Introduction

Molar-Incisor Hypomineralization (MIH) is an enamel defect of systemic origin that affects from 1 to 4 permanent first molars and is frequently associated with permanent incisors.¹ Clinically, it presents as alterations in the translucency of enamel that produce well demarcated opacities, in shades of colors between white and brown, ranging in localization and severity.²

In many cases, molars with severe MIH have post-eruptive breakdown (PEB) due to reduction in hardness and high porosity of the enamel.^3,4 Hypomineralized teeth are more susceptible to biofilm accumulation, caries lesions and esthetic problems.^5-7 There are multiple treatment options for teeth affected by MIH, which ranges from preventive treatments, to the use of adhesive materials and the association between tooth extraction and orthodontic treatment.⁸

MIH is a public health problem that has the potential to cause severe suffering for children and their families. Disseminating information about this enamel defect is important for improving monitoring and the possibility of consistently performing early diagnosis.⁹

As a result, a significant increase in the number of research studies has been observed over the last few years, together with the exponential growth of publications about enamel defects, especially about MIH. For the purpose of evaluating and following up on scientific production worldwide, some analytical instruments have been used with the objective of determining a retrospective pattern of a topic and speculating about the direction of future research.¹⁰

Therefore, bibliometric studies may be considered a useful approach to describing a trend of development of a research field.¹¹ Determining the number of times an article has been cited by other authors is an important method for evaluating the scientific importance of that article.¹²

Although the number of citations does not really reflect the quality of an article, studies that are frequently cited may promote changes in clinical practice, trigger discussions and lead to new research in a specific area.¹³

Over the last few years, various bibliometric studies have been conducted to analyze the most cited articles in some areas of dentistry, such as periodontics, endodontics, orthodontics and pediatric dentistry.^14-17 However, to the best of the authors’ knowledge, an analysis of the most cited articles in the area of enamel defects has not been performed yet. This is why the objective of the present study was to identify the 100 most cited articles about MIH and analyze their characteristics.

Material and Methods

A search was performed using Web of Science (WOS), property of Clarivate Analytics, and included the publications in all databases (Web of Science Core Collection (WOS), Derwent Innovations Index (DIIDW), KCI-Korean Journal Database (KJD), Russian Science Citation Index (RSCI) and Scientific Electronic Library Online Citation Index (SciELO)) in the category of "Dentistry, oral surgery, and medicine”, without restriction on the period of time, language, type of article or journal.

Data were collected on May 31, 2021 using the topic search (TS) command and the following search strategy: (enamel abnormalit* OR enamel hypoplasia OR enamel permeability OR hypoplasia enamel OR mottled enamel OR enamel hypomineralization OR enamel hypomineralisation OR enamel defect OR enamel agenesis OR enamel opacit* OR hypomineralized molar OR hypomineralised molar OR opaque spot OR cheese molar OR hypoplastic enamel OR tooth hypomineralization OR tooth hypomineralisation OR hypomineralization OR hypomineralisation).

Two authors independently evaluated the articles found and any disagreement about the articles was resolved by consensus after a third author of the review had been consulted. The evaluation ceased on reaching the one hundredth most cited article. Furthermore, a search was made in the Scopus database, to compare the total number of citations of the selected articles.

Afterwards, the final list was ordered by the number of citations in decreasing order, and the following data were extracted from each article: number of citations, mean number of citations per year, title, authors, country (based on the first author’s affiliation), continent, year of publication, impact factor of scientific periodicals in which the studies were published, study design (cross-sectional, experimental, observational, longitudinal, diagnostic, systematic review, review of the literature, clinical study and case series), thematic field, proponent institutions and keywords). Based on the thematic field, the articles were grouped under the following topics of interest: dental caries, diagnosis, epidemiology, etiology, hypersensitivity, esthetic perception, morphological properties, quality of life and treatment.

The data extracted were organized in an Excel spreadsheet (Microsoft Office for Mac 2011 package). Descriptive statistics were prepared for the information collected by using Jamovi v.1.2 (The jamovi project, Sydney, Australia). To develop the keyword collaboration and co-occurrence network maps, the VOSviewer software was used.

Results

The searches conducted in Web of Science and Scopus led to identification of a total of 10,196 and 8,928 articles, respectively. The 100 most cited articles relative to MIH are presented in Table 1, listed in decreasing order according to the number of citations received and the number of citations per year. In general, the most cited articles received 5,354 citations and 138.92 citations per year. The article with the highest number of citations was “Weerheijm KL, Jalevik B, Alaluusua S.

