical examination

Yuli et al., 2008; Venezuela 251 10-49 32 (12.7%) AU: 14 (5.5%*) GH: 10 (3.9%*) TF: 2 (0.7%*) LTP: 10 (3.9%) BMG: 7 (2.7%) CHE: 1 (0.39%) FT: 4 (1.5%) LEU2: 6 (2.3%) HER: 6 (2.3%) Physical examination

MA= mean age; NR= Not reported. AU: Aphtous ulceration; BMG: Benign migratory glossitis; BMS: Burning mouth syndrome; CB: Cheek biting; CHE: Cheilitis; FIB: Fibroma; FD: Fordyce spots; FT: Fissured tongue; Gingival hyperplasia: GH; HER: Herpes; HPV: HPV-related lesions; LEU: Leukoedema; LEU2: Leukoplakia; LTP: Loss of tongue papillae; OC: Oral candidiasis; PAR: Parulis; PET: Petechiae; PG: Pyogenic granuloma (pregnancy tumor); RAS: Recurrent aphtous stomatitis; TF: Traumatic fibroma; TU: Traumatic Ulcer. *= Estimated by the authors (P.S.: In Apeksha’s study, absolute frequencies were rounded up according to the percentage to reach the number of subjects presenting oral lesions).

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Table 2 - GRADE quality of evidence.

Certainty assessment № of patients Certainty

№ of

studies Study design Risk of bias Inconsistency Indirectness Imprecision

Other

considerations Cases/Total Aphtous Ulceration

8 Observational

studies

seriousa _{not serious} _{not serious} _seriousb _none _{37/2344 (1.6%)}

⨁◯◯◯ VERY LOW Benign Migratory Glossitis

5 Observational

studies

⨁◯◯◯ VERY LOW Gingival Hyperplasia

4 Observational

studies

seriousa _seriousc _seriousd _{not serious} _none _103/1521

(6.8%)

⨁◯◯◯ VERY LOW

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3 Observational studies

⨁◯◯◯ VERY LOW Oral Candidiasis

3 Observational

studies

seriousa _{not serious} _seriousd _seriousb _none _{29/792 (3.7%)}

⨁◯◯◯ VERY LOW Pyogenic Granuloma

12 Observational

studies

seriousa _seriousc _seriousd _seriousb _none _170/5464

(3.1%)

⨁◯◯◯ VERY LOW

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Appendix 1– Databases and search strategies

Database Search query

2017, July 14th

CINAHL

("pregnancy" OR "pregnant" OR "gestation") AND (("Oral Manifestations" OR "Oral Manifestation" OR "oral lesion" OR "oral lesions" OR "oral alteration" OR "oral alterations" OR "oral pathology" OR "oral pathologies" OR "oral complications" OR "oral complication" OR "oral changes" OR "oral change" OR "oral diseases" OR "aphtae" OR "aphtous" OR "burning mouth" OR "oral Candidiasis" OR "oral Leukoedema" OR "Oral Lichen Planus" OR "cheilitis" OR "herpes labialis" OR "labial herpes" OR "oral herpes" OR "oral mucositis" OR "oral ulcer" OR "mouth ulcer" OR "Stomatitis" OR "Geographic Tongue" OR "gingival epulis" OR "oral papilloma" OR "pyogenic granuloma" OR "pregnancy tumor" OR "granuloma gravidarum") OR (("Pemphigoid" OR "Pemphigoids" OR "Pemphigus") AND ("buccal" OR "oral" OR "mouth")))

