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Luisa Meier

5

th

year, group 11

Molar- incisor hypomineralization and its treatment

peculiarities in children- a systematic review

Master’s Thesis

Supervisor

DMD Sandra Petrauskienė

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LITHUANIAN UNIVERSITY OF HEALTH SCIENCES MEDICAL ACADEMY

FACULTY OF ODONTOLOGY

CLINIC FOR PREVENTIVE AND PEDIATRIC DENTISTRY

MOLAR- INCISOR HYPOMINERLIZATION AND ITS TREATMENT PECULIARITIES IN CHILDREN- A SYSTEMATIC REVIEW

Master’s Thesis

The thesis was done

by student ... Supervisor ...

(signature) (signature)

... ...

(name surname, year, group) (degree, name surname)

... 20…. ... 20…. (day/month) (day/month) Kaunas, 2019

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EVALUATION TABLE OF THE MASTER’S THESIS

OF THE TYPE OF SYSTEMIC REVIEW OF SCIENTIFIC LITERATURE Evaluation: ... Reviewer: ...

(scientific degree. name and surname)

Reviewing date: ...

No. MT parts MT evaluation aspects

Compliance with MT requirements and evaluation Yes Partially No 1 Summary (0.5 point)

Is summary informative and in compliance with the

thesis content and requirements? 0.3 0.1 0

2 Are keywords in compliance with the thesis essence? 0.2 0.1 0 3

Introduc-tion, aim and tasks (1 point)

Are the novelty, relevance and significance of the

work justified in the introduction of the thesis? 0.4 0.2 0 4 Are the problem, hypothesis, aim and tasks formed clearly and properly? 0.4 0.2 0

5 Are the aim and tasks interrelated? 0.2 0.1 0

6 Selection criteria of the studies, search methods and strategy (3.4 points)

Is the protocol of systemic review present? 0.6 0.3 0 7

Were the eligibility criteria of articles for the selected protocol determined (e.g., year, language, publication condition, etc.)

0.4 0.2 0

8

Are all the information sources (databases with dates of coverage, contact with study authors to identify additional studies) described and is the last search day indicated?

0.2 0.1 0

9

Is the electronic search strategy described in such a way that it could be repeated (year of search, the last search day; keywords and their combinations; number of found and selected articles according to the combinations of keywords)?

0.4 0.1 0

10

Is the selection process of studies (screening, eligibility, included in systemic review or, if applicable, included in the meta-analysis) described?

0.4 0.2 0

11

Is the data extraction method from the articles (types of investigations, participants, interventions, analysed factors, indexes) described?

0.4 0.2 0

12

Are all the variables (for which data were sought and any assumptions and simplifications made) listed and defined?

0.4 0.2 0

13

Are the methods, which were used to evaluate the risk of bias of individual studies and how this information is to be used in data synthesis, described?

0.2 0.1 0

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15 Systemiza-tion and analysis of data (2.2 points)

Is the number of studies screened: included upon assessment for eligibility and excluded upon giving

the reasons in each stage of exclusion presented? 0.6 0.3 0 16

Are the characteristics of studies presented in the included articles, according to which the data were extracted (e.g., study size, follow-up period, type of respondents) presented?

0.6 0.3 0

17

Are the evaluations of beneficial or harmful outcomes for each study presented? (a) simple summary data for each intervention group; b) effect estimates and confidence intervals)

0.4 0.2 0

18

Are the extracted and systemized data from studies presented in the tables according to individual tasks?

0.6 0.3 0

19

Discussion (1.4 points)

Are the main findings summarized and is their

relevance indicated? 0.4 0.2 0

20 Are the limitations of the performed systemic

review discussed? 0.4 0.2 0

21 Does author present the interpretation of the

results? 0.4 0.2 0

22

Conclusions (0.5 points)

Do the conclusions reflect the topic, aim and tasks

of the Master’s thesis? 0.2 0.1 0

23 Are the conclusions based on the analysed material? 0.2 0.1 0

24 Are the conclusions clear and laconic? 0.1 0.1 0

25

References (1 point)

Is the references list formed according to the

requirements? 0.4 0.2 0

26 Are the links of the references to the text correct? Are the literature sources cited correctly and precisely?

0.2 0.1 0

27 Is the scientific level of references suitable for Master’s thesis? 0.2 0.1 0 28 Do the cited sources not older than 10 years old form at least 70% of sources, and the not older than

5 years – at least 40%?

0.2 0.1 0

Additional sections, which may increase the collected number of points

29 Annexes Do the presented annexes help to understand the analysed topic? +0.2 +0.1 0 30

Practical

recommen-dations

Are the practical recommendations suggested and

are they related to the received results? +0.4 +0.2 0 31

Were additional methods of data analysis and their results used and described (sensitivity analyses,

meta-regression)? +1 +0.5 0

32

Was meta-analysis applied? Are the selected statistical methods indicated? Are the results of

each meta-analysis presented? +2 +1 0

General requirements, non-compliance with which reduce the number of points 33

General

require-ments

Is the thesis volume sufficient (excluding annexes)? 15-20 pages (-2 points) <15 pages (-5 points)

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34 Is the thesis volume increased artificially? -2 points -1 point

35 Does the thesis structure satisfy the requirements of Master’s thesis? -1 point points -2 36 Is the thesis written in correct language, scientifically, logically and laconically? -0.5 point points -1 37 Are there any grammatical, style or computer literacy-related mistakes? -2 points -1 points

38 Is text consistent, integral, and are the volumes of its structural parts balanced? -0.2 point points -0.5

39 Amount of plagiarism in the thesis. >20%

(not evaluated) 40

Is the content (names of sections and sub-sections and enumeration of pages) in compliance with the thesis structure and aims?

-0.2 point -0.5 points

41

Are the names of the thesis parts in compliance with the text? Are the titles of sections and sub-sections distinguished logically and correctly?

