MIH Best Practice

European Archives of Paediatric Dentistry
https://doi.org/10.1007/s40368-021-00668-5
INVITED REVIEW
Best clinical practice guidance for clinicians dealing with children

presenting with molar‑incisor‑hypomineralisation (MIH): an updated
European Academy of Paediatric Dentistry policy document
N. A. Lygidakis1 · E. Garot2,3,4 · C. Somani5 · G. D. Taylor6 · P. Rouas2,3,4 · F. S. L. Wong5
Received: 12 September 2021 / Accepted: 22 September 2021

© The Author(s) 2021
Abstract
Aim To update the existing European Academy of Paediatric Dentistry (EAPD) 2010 policy document on the ‘Best Clinical
Practice guidance for clinicians dealing with children presenting with Molar-Incisor-Hypomineralisation (MIH).’
Methods Experts, assigned the EAPD, worked on two different topics: (A) Aetiological factors involved in MIH, and (B)
Treatment options for the clinical management of MIH. The group prepared two detailed systematic reviews of the existing
literature relevant to the topics and following a consensus process produced the updated EAPD policy document on the ‘Best
Clinical Practice guidance for clinicians dealing with children presenting with molar-incisor-hypomineralisation (MIH).’ The
GRADE system was used to assess the quality of evidence regarding aetiology and treatment which was judged as HIGH,
MODERATE, LOW or VERY LOW, while the GRADE criteria were used to indicate the strength of recommendation
regarding treatment options as STRONG or WEAK/CONDITIONAL.
Results (A) Regarding aetiology, it is confirmed that MIH has a multifactorial aetiology with the duration, strength and
timing of occurrence of the aetiological factors being responsible for the variable clinical characteristics of the defect. Peri-
natal hypoxia, prematurity and other hypoxia related perinatal problems, including caesarean section, appear to increase the
risk of having MIH, while certain infant and childhood illnesses are also linked with MIH. In addition, genetic predisposi-
tion and the role of epigenetic influences are becoming clearer following twin studies and genome and single-nucleotide
polymorphisms analyses in patients and families. Missing genetic information might be the final key to truly understand
MIH aetiology. (B) Regarding treatment options, composite restorations, preformed metal crowns and laboratory indirect
restorations provide high success rates for the posterior teeth in appropriate cases, while scheduled extractions provide an
established alternative option in severe cases. There is great need for further clinical and laboratory studies evaluating new
materials and non-invasive/micro-invasive techniques for anterior teeth, especially when aesthetic and oral health related
quality of life (OHRQoL) issues are concerned.
Conclusions MIH has been studied more extensively in the last decade. Its aetiology follows the multifactorial model, involv-
ing systemic medical and genetic factors. Further focused laboratory research and prospective clinical studies are needed
to elucidate any additional factors and refine the model. Successful preventive and treatment options have been studied and
established. The appropriate choice depends on the severity of the defects and the age of the patient. EAPD encourages the
use of all available treatment options, whilst in severe cases, scheduled extractions should be considered.
Keywords Molar incisor hypomineralisation · MIH · Clinical practice · Treatment · Aetiology · Policy document · EAPD ·
Guidelines
Background
The European Academy of Paediatric Dentistry (EAPD) was