PubMed

("pregnancy"[MeSH Terms] OR "pregnancy"[All Fields] OR "pregnant"[All Fields] OR "gestation"[All Fields]) AND ("Oral Manifestations"[MeSH Terms] OR "Oral Manifestations"[All Fields] OR "Oral Manifestation"[All Fields] OR "oral lesion"[All Fields] OR "oral lesions"[All Fields] OR "oral alteration"[All Fields] OR "oral alterations"[All Fields] OR "oral pathology"[All Fields] OR "oral pathologies"[All Fields] OR "oral complications"[All Fields] OR "oral complication"[All Fields] OR "oral changes"[All Fields] OR "oral change"[All Fields] OR "oral diseases"[Title/Abstract] OR "aphtae"[All Fields] OR "aphtous"[All Fields] OR "burning mouth"[All Fields] OR "Candidiasis, Oral"[MeSH Terms] OR "oral Candidiasis"[All Fields] OR "Leukoedema, Oral"[MeSH Terms] OR "oral Leukoedema"[All Fields] OR "Lichen Planus, Oral"[MeSH Terms] OR "Oral Lichen Planus"[All Fields] OR "cheilitis"[All Fields] OR "herpes labialis"[All Fields] OR "labial herpes"[All Fields] OR "oral herpes"[All Fields] OR "oral mucositis"[All Fields] OR "Oral Ulcer"[MeSH Terms] OR "oral ulcer"[All Fields] OR "mouth ulcer"[All Fields] OR "Stomatitis"[Mesh:noexp] OR "Stomatitis"[All Fields] OR "Stomatitis, Aphthous"[Mesh] OR "Stomatitis, Herpetic"[Mesh] OR "Glossitis, Benign Migratory"[Mesh] OR "Geographic Tongue"[All Fields] OR "gingival epulis"[All Fields] OR "oral papilloma"[All Fields] OR "pyogenic granuloma"[All Fields] OR "pregnancy tumor"[All Fields] OR "granuloma gravidarum"[All Fields] OR (("Pemphigoid, Bullous"[Mesh] OR "Pemphigoid"[All Fields] OR "Pemphigoids"[All Fields] OR "pemphigoid gestationis"[MeSH Terms] OR "Pemphigus"[Mesh] OR "Pemphigus"[All Fields]) AND ("buccal"[Title/Abstract] OR "oral"[Title/Abstract] OR "mouth"[All Fields])))

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OR "oral lesion" OR "oral lesions" OR "oral alteration" OR "oral alterations" OR "oral pathology" OR "oral pathologies" OR "oral complications" OR "oral complication" OR "oral changes" OR "oral change" OR "oral diseases" OR "aphtae" OR "aphtous" OR "burning mouth" OR "oral Candidiasis" OR "oral Leukoedema" OR "Oral Lichen Planus" OR "cheilitis" OR "herpes labialis" OR "labial herpes" OR "oral herpes" OR "oral mucositis" OR "oral ulcer" OR "mouth ulcer" OR "Stomatitis" OR "Geographic Tongue" OR "gingival epulis" OR "oral papilloma" OR "pyogenic granuloma" OR "pregnancy tumor" OR "granuloma gravidarum" OR "manifestacao oral" OR "manifestaçoes orais" OR "lesao oral" OR "lesoes orais" OR "lesao bucal" OR "lesoes bucais" OR "alteraçao oral" OR "alteraçoes orais" OR "patologia oral" OR "patologias orais" OR "complicaçao oral" OR "complicaçoes orais" OR "mudanças orais" OR "mudança oral" OR "doenças orais" OR "afta" OR "síndrome da ardencia bucal" OR "candidíase oral" OR "leucoedema oral" OR "liquen plano bucal" OR "queilite" OR "herpes labial" OR "herpes oral" OR "mucosite oral" OR "úlcera oral" OR "úlcera bucal" OR "estomatite" OR "língua geográfica" OR "epulis gengival" OR "papiloma oral" OR "granuloma piogenico" OR "tumor gravídico" OR "manifestación oral" OR "manifestaciones orales" OR "lesión oral" OR "lesiones orales" OR "cambios orales" OR "patología oral" OR "patologías orales" OR "complicación oral" OR "complicaciones orales" OR "cambios orales" OR "cambio oral" OR "enfermedades orales" OR "afta" OR "síndrome de la ardencia bucal" OR "candidiasis oral" OR "leucoedema oral" OR "liquen plano bucal" OR "úlcera oral" OR "úlcera oral" OR "úlcera bucal" OR "estomatitis" OR "lengua geográfica" OR "epulis gingival" OR "papiloma oral" OR "herpes labial" OR "herpes labial" OR "granuloma piogénico" OR "tumor del embarazo" OR (("Pemphigoid" OR "Pemphigoids" OR "Pemphigus" OR "penfigoide" OR "penfigoides" OR "penfigo") AND ("buccal" OR "oral" OR "mouth" OR "bucal" OR "oral" OR "boca")))) AND (instance:"regional") AND ( db:("LILACS"))