-0.2 point points -0.5 42 Are there explanations of the key terms and abbreviations (if needed)? -0.2 point points -0.5 43

Is the quality of the thesis typography (quality of printing, visual aids, binding) good?

-0.2 point points -0.5 *In total (maximum 10 points):

*Remark: the amount of collected points may exceed 10 points.

Reviewer’s comments: ___________________________________________________________ ______________________________________________________________________________ ______________________________________________________________________________ ______________________________________________________________________________ ______________________________________________________________________________ ______________________________________________________________________________ ______________________________________________________________________________ ______________________________________________________________________________ ______________________________________________________________________________ ______________________________________________________________________________ _________________________________________ ___________________________

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TABLE OF CONTENTS

SUMMARY...8

INTRODUCTION...9

1. SELECTION CRITERIA OF THE STUDIES...11

1.1 Literature search strategy ...11

1.2 Inclusion and exclusion criteria...11

2. SYSTEMATIZATION...15 3. DISCUSSION...18 4. CONCLUSIONS...20 5. REFERENCES...25 ANNEXES...28

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ABBREVIATIONS:

MIH- Molar- incisor hypomineralization FPM- First permanent molar

EAPD- European Academy of Paediatric Dentistry SCASS- Schiff Cold Air Sensitivity Scale

WBFS- Wong-Baker Faces Scale LA- Local anesthetic

IO- Intraosseous anesthesia

CPP- ACP- Casein phosphopeptide-amorphous calcium phosphate TCP- Tricalcium phosphate

QLF- Quantitative Light-Induced Fluorescence LF- Laser- induced fluorescence

GIC- Glass Ionomer Cement

USPHS- United States Public Health Service ART- Atraumatic restorative treatment OH- Oral hygiene

SE- Standard error Gr- Group

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SUMMARY

Objective: Aim of the systematic review was to search and select the current publications related to the selected topic. Furthermore to analyze the selected studies regarding their study outcome and assess which diagnostic methods are the most frequently used for the severity of MIH. The final goal was to establish a practical treatment guide.

Material and method: A systematic review was carried out to identify relevant studies reporting data on various treatments of MIH carried out in pediatric dentistry. The keywords Molar- incisor hypomineralization, enamel hypomineralization, dental treatment, and their combinations were used during the search. The search was performed through “PubMed”, as well as “MEDLINE”,

“Cochrane library”, and “Embase”. Articles were restricted to English and German language, published from 2009 to 2019.

Results: A total of 537 permanent teeth were observed in selected studies. In 7 studies treatment procedures were done for first permament molars, in 1 study only for incisors and 1 study included both first permanent morals and incisors. 5 studies included mild and severe MIH in their studies. 2 studies were including only mild or severe MIH, respectively.

Conclusion: Lower physical properties, combined with neglected OH and difficulties achieving LA are findings in MIH teeth. However, preventive and restorative treatment is possible with a not significantly lower success rate than for healthy teeth. Effective treatments identified were arginine paste, fluoride varnishes, GIC restoration, and Glass hybrid restoration. IO administration was found to be most effective as LA.

Clinical significance: Because the number of MIH patients seeking help in dental practices is rising, it is extremely important to review the literature regarding MIH treatment.

Keywords

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INTRODUCTION

There is a challenge on the rise for pediatric dentists, called molar- incisor hypomineralization (MIH). In 2001 Weerheijm et al. suggested that term, instead of the wide range of terms used previously to describe the condition, such as “Cheese Molars“, “idiopathic enamel

hypomineralisation in the first permanent molars“, “non- fluoride hypomineralisation in FPM“, and “hypomineralised first permanent molars“, all in year 2000 [1].

Reported prevalence rates of MIH vary greatly from 2.4 to 40.2% [2, 3, 4].

Clinically MIH presents as hypomineralization of at least one FPM, the central incisors may or may not be involved. Affected teeth show clearly demarcated opacities that are white to yellow/brown on their buccal or occlusal surfaces [5]. A connection has been found between the darkness of the colour of opacity and severity of MIH [6]. The enamel opacities have a degree of porosity, depending on severity. In severe cases, the enamel may break under masticatory forces and leave exposed, caries- prone dentine.

Further clinical signs of MIH are atypical restorations of molars or incisors. Those restorations are not conforming with the present caries picture, and in molars the fillings are often extending to buccal or oral smooth surfaces [7]. Moreover, tooth sensitivity may be reported, ranging from mild sensitivity to so severe, that even tooth brushing or breathing cold air can cause a shooting pain [8]. Enamel is the hardest tissue in the body. Unlike dentine, cementum, and the dental pulp, which are of ectomesenchymal origin, the enamel is of ectodermal origin. Tooth formation is taking place in three stages: the bud, cap and bell stage. The tooth buds for the permanent teeth develop at different weeks of fetal development. Only the buds of the second and third permanent molars appear only at about four months or five years after birth respectively [9]. The calcification of the first permanent molars begins at birth, of central incisors at three to four months [10].

The etiology of MIH is still unknown, but the cause is thought to be found in the period of calcification, described previously. Some conducted studies link MIH to prenatal factors (like illness during pregnancy, maternal smoking), perinatal factors (like low birth weight, caesarian delivery), as well as early childhood illnesses (i.e. asthma, pneumonia) [11]. A recently discovered health threat associated with MIH is the perinatal exposure to Bisphenol A (BPA), an organic synthetic compound, primarily used to produce plastics [12].

Present clinical signs and symptoms often make early extensive treatment necessary. Teeth affected by MIH need nearly 10 times more treatment than teeth without MIH [13]. The inferior quality of the hypomineralized enamel presents specific treatment challenges. Porous enamel, exposed dentine, and neglected OH, due to pain while brushing, may cause rapidly developing caries [14].

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Often a subclinical inflammation of the pulp, caused by the porosity of enamel, can make it difficult to achieve local analgesia [13].