Molar incisor hypomineralization. Caries Res 2001; 35(5):390-1”, was cited 303 times (mean: 14.48 citations / year). The majority of studies were published in the 2010s (58%), followed by the 2000s (38%) (Figure 1).

The most cited articles were published in 32 journals and 40% were published in specific journals of pediatric dentistry: International Journal of Paediatric Dentistry (26), European Archives of Paediatric Dentistry (6), Pediatric Dentistry (4), Journal of Dentistry for Children (2) and European Journal of Paediatric Dentistry (2). The impact factor (IF) of the journals ranged from 0.339 to 10.317. The journal with the highest IF (10.317) was Biomaterials that published one article.

Regarding thematic fields, the majority of research was related to epidemiology (35%), followed by Etiology (25%), Morphological Properties (15%), Treatment (9%), Diagnosis (8%), Dental Caries (6%), Esthetic Perception (3%), Hypersensitivity (2%) and Quality of Life (1%). Categorization of articles in terms of MIH’s etiology and management is presented in Figures 2 and 3, respectively.

Europe (43%) and Oceania (27%) were the continents with the greatest contribution to the list of the most cited articles,

followed by South America (15%) and Asia (10%). Australia was responsible for the majority of the papers included (23%), followed by Brazil (14%), Sweden (11%) and Germany (8%). Europe had the highest number of countries (46.15%) with the published articles receiving high levels of citation (Figure 4). The most cited authors (irrespective of being corresponding or co- authors) were Manton, D. J. (881 citations), Jalevik, B. (749 citations), Kilpatrick, N.M. (599 citations), Alaluusua, S. (595 citations), Weerheijm, K.L. (585 citations), Noren, J. G. (451 citations), Swain, M.V. (412 citations), Crombie, F.A. (354 citations), Jeremias, F. (341 citations) and Ghanim, A. M. (304 citations) (Table 2). Sixteen institutions contributed two or more studies included in the ranking, with the University of Melbourne in Australia presenting most

collaborations (17%), followed by the São Paulo State University - UNESP in Brazil, and the University of Gothenburg in Sweden, both with five publications each (Figure 5).

Evaluation of all the author keywords and KeyWords Plus indicated that the most popular terms were “prevalence” (n = 44), “teeth” (n = 39), “children” (n = 34) and “enamel” (n = 31) (Figure 6).

With respect to study design, the majority of the studies were of the cross-sectional type (39%), followed by experimental studies (24%), observational studies (14%), systematic reviews (9%), literature reviews (6%), longitudinal studies (4%), diagnostic

studies (2%), clinical studies (1%) and case series (1%), as described in Table 3.

Discussion

The objective of the present study was to identify the 100 most cited articles about MIH and analyze their characteristics. To the best of the authors’ knowledge, this is the first study to explore research in the area of enamel defects. The searches conducted in Web of Science and Scopus led to identification of a total of 10,196 and 8,928 articles, respectively. Our search covered a broad spectrum of enamel defects through the use of diverse keywords. This choice was influenced by the fact that the formal designation of MIH was only established in 2001,¹ Prior to which various nomenclatures were employed to describe the same clinical condition. The evolution of terminology, along with ongoing disagreements among researchers in distinguishing hypomineralizations from hypoplasias and other enamel defects, informed our selection of keywords. Nonetheless, a careful analysis of identified articles was carried out, resulting in the exclusion of those not directly relevant to MIH. The records returned by the Scopus and Web of Science databases varied considerably. The coverage of Web of Science dated back to 1900, while the coverage of articles prior to 1996 was more limited in Scopus.^18,19 For this reason, the list of the 100 main articles was based on WOS.

Our study identified 10 articles that obtained over 100 citations. According to Heldwein, Rhoden and Morgentaler,²⁰ studies that receive 100 or more citations may be considered classics, because they represent historical points of reference in the development of a specific area. Of the 100 articles, 39 were of the cross-sectional type, 24 experimental and 14 observational. These types of study are more frequently used in the areas of medicine, due to being more easily conducted and have greater cost-benefit.²¹

The articles were published between the years 1982 and 2019, however MIH was first described only in 2001. Prior to this date, four articles were identified that used old terminologies for describing this condition (“Cheese Molars” and “'non- fluoride hypomineralization”). In the year 2001, seven articles were published, including the study that led the ranking of citations, and that was responsible for the contemporary denomination of MIH.¹ Naturally, it was to be expected that the pioneer study would be cited with high frequency by subsequent studies. As from this period, there was a growing number of publications in the area, especially in the year 2013, when of eleven published studies, 73% approached the etiological aspects and relations of MIH with dental caries.