LIVIVO

SCOPUS TITLE-ABS-KEY("pregnancy" OR "pregnant" OR "gestation") AND TITLE-ABS-KEY ("Oral Manifestations" OR "Oral Manifestation" OR "oral lesion" OR "oral lesions" OR "oral alteration" OR "oral alterations" OR "oral pathology" OR "oral pathologies" OR

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"oral complications" OR "oral complication" OR "oral changes" OR "oral change" OR "oral diseases" OR "aphtae" OR "aphtous" OR "burning mouth" OR "oral Candidiasis" OR "oral Leukoedema" OR "Oral Lichen Planus" OR "cheilitis" OR "herpes labialis" OR "labial herpes" OR "oral herpes" OR "oral mucositis" OR "oral ulcer" OR "mouth ulcer" OR "Stomatitis" OR "Geographic Tongue" OR "gingival epulis" OR "oral papilloma" OR "pyogenic granuloma" OR "pregnancy tumor" OR "granuloma gravidarum" OR (("Pemphigoid" OR "Pemphigoids" OR "Pemphigus") AND ("buccal" OR "oral" OR "mouth"))) AND ( LIMIT-TO ( DOCTYPE,"ar" ) OR LIMIT-TO ( DOCTYPE,"ip" ) )

Web of Science

TS=(("pregnancy" OR "pregnant" OR "gestation") AND (("Oral Manifestations" OR "Oral Manifestation" OR "oral lesion" OR "oral lesions" OR "oral alteration" OR "oral alterations" OR "oral pathology" OR "oral pathologies" OR "oral complications" OR "oral complication" OR "oral changes" OR "oral change" OR "oral diseases" OR "aphtae" OR "aphtous" OR "burning mouth" OR "oral Candidiasis" OR "oral Leukoedema" OR "Oral Lichen Planus" OR "cheilitis" OR "herpes labialis" OR "labial herpes" OR "oral herpes" OR "oral mucositis" OR "oral ulcer" OR "mouth ulcer" OR "Stomatitis" OR "Geographic Tongue" OR "gingival epulis" OR "oral papilloma" OR "pyogenic granuloma" OR "pregnancy tumor" OR "granuloma gravidarum") OR (("Pemphigoid" OR "Pemphigoids" OR "Pemphigus") AND ("buccal" OR "oral" OR "mouth"))))

Grey Literature Google

Scholar

("pregnancy" OR "pregnant" OR "gestation") AND ("Oral Manifestations" OR "Oral Manifestation" OR "oral lesion" OR "oral lesions" OR "oral alteration" OR "oral alterations" OR "oral pathology" OR "oral pathologies")

Open Grey

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ProQuest

all(("pregnancy" OR "pregnant" OR "gestation")) AND all(("Oral Manifestations" OR "Oral Manifestation" OR "oral lesion" OR "oral lesions" OR "oral alteration" OR "oral alterations" OR "oral pathology" OR "oral pathologies" OR "oral complications" OR "oral complication" OR "oral changes" OR "oral change" OR "oral diseases" OR "aphtae" OR "aphtous" OR "burning mouth" OR "oral Candidiasis" OR "oral Leukoedema" OR "Oral Lichen Planus" OR "cheilitis" OR "herpes labialis" OR "labial herpes" OR "oral herpes" OR "oral mucositis" OR "oral ulcer" OR "mouth ulcer" OR "Stomatitis" OR "Geographic Tongue" OR "gingival epulis" OR "oral papilloma" OR "pyogenic granuloma" OR "pregnancy tumor" OR "granuloma gravidarum") OR (("Pemphigoid" OR "Pemphigoids" OR "Pemphigus") AND ("buccal" OR "oral" OR "mouth")))

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Appendix 2 - Articles excluded and the reasons for exclusion (n=16).

Reference Authors Reasons for Exclusion*

1 Arafat et al. (1973) 1 2 Azoifeta et al. (2014) 1 3 Bastarrechea et al. (2009) 1 4 Ghalayani et al. (2013) 2 5 Hatziotis et al. (1972) 2 6 Iyengar et al. (1973) 2 7 Lacalzadapastor et al. (2011) 1 8 Larez et al. (2005) 3 9 Lieff et al. (2004) 1 10 Rio et al. (2015) 1 11 Rivero et al. (2004) 2 12 Selvi et al. (2017) 2 13 Shulman et al. (2006) 2 14 Thomaz et al. (2015) 1 15 Wandera et al. (2012) 1 16 Yun et al. (2005) 1

1) The study did not present oral mucosal disorders. 2) The study did not present enough quantitative data.