Restoration attempts face a worse adhesion on the soft, hypomineralized enamel. [14]. MIH enamel shows increased amounts of proteins like serum albumin, type I collagen, ameloblastin,

a1-antitrypsin, and antithrombin III, which were found to inhibit the growth of hydroxyapatite crystals and enzymatic activity during enamel maturation, resulting in an overall reduction of minerals in MIH enamel [15,16]. Histologically less distinct prism sheaths and a lack of arrangement of the enamel crystals lower mechanical properties [17,18].

Aggravating this situation is the young age of the patients, which causes considerable demands in behavior management [13].

Treatments of MIH include preventive measures, symptom control for hypersensitivity, and restorative treatment. Preventive optionsare sealants for posterior teeth. Varnishes and

desensitizing pastes, such as pro- arginine pastes, are used against hypersensitivity. Restoration options range from GIC, glass hybrid restorative systems, composite fillings, to metal crowns. In severe cases, extraction might be the treatment of choice [19].

Aim: To analyze the publications about treatment related to MIH, to assess its effectiveness and to organize the latest treatment modalities of MIH according to severity.

Objectives:

1. To search and select the publications according to prepared inclusion and exclusion criteria for systematization and analysis of the topic.

2. To analyze the selected studies regarding the treatment outcomes.

3. To assess which diagnostic method(s) are the most used for the severity of MIH respectively. 4. To create a treatment practical guideline.

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1. SELECTION CRITERIA OF THE STUDIES 1.1 Literature search strategy

Following the PRISMA guidelines, publicated articles included in this systematic review were selected through PUBMED, Embase, Cochrane library, as well as MEDLINE. Molar- incisor hypomineralization/ enamel hypomineralization/ dental treatment and the combination of the terms were used as keywords for the search.

The comprehensive search was restricted to articles in English and German language, published from 2009 to 2019. One investigator carried out the search, selection, and evaluation of the articles. 36 articles were found. Articles, which were not fully accessible without purchasing and

duplications, were excluded. 22 articles were analyzed and 9 articles with the theme of this review qualified regarding to PICOS criteria (Annex 1).

Follow up period was not a mandatory aspect. 1.2 Inclusion and exclusion criteria

Inclusion criteria for the selection were the following: • Publications written in English and German language • Articles published < 10 years ago

• Studies performed in vivo and on humans

• Studies performed on participants younger than 18 years • Full texts of articles

• Preventive or treatment interventions done on molars and/or incisors with MIH Exclusion criteria:

• Non-full articles or inaccessible unless purchased • Articles published > 10 years ago

• Studies performed in vitro or on animals • Participants older than 18 years old

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PICOS (eligibility criteria)

Participants younger than 18 years with at least one hypomineralized PFM or incisor were included. The gender did not play a role.

MIH ofteeth was examined and diagnosed regarding the EAPD (European Academy of Paediatric Dentistry) criteria. The EAPD criteria include demarcated opacities (<1mm were not included in the analysis), enamel disintegration, tooth sensitivity, atypical restorations.

The MIH severity was also determined according to the EAPD (Table 1), except for one study by Dixit et al., which used the Wetzel and Reckel scale (Table 2) [20].

Table 1. MIH severity according to EAPD.

Table 2. MIH severity according to Wetzel and Reckel scale (1991)

Measurement techniques were the following: visual/tactile examination with sensitivity and pain scales, laser-induced fluorescence, quantitative light-induced fluorescence, time for administration, onset and required repeat.

SCASS (Schiff Cold Air Sensitivity Scale) response to air blast stimuli applied for 1 min (scores: 0= No respond to stimulus; 1= No respond to stimulus, but stimulus considered as painful; 2= subject responds to air stimulus and moves from stimulus; 3= subject responds to air stimulus, moves from stimulus and requests immediate discontinuation of the stimulus).

Mild Severe

Study included [20], [23], [24], [25], [26], [27], [28] [20], [23], [24], [25], [28], [29], [30] Clinical

findings

Demarcated enamel opacities

No enamel break- down Enamel breakdown, caries Complains

(History findings)

Occasional sensitivity to external stimulus e.g. air/water but not brushing

Persistent/spontaneous

hypersensitivity, affecting function Only mild aesthetic concerns on

discoloration of incisors

Strong aesthetic concerns

Severity grade Clinical findings

A Mild opacities

B Significant discoloration with low loss of substance C Mineralization disturbances with considerable defects

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WBFS (Wong-Baker Faces Scale) response to scratching on the surface of MIH- affected tooth with explorer: according to pain intensity from 0 (no pain) to 10 (hurts worst).

LF measures the fluorescence level present because of bacterial products, while QLF detects demineralized enamel [21].

Treatments that have been done were preventive treatments, symptom control, as well as restorative measures.

The success rate was defined in various ways, such as a decrease in stimuli response, decreased LF and QLF values, less time for LA administration, onset, as well as unnecessary repeat.

Success of restorative fillings was defined according to USPHS criteria, which focuses on anatomical form, marginal adaptation, surface texture, marginal discoloration, retention, as well as secondary caries.

ART restoration was judged with respective codes, ranging from 0 (present, satisfactory restoration), over 5 (present, overextension of approximal margin of 0.5 mm or more) to 9 (unable to diagnose.

An overview of the quality assessment can be found in table 3. Only 4 of the 9 included studies clearly stated that an efficient amount of participants have been included. With one exception however, all described the treatments that have been done clearly. Also, the p- value was stated in 8 out of 9 studies. Statistics were described in 7 studies. One study failed to mention the statistics, while one was unclear.