Indeed, to date, the etiology of MIH is still unclear, but it is believed to be multifactorial.²² For this reason, several papers have been published to describe factors associated with this enamel defect. Amongst the various etiological hypotheses mentioned in the most cited papers, risk factors causing disturbances have included medication use (e.g., antibiotics) and childhood illnesses ^23,24 as the most published subject. However, it is difficult to differentiate whether the MIH is caused by the childhood disease or as a result of how the disease is managed (e.g., the use of antibiotics).²⁵ More recently, a genetic predisposition in conjunction with one or several other epigenetic factors has also been proposed.^26-28 This was expected, given that the entire process of dental enamel formation is under genetic control, and suggests that genetic causes could be at least partly responsible for MIH development.²⁶

It was found that several treatments have been reported. Management of MIH can be complicated, and often requires consideration of several individual and tooth-specific factors before making a decision.²⁹ Most of papers of the list regarding treatment includes preventive procedures indicated only in cases where there is no structural tooth loss, or else conservative or invasive restorations with removal of the affected area.

Bibliometric studies in the area of dentistry have pointed out the United States and consequently, American authors as being leaders in the rankings of studies with high levels of citation ³⁰,³¹. However, in the present study, countries such as Australia (23%), Brazil (14%) and Sweden (11%), were identified as being the pioneers in researches about MIH. The high prevalence of MIH found in these regions suggested that there was greater concern about conducting in-depth research.^3,32,33

Among the authors, Ghanim, A. M. is the only collaborator to appear six times as the first author among the most cited articles, however, she is ranked tenth in the number of citations (304 citations). Although Manton, D. J. is not the first author in any of the articles, but this author has a higher number of studies in the ranking (18%) and the highest number of citations (881). Alaluusua, S. was ranked the tenth author in quantity of articles included (four), however, he was ranked fourth in the number of citations (595). There are various factors that may influence the quantity of citations of an article. Therefore, a high quantity of studies published by one and the same author may not exhibit a high rate of citations.³⁴

The University of Melbourne, the University of Gothenburg and the São Paulo State University - UNESP were the institutions that produced the most studies about MIH. This is because these universities are located in the continents that most conduct researches about the topic, particularly due to the high prevalence of cases of this condition. These institutions contemplated 27% of the total number of articles and are affiliated with 93.5% of the ten most cited authors.

The studies were published in 32 different journals, the majority (40%) in specific journals of pediatric dentistry. Although the diagnosis of MIH may be more easily made by professionals in pediatric dentistry, by virtue of the time of eruption of the molar, it is interesting to note the low quantity of articles in other areas of dentistry, such as oral biology (3%) and cosmetic dentistry (6%) that could make a significant contribution to research with an approach to the etiological factors and treatments.

Analyzing the keyword co-occurrence network is a tool for mapping the domain of research in a specific field, by examining the connections among keywords. According to Figure 4, those in the largest and most centrally localized nodes were filled by terms such as “prevalence” “teeth” “children” and “enamel”. The keyword “prevalence” had a significant weight, probably due to the increase in studies for determining the prevalence of MIH in the world population. This result had been expected seeing that 35% of the studies included were considered to be of the epidemiological type.

The 100 most cited articles showed heterogeneity in their themes and study designs, in spite of the high prevalence of cross-sectional studies (39%). This type of study is frequently conducted in the area of health because it is accessible and fast to conduct when evaluating the prevalence of health problems.³⁵ Longitudinal studies represented only 4% of all the articles in the ranking. These studies are useful for evaluating the cause-and-effect relationships of a certain disease, in addition to the risk factors and development of some type of alteration. However, a longer time and more financial resources are required to conduct them.³⁶ It is important to point out that so far, no etiological factor has been directly established in the investigation of the relations of cause and effect of MIH. Further high-quality longitudinal studies are suggested.

As is the case with other bibliometric studies, our analysis had some limitations. Firstly, a possible bias may be due to self- citation since the Web of Science does not perform automatic exclusion and this factor was not controlled in our study. Secondly, the count of citations does not directly reflect the quality of a paper but allows a quantitative evaluation of the scientific impact of an article. However, there is a risk of bias related to the time of publication, by means of which some old publications had more time to accumulate citations.

Conclusion

To the best of the author’s knowledge, this is the first bibliometric study about the 100 most cited articles about MIH. There was predominance of cross-sectional studies and prevalence rates. The majority of the articles were published as from the decade of 2010, with Australia being the country with the most prolific production. The 100 most cited studies were published in a total of 32 journals, and the Europe was the continent with the greatest contribution to the list. Evaluation of the 100 most cited articles in the area of enamel defects allowed better understanding of the world scenario with reference to MIH.