the first international scientific organisation that extensively
* N. A. Lygidakis studied molar-incisor- hypomineralisation (MIH) and devel-
lygidakis@ath.forthnet.gr oped a policy document and relevant publications. The first
Extended author information available on the last page of the article policy document was published in 2010 being produced after
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Vol.:(0123456789)
an Interim Seminar and Workshop organised by the EAPD at the 12th EAPD Interim Seminar in Oslo. The document
in Helsinki in May 2009 (Lygidakis et al. 2010). At that was assessed by the Clinical Affairs Committee of EAPD
time, a comprehensive search of the literature was under- for further comments and finally published in the European
taken and presented by the invited speakers. This revealed Archives of Paediatric Dentistry.
a limited number of high-quality research studies on the
topic. Due to the small number, and their shortcomings, it
was evident that a ‘Guidelines Diagram’ according to the
SIGN Methodology, popular at the time, was impossible to Methods
be made. However, it was agreed by all of the workshop
speakers and experts that there was a great need for a guide Instead of the SIGN methodology, that was used in 2009,
to support clinicians encountering children with MIH. This the present updated ‘MIH best clinical practice guidance’
led to the ‘Best Clinical Practice Guidance’ being devel- employed the GRADE system (Guyatt et al. 2008; Ryan
oped and was based on a combination of available current and Hill 2016) to assess the quality of existing evidence for
evidence and consensus expert opinion from those attending both the aetiology and the treatment options applied in MIH.
the workshop. The document became extremely popular and The quality of evidence was judged as HIGH, MODERATE,
is still used internationally by clinicians dealing with MIH. LOW or VERY LOW, based on assessment of eight criteria
Ten years later, in 2019, the EAPD assigned two of the which may have an impact to the confidence in the results.
previous experts to lead a study group to update the existing These criteria are risk of bias, indirectness, inconsistency,
‘Best Clinical Practice Guidance’. The study group, com- imprecision, publication bias, large magnitude of effect, dose
prising six experts, worked intensively for eight months response and the effect of all plausible confounding factors
prior to the 12th EAPD Interim Seminar in Oslo, on two for reducing the effect or suggest a spurious effect. Follow-
different topics: (A) aetiological factors involved in MIH, ing the quality assessment, the same approach was used to
and (B) treatment options for the clinical management of indicate the strength of recommendation for each treatment
MIH. The group prepared two detailed systematic reviews option available, as STRONG or WEAK/CONDITIONAL.
and meta-analyses, where appropriate, of the existing litera- The interpretation of the gradings for quality of evidence and
ture relevant to the topics (Garot et al. 2021; Somani et al. strength of recommendation are shown in Tables 1 and 2.
2021). Thereafter, and following a consensus process, the Details of all studies evaluated and the methodology imple-
updated EAPD policy document on the ‘Best Clinical Prac- mented, are included in the two relevant systematic reviews
tice guidance for clinicians treating children with molar inci- prepared by the study group (Garot et al. 2021; Somani et al.
sor hypomineralisation (MIH)’ was produced and presented 2021).
Table 1 GRADE ratings and their interpretation

Grades of evidence Interpretation
quality
High We are very confident that the true effect lies close to that of the estimate of the effect
Moderate We are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there
is a possibility that it is substantially different
Low Our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect
Very low We have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate
of effect
Table from the GRADE Handbook, available at: http://gdt.guidelinedevelopment.org/app/handbook/handbook.html#h.9rdbelsnu4iy
Table 2 Strengths of recommendation for patients and clinicians