Table 3. Quality assessment of articles included in the analysis

Nr. Publication author, year Sufficient amount of participants Clear treatment explanation p- values Statistics described 1 Bekes et al. (2016) + + + + 2 Biondi et al. (2017) ? + + ? 3 Dixit et al. (2018) + - + + 4 Fragelli et al. (2017) + + + + 5 Fragelli et al. (2015) ? + + + 6 Grossi et al. (2018) ? + - + 7 Lygidakis et al. (2009) ? + + - 8 Restrepo et al. (2016) + + + + 9 Souza et al. (2016) ? + + +

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Figure 1 illustrates by a flow chart the process of filtering (PRISMA flow diagram)

Records identified through database searching (PubMed) (n =36) Sc re en ing In cl u d ed El ig ib il it y Id en ti fi cat ion

Additional records identified through other sources (MEDLINE, Cochrane library, Embase)

(n =41)

Records after duplicates removed (n =23)

Records screened (n =23)

Records excluded (n =8)

Full-text articles assessed for eligibility

(n =15)

Full-text articles excluded, with reasons (n =6) Studies included in qualitative synthesis (n =9) Studies included in quantitative synthesis (meta-analysis) (n =0)

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2. SYSTEMATISATION AND ANALYSIS OF DATA

The main findings of this systematic review are presented in Table 4. In total 9 published from 2009 to 2019 were analyzed. Overall, 8 of 9 studies had a control group (teeth not affected by MIH). All studies were performed in vivo, with the sample size of participants ranging from 18 to 55. The age of patients varied from 6 to 17 years old. Gender ratio has not been mentioned.

The sample size of teeth varied from 41 to 94. A total of 537 permanent teeth were observed in all studies.

In 7 studies treatment procedures were done for first permanent molars, in 1 study- only for incisors and 1 study included both first permanent morals and incisors. No comparative measures have been made between mandibular and maxillary teeth.

5 studies included mild and severe MIH in their studies. 2 studies included only mild or severe MIH, respectively.

Follow-ups were done in 8 studies, ranging from 1 month to 4-year period. The average follow-up period was 14 months. One study examining local anaesthesia did not require a follow-up period, due to its study nature.

Treatment peculiarities

Treatment peculiarities for teeth with MIH depend on several aspects, such as severity level, patients complains and restorative treatment need (Figure 2).

Desensitizing toothpastes and self-adjunct products

Hypersensitivity is a frequent complaint among patients with MIH [22]. Bekes et al. tested the efficacy of desensitizing products containing 8% arginine and calcium carbonate on the

hypersensitivity of mildly and severely MIH affected molars [23]. After professional applications with an arginine paste and implementing a home-based program, airblast and tactile tests showed a reduction of sensitivity after 8 weeks (p<0.001) (Table 3).

Biondi et al., and Restrepo et al. used 1450 ppm and 1000 ppm fluoridated toothpaste in addition to their studied treatment.

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Varnish

Two of the included studies [24, 25] were evaluating the effect of varnish (Duraphat) on

mineralization. Moreover, a home-based regimen was given in both studies; and the main difference was that Restrepo et al. adviced to use toothpaste with 1450ppm of fluoride and Biondi et al.

recommended toothpaste 1000ppm of fluoride. In addition, Biondi at al. compared effectiveness of the other two materials CPP- ACP (Recaldent) and 5% sodium fluoride varnish containing TCP (Clinpro) for other groups as well. Finally, LF measures showed no significant improvement in Respero et al. study (p>0.05), however, Biondi et al. stated that Duraphat was the most effective in moderate lesions (p<0.000005), Clinpro in the mild lesion (p<0.01).

3 more studies (Fragelli et al., Fragelli et al., Souza et al.) included in this review were using Duraphat as a pretreatment for sealant application or restoration. However, no focus has been paid to its effect.

Sealant

Two studies [26, 27] analyzed the success of preventive treatment with sealant application. In one study (Fragelli et al.) success rate was compared between molars with MIH and molars without MIH. Although the pretreatment procedure with varnish application was perform for molars with MIH, the success rate was higher in the control group than in study group (72% vs. 62.2%) after 18 months (p>0.05). Meanwhile, another study (Lygidakis et al) was focused on different adhesive systems. Results revealed that sealants placed with a prior application of a 2- step etch and rinse single- bottle adhesive had greater retention than placement without adhesive material after 48 months (p>0.001).

Local anaesthesia

Effect of local anesthesia (infiltration and intraosseous) of MIH teeth was assessed in one study [20]. Measurements were taken for the time of administration, the onset of LA, as well as required repeat. Intraosseous local anesthetic technique required significantly more time (63.22±21.9), compared to infiltration (37.4±10.4) (p<0.004). However, the onset of local anesthesia was faster in intraosseous anesthesia (8±11.5) than in infiltration technique (58.85±6.8) (p<0.0001). In addition, the infiltration technique needed to be repeated significantly more often than intraosseous

anesthesia (44.4% vs. 7.4%) (p<0.004). Restorations

3 studies concerning restorations of MIH teeth were included [28,29,30]. One study focused on measuring the success rate of GIC (Fragelli et al), the second of Glass- hybrid restoration (Grossi),

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and the last one (De Souza) of composite resin restorations, comparing two adhesive systems, respectively. Fragelli et al. combined 4 weekly applications of 5% fluoride varnish (Duraphat), OH instructions and the restorative treatment (caries lesions were removed and MIH affected areas were untouched) with GIC for first permanent molars with both mild and severe MIH. A success rate was 78% of the GIC restorations according to USPHS criteria

Grossi et al. used ART technique for caries removal and placed a glass hybrid restoration in

severely affected first permanent molars. A success rate was 98.3%, according to the ART criterion [29].

De Souza et al. were focussing on direct composite resin restorations and two different adhesive systems: a self- etching adhesive, and a total-etch adhesive [30]. Moreover, Duraphat was applied weekly for one month, and temporary GIC restorations were performed. After 2 months the teeth were randomly divided into a SEA and TEA group and treated respectively. The success rate was 68.4% for the SEA, and 54.6% for the TEA group (p>0.304).

This systematic review relieved higher succcess rate when GIC or Glass- hybrid restoration were used as permanent filling material. However, this could be due to a shorter follow up period in the treatments with those materials respectively.