3) The study included patients with Acquired immunodeficiency syndrome (AIDS). References of Appendix 2

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1. Arafat AH. Periodontal status during pregnancy. Journal of Periodontology. 1974;45(8):641-3.

2. Azofeifa A, Yeung LF, Alverson C, Beltrán-Aguilar E. Peer reviewed: oral health conditions and dental visits among pregnant and nonpregnant women of childbearing age in the United States, national health and nutrition examination survey,

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3. Bastarrechea Milián M, Fernández Ramirez L, Martínez Naranjo T. La embarazada y su atención estomatológica integral como grupo priorizado.: Área de salud Moncada. Revista cubana de Estomatología. 2009;46(4):60-9.

4. Ghalayani P, Tavangar A, Nilchian F, Khalighinejad N. The comparison of salivary level of estrogen and progesterone in 1st, 2nd and 3rd trimester in pregnant women with and without geographic tongue. Dental research journal. 2013;10(5):609. 5. Hatziotis JC. The Incidence of Pregnancy Tumors and Their Probable Relation to the Embryo's Sex. Journal of periodontology. 1972;43(7):447-8.

6. Iyengar L. Oral lesions in pregnancy. The Lancet. 1973;301(7804):680-1.

7. Lacalzada-Pastor M, Gil-Samaniego J, Giménez-Juncosa M, López-López J, Chimenos-Küstner E. Estado periodontal y de la mucosa oral en un grupo de embarazadas: Estudio clínico. Avances en Periodoncia e Implantología Oral. 2011;23(2):123-8.

8. Lárez L, Benavides Y, Henríquez Y, Moreno S. Lesiones bucales vistas en la embarazada. Revista de Obstetricia y Ginecología de Venezuela. 2005;65(1):9-13. 9. Lieff S, Boggess KA, Murtha AP, Jared H, Madianos PN, Moss K, et al. The oral conditions and pregnancy study: periodontal status of a cohort of pregnant women. Journal of periodontology. 2004;75(1):116-26.

10. Rio R, Azevedo Á, Simões-Silva L, Marinho J, Silva MJ, Sampaio-Maia B. The biochemistry of saliva throughout pregnancy. MedicalExpress. 2015;2(5).

11. Rivero ER-C, de Araújo LMA. Granuloma piogênico: uma análise clínico-histopatológica de 147 casos bucais. Revista da Faculdade de Odontologia-UPF. 1998;3(2).

12. Selvi UPG, Kamatchi D, Jeyashri S, Chanthinidevi A. Prevalence of Oral Lesions and Measurement of Salivary pH in the Different Trimesters of Pregnancy. INTERNATIONAL JOURNAL OF SCIENTIFIC STUDY. 2017;4(12):164-8.

13. Shulman J, Carpenter W. Prevalence and risk factors associated with geographic tongue among US adults. Oral diseases. 2006;12(4):381-6.

14. Thomaz ÉBAF, Alves CMC, Ribeiro CCC, Batista RFL, Simões VMF, Cavalli R, et al. Desfechos perinatais e alterações na cavidade bucal: coortes brasileiras de Ribeirão Preto e São Luís. Revista Brasileira de Epidemiologia. 2015;18:966-70.

15. Wandera M, Åstrøm AN, Okullo I, Tumwine JK. Determinants of periodontal health in pregnant women and association with infants’ anthropometric status: a prospective cohort study from Eastern Uganda. BMC pregnancy and childbirth. 2012;12(1):90.

16. Yun S, Lee JB, Kim SJ, Won Y, Lee SC. Recurrent geographical tongue and fissured tongue in

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4 CONCLUSÃO

Lesões em mucosa oral foram presentes em 1 a cada 10 gestantes, aproximadamente. Hiperplasia gengival foi a lesão mais prevalente. Estudos futuros devem levar em consideração metodologias homogêneas como o padrão de referência de critério diagnóstico e amostras com tamanho adequado podem melhorar a avaliação das lesões e a qualidade da evidência.

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REFERÊNCIAS