Strong recommendation Weak/Conditional recommendation
For patients Most people would want the recommended course of action Most people would want the recommended course of action, but
and only a small proportion would not many would not
For clinicians Most patients should receive the recommended course of Different choices will be appropriate for different patients and
action each patient should be advised for a management decision
consistent with her/his values and preferences
Adapted from: Guyatt et al. GRADE Working Group. Rating quality of evidence and strength of recommendations: going from evidence to rec-
ommendations. BMJ.2008; 336:1049–51
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Terminology and diagnosis of MIH Diagnostic criteria
Terminology EAPD reinforces the use of the specific clinical signs and
symptoms for the diagnosis of MIH, as previously described
Regarding terminology, EAPD at present reinforces the in the earlier EAPD publications (Weerheijm et al. 2003;
use of the term MIH, as it has been established previously Lygidakis et al. 2010). The use of intraoral X-Rays may add
by the EAPD criteria (Weerheijm et al. 2003; Lygidakis to the diagnosis (Aps et al. 2020). These criteria are shown
et al. 2010) and it is well known and adopted globally. in Table 3.
However, as it was proposed in the previous policy docu-
ment, there is a risk that the current definition of MIH Severity of the defects
could be misleading and may result in an under-estima-
tion of the defect. Demarcated opacities, similar to MIH, EAPD reinforces the baseline classification of the defects as
have been observed in the tips of permanent canine cusps, mild or severe (Table 4), as they have been detailed previ-
second permanent molars and the premolars. Future work- ously, to clarify the diagnosis and formulate an appropriate
shops should focus their efforts to formulate a more inclu- treatment plan (Lygidakis et al. 2010).
sive term. In addition, the term HSPM (hypo-mineralised
second primary molars) has now been clearly established Recording MIH for epidemiological studies
indicating demarcated opacities of the same type as MIH
on second primary molars (Elfrink et al. 2012). Despite Regarding epidemiological studies, the approach presented
the limitations of the few published studies, it has been by Ghanim et al. (2015) seems to be the most appropriate
clearly shown that the presence of HSPM is predictive for at present, as it combines the well-established elements of
MIH, with higher MIH prevalence in the presence of mild the EAPD criteria and the modified index of developmental
HSPM (Garot et al. 2018). defects of enamel (mDDE) (Clarkson and O’Mullane 1989).
Table 3 EAPD Diagnostic criteria of MIH (adopted from Weerheijm et al. 2003; Lygidakis et al. 2010)
Diagnostic feature Description of the defect
Teeth involved One to all four permanent first molars (FPM) with enamel hypomineralisation
Simultaneously, the permanent incisors can be affected
At least one FPM has to be affected for a diagnosis of MIH
The more affected the molars, the more incisors involved and the more severe the defects
The defects may also be seen at the second primary molars, premolars, second permanent molars and the tip
of the canines
Demarcated opacities Clearly demarcated opacities presenting with an alteration in the translucency of the enamel
Variability in colour, size and shape
White, creamy or yellow to brownish colour
Only defects greater than 1 mm should be considered
Post-eruptive enamel breakdown Severely affected enamel breaks down following tooth eruption, due to masticatory forces
Loss of the initially formed surface and variable degree of porosity of the remaining hypomineralised areas
The loss is often associated with a pre-existing demarcated opacity
Areas of exposed dentine and subsequent caries development
Sensitivity Affected teeth frequently reveal sensitivity, ranging from mild response to external stimuli to spontaneous
hypersensitivity
MIH molars may be difficult to anesthetize
Atypical restorations The size and shape of restorations are not conforming to the typical caries picture
In molars the restorations are extended to the buccal or palatal/lingual smooth surface
An opacity can be frequently noticed at the margins of the restorations
First permanent molars and incisors with restorations having similar extensions as MIH opacities are recom-
mended to be judged as that
Extraction of molars Extracted teeth can be defined as having MIH when there are:
due to MIH - Relevant notes in the records
- Demarcated opacities or atypical restorations on the other first molars
- Typical demarcated opacities in the incisors
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This approach grades the clinical status of MIH and its and a long form for more detailed community-based or
extent on the involved tooth surface as well as other enamel clinic-based studies that use both EAPD and mDDE criteria
defects and additionally includes any existence of HSPM (Ghanim et al. 2015, 2017). The short data form is designed
in the same child (Ghanim et al. 2015). The basic features to grade only index teeth which have been mentioned in
are shown in Figs. 1 and 2. To take into account the varied the definition of MIH and HSPM, namely first permanent
needs and objectives of epidemiological studies, two forms molars, permanent incisors, and second primary molars. The
of the examination chart have been proposed, a short form long data form is formulated to diagnose all teeth at surface
for simple screening surveys using only the EAPD criteria
Table 4 Description of severity Severity level Signs and symptoms

level according to the EAPD
criteria (adopted from Jälevik Mild Demarcated enamel opacities without enamel breakdown
2010; Lygidakis et al. 2010) Induced sensitivity to external stimuli e.g., air/water but not brushing
Mild aesthetic concerns on discolouration of the incisors
Severe Demarcated enamel opacities with breakdown and caries
Spontaneous and persistent hypersensitivity affecting function e.g.,
brushing, mastication
Strong aesthetic concerns that may have socio-psychological impact
0 = No visible enamel defect.

1 = Enamel defect, not MIH/HSPM.
2 = White, creamy, yellow or brown
demarcated opacies.
3 = PEB.
4 = Atypical restoraon.
5 = Atypical caries.
6 = Missing due to MIH/HSPM.
7 = Cannot be scored.
Fig. 1 MIH/HSPM clinical data short recording sheet and scoring details. Only teeth involved in MIH/HSPM and the relevant MIH characteris-
tics are included (Ghanim et al. 2015)
0 = No visible enamel defect.