Figure 2. Treatment guidelines

Prevention Varnish (Clinpro) Sealant

Varnish (Duraphat) Sealant

Symptom Control

ProArgin treatment ProArgin treatment Restoration Composite resin restoration GIC restoration

Composite resin restoration Glass hybrid restoration Preformed metal crown Exodontia

Anaesthesia IO IO

Demarcated enamel opacities of FPM or incisors present?

Enamel breakdown present?

no yes

Occasional sensitivity to external stimulus +

Mild aesthetic concerns

Persistent/ spontaneous hypersensitivity +

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3. DISCUSSION

Despite the growing numbers of MIH, research about its treatment is still limited. Most of the articles found about MIH are concerned with its etiology.

Two things in the included studies have been found to be consistent. The EAPD index was the exclusive index in the diagnostics of mild and severe MIH. It was introduced in March 2003 by the EAPD board. Previously used, the relevant index was the developmental defects of enamel index (DDE), reported by the FDI (World dental federation) working group in 1992. The DDE focuses on demarcated or diffuse opacities while ignoring hypersensitivity [31].

However, in 2017 a new index, the Würzburg index, has been established by international representatives from universities from Austria, Germany, and Switzerland. This index aims to be more specific about the extent of the found lesions. Thus creating a more detailed diagnosis and individual treatment planning. It was created to be used in epidemiological screening procedures for assessing MIH treatment needs, as well as the handling of patients in the dental practice. Thus, the use of that index would help in the understanding of the diversity in the severity of MIH. Furthermore, more comprehensive diagnostics and individual treatment planning became easier [32].

Secondly, all included studies were treating non- operatively. Further research needs to be done in all treatment options of MIH, with more attention being paid to different results in different MIH severities.

The early diagnosis and treatment of MIH is crucial to provide adequate treatment and to prevent negative side- effects that might be a consequence. The more porous enamel disintegrates

continuously with subsequent caries and hypersensitivity.

Not to be underestimated is also the psychological effect of MIH on children. MIH affected incisors are mainly found in the upper jaw, in an aesthetic sensitive area [33]. Some questionaires have given to schoolchildren in Brazil, to study the psychosocial impact of MIH [34, 35]. Those studies showed that it is having a negative effect on the children’s oral self- perception, as well as Oral Health-Related Quality of life (OHRQoL) [34]. Children with severe MIH were discontent about their teeth color, smiled less, and had problems interacting with their peers.

Hypersensitivities, frequent and time- consuming appointments at the dentist, and difficulties to achieve LA might cause dental fear and anxiety.

Besides those concerns, MIH is also causing a large financial impact upon patients, their parents, and society [36].

A variety of treatment options have been presented in this literature review. A practical guide for the dental practice, summarizing the results of this review, can be found as figure 2. After the

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general diagnosis of MIH, followed by its severity determination, treatment options are given according to complaints.

The numbers of children affected by MIH is one the rise. In Sweden, every fifth child is diagnosed with MIH [37], in Denmark hypomineralised defects of FPM are more found than occlusal caries [38].

A future goal should be further research in the field of MIH treatment, with the final goal of creating a detailed treatment guide for dental practitioners.

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4. CONCLUSIONS

To conclude, it can be said that the treatment of MIH is a challenge for the dentist. Lower physical properties, combined with neglected OH and negative associations of the child with dental

treatment as a result of difficulties achieving LA, are the main disruptive factors in achieving a mutually satisfactory and durable treatment.

However, collecting and analyzing studies included in his literature review has shown that preventive and restorative treatment of MIH affected teeth is possible with a not significantly worse outcome than for healthy teeth.

Further studies are necessary to meet the need of the rising number of MIH patients. Furthermore, it is in the interest of the community to improve treatment guidelines, as expenses caused by MIH treatment are not only a burden for private persons and their family but also healthcare funds. Additionally it is desirable to design future studies in a way that makes a more detailed breakdown of different MIH severities.

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Table 4. Studies included in the systematic review for the treatment of MIH Author/

Year/ Country

Study type Samp le (patie nts/ teeth) Age (year) MIH Index Treatment (dental procedure)

Dental materials Follow-up in months Measurements Result 1 Bekes et al. (2016) Austria Clinical trial 19/ 56 6-14 EAPD 1. Professional application of an arginine pastea (for 3s

2x) 2. home- based programb (8 wk) Elmex Sensitive Professional desensitizing pastea Elmex Sensitive Professional toothbrush and toothpastec Elmex Sensitive Professional mouthwashb

2 SCASS(estimates on log-adds scale): -6.8; SEe= 0.76 (p<0.001)

WBFS(estimates on log-adds scale): -2.91; SE= 0.53 (p<0.001)

This combined ProArgin treatment provided significant relief from hypersensitivity; maintenance of relief for 2 months (p<0.001) 2 Biondi et al. (2017) Argentina Clinical trial 55/ 92 6- 17 EAPD Gr I: Applications of fluoride varnish (3x 1 min), diet and OH counselling with 1000 ppm toothpaste Gr II: CPP-ACP(3x 1 min), diet and OH counselling with 1000 ppm toothpaste Gr III: 5% sodium fluoride varnish containing TCP (3x 1 min), diet and OH counselling with 1000 ppm toothpaste I: 5% sodium fluoride varnish (Duraphat)

II: CPP­ACP(Recaldent)

III: 5% sodium fluoride

varnish containing TCP (Clinpro)

1.5 LFvalues mild lesions: Gr I: T0: 18.57 ± 5.88 T1: 14.59 ± 4.88 Gr II: T0: 17.37 ± 7.22 T1: 15.15 ± 5.19 Gr III: T0: 20.04 ± 5.07 T1: 14.18 ± 3.65 (p<0.01) LFvalues moderate lesions: Gr I: T0: 56.88 ± 15.71 T1: 31 ± 11.97 Gr II: T0: 29.53 ± 17.85 T1: 27.31 ± 15.77 Gr III: T0: 28.85 ± 8.99 T1: 23.1 ± 7.74 (p<0.000005)

Clinpro was more effective in mild lesions Duraphat was more effective in moderate lesions

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3 Dixit et al. (2018) India Clinical trial 29/ 54 8- 14 EAPD, MIH severity (modifi ed Wetzel and Reckel scale) Gr I: Topical and

local infiltration and dental treatmentc

Gr II: Topical,

buccal infiltration and followed by

intraosseous local anesthetic technique and dental treatmentd

Topical anesthetic (Precaine), Local anesthetic (Septanest) Restoration or stainless steel crowns

Time for administration:

Gr I: 37.4±10.40 Gr II: 63.22±21.9 (p<0.004) Onset of LA: Gr I: 58.85±6.8 Gr II: 8.0±11.5 (p<0.0001) Required repeat: Gr I: 44.4% Gr II: 7.4% (p<0.004) Intraosseous technique required significantly more time for administration and showed significantly faster onset and lower required repeat of anesthetic administration than local infiltration.

4 Fragelli et al. (2017) Brazil Clinical trial 21/ 41

6- 8 EAPD Gr I (without MIH):

sealant applicatione Gr II (with MIH): sealant applicatione Fluoride varnish (Duraphat) Sealant (FluroShield) 18 According to USPHS- modified criteria: Gr I: 62,6% Gr II: 72% (p>0.05)

The failures in teeth with MIH were frequently associated with retention, secondary caries, marginal adaptation and discoloration, suggesting more difficult adhesion. 5 Fragelli et al. (2015) Brazil Prospective cohort study 21/ 48

6-9 EAPD GIC restorationf Glass Ionomer Cement

(Ketac Molar Easymix)

12 According to USPHS modifiedcriteria: 78% (p>0.05)

High integrity, mainly in single- surface tooth restorations. 6 Grossi et al. (2018) Brasil Clinical trial 44/ 60

7- 13 EAPD Glass hybrid restorationg

Glass hybrid restorative system (Equia Forte)

12 Success rate (resoration present or with slight defect around margin <0.5mm): 98.3%

Restoration using a glass hybrid restorative system performed in the field with ART technique proves to be an effective approach to preserve molars affected by MIH 7 Lygidakis et al. (2009) Greece Clinical trial 47/ 94 6- 7 EAPD Gr Ah: double adhesive, fissure sealant Gr Bh: fissure sealants without adhesive

Adhesive (One- step) Sealant (Fissurit) 48 Fully sealed: A:70.2%; B:25.5% Partially sealed: A:29.7%; B:44.6% Lost sealant: A: 0% B: 29.7% (p<0.001)

Sealants with prior application of a 5th generation system (2- step etch and rinse single- bottle adhesive) had greater retention

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8 Restrepo et al. (2016) Brazil Clinical trial 51/ 51 9-12 EAPD Gr I: Fluoride toothpaste (2x d.)+ 5% NaF varnish Gr II: Fluoride toothpaste (2x d.) 5% NaF varnish (Duraphat) Fluoride toothpaste (Colgate Total with 1.450 ppm fluoride) 1 QLF: Group I: T0: −7.47 ± 0.43 T1: −6.32 ± 0.50; Group II: T0: −7.22 ± 0.40; T1: −6.43 ± 0.64 (p>0.05) No significant changes in both mean levels of fluorescence and area over time 9 Souza et al. (2016) Brazil Clinical trial 18/ 41

6- 12 EAPD SEAi Group

TEAj Group

SEA (Clearfil SE Bond), TEA (Adper Scotchbond Multi-Purpose)

Composite resin (Filtek Z350 XT, 3M Espe) 18 According to USPHS- modified criteria: SEA: 68.4% TEA: 54.6% (p>0.304)

SEAs, as well as TEAs can be applied to restore molars affected by MIH, when a conservative cavity preparation is performed

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a: Single professional treatment: desensitizing paste containing 8% arginine and calcium carbonate (elmex Sensitive Professional desensitizing paste)

b: home-based program: brushing with desensitizing toothpaste containing 8% arginine, calcium carbonate with 1450 ppm fluoride with the toothbrush (elmex Sensitive Professional) provided (2x daily for at least 2 min) and use of the corresponding mouthwash (elmex Sensitive Professional) (20 ml for 30 s).

c: Group C: Topical anesthetic Precaine (Contains: Lidocaine 8%, Dibucaine 0.8%) and local infiltration local anesthetic technique with 27- gauge short needle by injecting 1.5 ml of 4% Articaine with 1:100,000 epinephrine (Septanest).

d: Group IO: Topical anesthetic Precaine (Contains: Lidocaine 8%, Dibucaine 0.8%) and buccal infiltration with local anesthetic technique with 27- gauge short needle (0.5 ml of 4% articaine with 1:100,000 epinephrine (Septanest), followed by intraosseous local anesthetic technique (0.7 ml of 4% articaine with 1:100,000 epinephrine with X-tip IO system (X-tip Intraosseous Anesthetic Delivery System, (Dentsply).

e: pretreatment with fluoride varnish (Duraphat)

f: Pretreatment by weekly application of 5% Fluoride varnish (Duraphat), for 1 month, oral hygiene instructions and removal of caries lesion or non- satisfactory atypical restorations

g: Caries removal according to ART(atraumatic restorative treatment), cavity conditioner (GC) (10 sec), glass hybrid restoration, resinous, light- cured surface sealant (Equia Coat)

h: Pretreatment: cleaning of fissures with round bur, bristle brush, non- fluoridated paste, 37% orthophosphoric acid

i: SEA= Self- etching adhesive, primer, adhesive application, composite resin restoration.

Pretreatment: Weekly fluoride varnish (1 mo) (Duraphat), temporary GIC restoration (2 mo) (Ketac Molar Easymix), plaque removal, infiltrative anesthesia, rubber dam, partial removal of GIC. j: TEA= Total- etch adhesive, Application 37,5% phosphoric acid, primer, adhesive, composite resin restoration. Pretreatment: Weekly fluoride varnish (1 mo) (Duraphat), temporary GIC restoration (2 mo) (Ketac Molar Easymix), plaque removal, infiltrative anesthesia, rubber dam, partial removal of GIC.

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5. REFERENCES

1 Willmott NS, Bryan RAE, Duggal MS. Molar-Incisor-Hypomineralisation: A literature review. Eur Arch of Paediatr Dent. 2008;9(4):172-179

2 Salanitri S, Seow WK. Developmental enamel defects in the primary dentition aetiology and clinical management. Aust Dent J. 2013;58:133-40

3 Martinez Gomez TP, Guinot Jimeno F, Bellet Dalmau LJ, Giner Tarrida L. Prevalence of molar-incisor hypomineralisation observed using transillumination in a group of children from Barcelona (Spain). Int J Paediatr Dent. 2012;22:100-9

4 Jalevik B. Prevalence and Diagnosis of Molar-Incisor-Hypomineralisation (MIH): a systematic review. Eur Arch Paediatr Dent. 2010;11(2):59-64.

5 Lydiakis NA, Wong F, Jälevik B, Vierrou AM, Alaluusua S, Espelid I. Best Clinical Practice Guidance for clinicians dealing with children presenting with Molar-Incisor-Hypomineralisation (MIH). An EAPD Policy Document. Eur Arch of Paediatr Dent. 2010;11(2):75-81

6 Da Costa- Silva CM, Ambrosano GM, Jeremias F, De Souza JF, Mialhe FL. Increase in severity of molar- incisor hypomineralization and its relationship with the colour of enamel opacity: a prospective cohort study. Int J of Paediatr Dent. 2011;21:333-341

7 Weerheijm KL, Duggal M, Mejàre I, Papagiannoulis L, Koch G, Martens LC, Hallonsten AL. Judgement criteria for Molar Incisor Hypomineralisation (MIH) in epidemiologic studies: a summary of the European meeting on MIH held in Athens. Eur J of Paediatr Dent 2003;3:110-113 8 Kellerhoff NM, Lussi A. Molar- incisor hypominerlization. Schweiz Monatsschr Zahnmed. 2004;114(3):243-53

9 Pansky B. Review of Medical Embryology, Ohio: MacMillan; 1982 [chapter 6]

10 AlQahtani SJ, Hector MP, Liversidge HM. Brief communication: the London atlas of human tooth development and eruption. American J of Physical Anthr. 2010;142(3):481-90

11 Silva MJ, Scurrah KJ, Craig JM, Manton DJ, Kilpatrick N. Etiology of molar incisor hypomineralisation- A systematic review. Community Dent Oral Epidemiol. 2016;44:342-353 12 Jedeon K, De la Dure-Molla M, Brookes SJ, Loiodice S, Marciano C, Kirkham J, Canivenc-Lavier M, Boudalia S, Bergès R, Harada H, Berdal A, Babajko S. Enamel Defects Reflect Exposure to Bisphenol A. Am J Pathol. 2013;183(1):108-118

13 Jalevik B, Klingerg GA. Dental treatment, dental fear and behaviour management problems in children with severe enamel hypomineralization of their permanent first molars. Int J Paed Dent. 2002;12:24-32

14 Mast P, Rodrigueztapia MT, Daeniker L, Krejci I. Understanding MIH: definition, differential diagnosis and treatment guidelines. Eur J Paediatr Dent. 2013;14(3):204-8

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15 Farah RA, Monk BC, Swain MV, Drummond BK, Protein content of molar- incisor hypomineralisation enamel, J. Dent. 2010;38: 591–596.

16 Farah RA, Swain MV, Drummond BK, Cook R, Atieh M, Mineral density of hypomineralised enamel. J. Dent. 2010;38: 50–58.

17 Fagrell TG, Dietz W, Jalevik B, Noren JG, Chemical, mechanical and morphological properties of hypomineralized enamel of permanent first molars. Acta Odontol. Scand. 2010;68: 215–222. 18 Fearne J, Anderson P, Davis GR. 3D X-ray microscopic study of the extent of variations in enamel density in first permanent molars with idiopathic enamel hypomineralisation. Br. J. Dent. 2004; 196:634–638

19 Cobourne M, Williams A, Harrison M. A guideline for the extraction of first permanent molars in children. 2014. Available at www.rcseng.ac.uk/-/media/files/ rcs/fds/publications/a-guideline-for-the-extraction-of- first-permanent-molars-in-children-rev-sept-2014.pdf (accessed March 2019). 20 Dixit UB, Joshi AV. Efficacy of Intraosseous Local Anesthesia for Restorative Procedures in Molar Incisor Hypomineralization- Affected teeth in Children. Contemp Clin Dent 2018;9:272-7 21 Sanchez-Figueras A (2006). Laser Fluorescence Detection of Dental Caries. Retrieved April 2019 from

http://www.kavousa.com/img_cpm/global/files/009/diagnodent/DIAGNOdent_LaserDetection.pdf 22 Raposo F, de Carvalho Rodrigues AC, Lia ÉN, Leal SC. Prevalence of Hypersensitivity in Teeth Affected by Molar-Incisor Hypomineralization (MIH). Caries Res. 2019;24:1-7

23 Bekes K, Heinzelmann K, Lettner S, Schaller HG. Efficacy of desensitizing products containing 8% arginine and calcium carbonate for hypersensitivity relief in MIH- affected molars: an 8-week clinical study. Clin Oral Invest. 2017; 21(7):2311-2317

24 Restrepo M, Jeremias F, Santos- Pinto L, Cordeiro RCL, Zuanon ACC. Effect of Fluoride Varnish on Enamel Remineralization in Anterior Teeth with Molar Incisor Hypomineralization. J Clin Pediatr Dent. 2016;40(3):207-10

25 Biondi AM, Cortese SG, Babino L, Fridman DE. Comparison of Mineral Density in Molar Incisor Hypomineralizationapplying fluoride varnishes and casein and casein phosphopeptide-amorphous calcium phosphate. Acta Odontol Latinoam. 2017; 30(3):118-23

26 Fragelli CMB, de Souza JF, Bussaneli DG, Jeremias F, Santos- Pinto L, Cordeiro RCL. Survival of sealants in molars affected by molar- incisor hypomineralization:18-month follow-up. Braz. Oral Res. 2017;31e30

27 Lygidakis NA, Dimou G, Stamataki E. Retention of fissure sealants using two different methods of application in teeth with hypomineralised molars (MIH). A 4 year clinical study. Eur Arch Paediatr Dent. 2009;10(4):223-6

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28 Fragelli CMB, de Souza JF, Bussaneli DG, Jeremias F, Santos- Pinto L, Cordeiro RCL. Molar incisor hypomineralization (MIH): conservative treatment management to restore affected

teeth. Braz Oral Res. 2015;29(1):1-7

29 Grossi JA, Cabral RN, Ribeiro APD, Leal SC. Glass hybrid Restorations as an alternative for restoring hypomineralized molars in the ART model. BMC Oral Health. 2018;18(1):65

30 De Souza JF, Fragelli CB, Jeremias F, Paschoal MAB, Santos-Pinto L, Cordeiro RCL. Eighteen- month clinical performance of composite resin restorations with two different adhesive systems for molars affected by molar incisor hypomineralization. Clin Oral Invest. 2017;21(5):1725-33

31 A Review of the Developmental Defects of Enamel Index (DDE Index): Commission on Oral Health, Research & Epidemiology. Report of an FDI Working Group. Int Dent J. 1992;42:411–26. 32 Steffen R, Krämer N, Bekes K. The Würzburg MIH concept: the MIH treatment need index (MIH TNI). Eur Arch Paediatr Dent. 2017;18:355-61

33 Cho SY, Ki Y, Chu V. Molar incisor hypomineralization in Hong Kong Chinese children. Int J Paediatr Dent. 2008;18:348-52.

34 Dantas-Neta NB, Moura LF, Cruz PF, Moura MS, Paiva SM, Martins CC, Lima MD. Impact of molar-incisor hypomineralization on oral health-related quality of life in schoolchildren. Braz Oral Res. 2016;30e117

35 Leal SC, Oliveira TRM., Ribeiro APD. Do parents and children perceive molar-incisor hypomineralization as an oral health problem? Int J Paediatr Dent. 2017;27:372–

36 Elhennawy K, Jost-Brinkmann PG, Manton DJ, Paris S, Schwendicke F. A cost- effectiveness analysis within German healthcare. J of Dent. 2017;63:65-71

37 Jälevik B, Klingberg G, Barregård L, Norén JG. The prevalence of demarcated opacities in permanent first molars in a group of Swedish children. Eur J Oral Sci. 2001;109:230-4

38 Brook AH, Elcock C, Hallonsten A-L, Poulsen S, Andreasen J, Koch G, Yeung CA, Dosanjh T. The development of a new index to measure enamel defects. in AH Brook (ed.), Dental

Morphology. Sheffield Academic Press, Sheffield, United Kingdom, 2001 pp. 59-66.

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ANNEX 1 Protocol of systematic review

Aim To analyze the publications related to Molar Incisor Hypomineralisation (MIH) with focus on treatment peculiarities

Tasks 1.search and select the publications for analysis

according to the inclusion and exclusion criteria. 2. to analyze and compare the results of the selected studies

3. To assess which treatment peculiarities are present in the treatment of Molar Incisor Hypomineralisation

METHODS

Eligibility criteria PICOS

P- Participants: children till the age of 18 with ≥ 1 hypomineralized permanent molar or incisor I- Intervention:

- visual/ tactile examination - optic- transillumination - sensitivity

- pain

C- Comparison: with treatment of teeth without MIH

O- Outcome: differences in treatment of MIH and non- MIH teeth (diagnosis, anaesthesia, materials, follow- up period)

S- Study design selection: clinical study, clinical trial

Inclusion criteria:

1. Publications written in English

2. Report characteristics not older than 10 years

3. Studies performed in vivo and on humans 4. Full texts

Exclusion criteria:

1. Non- full articles or inaccessible unless purchased

2. Studies including adults 3. Studies in vitro, on animals 4. Non- English articles

5. Articles published more than 10 years ago Information sources Electronic databases: PUBMED, Cochrane library,

Embase, MEDLINE

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ANNEX 2 EVALUATION FORM OF THE MASTER’S THESIS

FOR THE MEMBER OF DEFENCE COMMITTEE Graduate student ___________________________________,

of the year ______, and the group _____ of the integrated study programme of Odontology Master’s Thesis title:

………...……….………...…………...……... ………...….………...……...

No. MT evaluation aspects Evaluation

Yes Partially No 1 Has the student’s presentation lasted for more than 10 minutes?

2 Has the student presented the main problem of the Master’s thesis, its aim and tasks? 3 Has the student provided information on research methodology and main research instruments? 4 Has the student presented the received results comprehensively? 5 Have the visual aids been informative and easy to understand? 6 Has the logical sequence of report been observed?

7 Have the conclusions been presented? Are they resulting from the results?

8 Have the practical recommendations been presented?

9 Have the questions of the reviewer and commission’s members been answered correctly and thoroughly? 10 Is the Master’s thesis in compliance with the essence of the selected study programme? Remarks of the member of evaluation committee of Master’s Thesis

______________________________________________________________________________ ______________________________________________________________________________ ______________________________________________________________________________ ______________________________________________________________________________ Evaluation of the Master’s Thesis

_____________________________________________________________________________ Member of the MT evaluation committee:

________________ ___________________________ _____________________

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