1 = Enamel defect, non-MIH/HSPM
11 = Diffuse opacies
12= Hypoplasia
13 = Amelogenesis imperfecta
14= Hypomineralisaon defect
(not MIH/HSPM)
2 = Demarcated opacies
21 = White or creamy
demarcated opacies
22 = Yellow or brown
demarcated opacies
3 = Post-erupve enamel
breakdown (PEB)
Lesion extension criteria (Index teeth only, for scores 2 to 6) 4 = Atypical restoraon
I = less than one third of the tooth surface affected. 5 = Atypical caries
II = at least one third but less than two thirds of the surface affected. 6 = Missing due to MIH/HSPM
7 = Cannot be scored
III = at least two thirds of the tooth surface affected.
Fig. 2 MIH/HSPM clinical data long recording sheet and scoring details. Teeth involved in MIH/HSPM are highlighted grey. MIH and mDDE
characteristics in all existing teeth are included (Ghanim et al. 2015)
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level available at the time of the dental examination in addi- countries, mainly in regions with limited access to dental
tion to MIH/HSPM-specific index teeth. care, shoulder the majority of new cases of MIH.
Recently, one further index has been developed that is To show the global MIH prevalence at present, the
useful for determining mainly the treatment needs of chil- weighted mean for each country/region was calculated
dren with MIH (Steffen et al. 2017). The index is defined using existing data and is shown using a colour gradient
as MIH Treatment Need Index (MIH-TNI) and has been on a world map (Fig. 3). In the most recent prevalence sys-
designed for identifying patients with MIH, providing infor- tematic review (Schwendicke et al. 2018), only the studies
mation about the severity, and describing their subsequent from 2000 to May 2017 were included. In preparation of
treatment needs. this policy document, it was noted that more prevalence
studies have been published between May 2017 and Sep-
tember 2020. It was agreed by all authors of this policy
Prevalence data of MIH document to include these additional prevalence figures in
our world prevalence map.
The first epidemiological data, from national studies car- Evaluating all existing prevalence data, it appears that
ried out in European countries, reported prevalence varying MIH is still not confidently diagnosed by general prac-
from 3.6 to 25% (Weerheijm and Mejàre 2003). Subsequent titioners, in contrast to paediatric dentists who are more
reviews of the literature showed an even wider range in the familiar with the condition. Patients sometimes present
worldwide MIH prevalence (2.9–44%) (Jälevik 2010; Elfrink with severe destruction in their first permanent molars,
et al. 2015). Comparing the results of different studies in atypical restorations, or even with extracted molars. Such
the past was difficult because of the use of different indices, cases, together with the absence of opacities, could be
diagnostic criteria, registration methods and age groups. misdiagnosed as caries. Therefore, the prevalence of MIH
In the last decade, the number of studies evaluating the could be underestimated, unless clinicians with more
prevalence of MIH at national or regional level has signifi- experience and training in observing MIH diagnosis are
cantly increased. In addition, most studies are now routinely involved in national epidemiological studies (Zhao et al.
using the standardised EAPD diagnostic and epidemio- 2018).
logical criteria for MIH (Elfrink et al. 2015; Ghanim et al. It is worth noting that the current mean prevalence fig-
2017). Two recent systematic reviews and meta-analyses ures of MIH are very close to that highlighted in the first
revealed similar global mean prevalence; the first one 14.2% reported prevalence study in 1987, although the estab-
(8.1–21.1%) (Zhao et al. 2018; Dave and Taylor 2018) and lished MIH EAPD diagnostic criteria did not exist at that
the second 12.9% (11.7–14.3%) (Schwendicke et al. 2018). time; their findings estimated a prevalence 13–16% fol-
Both reviews established significant prevalence differences lowing examination of 2226 patients born between 1966
between super-regions, regions and countries, while certain and 1974 in Sweden (Koch et al. 1987). This comparison,
Fig. 3 World map of MIH

prevalence at present
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added to the absence of any relevant scientific evidence, authors established a link between the rs5979395 SNP of
indicates that over time the prevalence of MIH may not the AMELX gene (Xq22) and MIH (OR 11.7; P = 0.006)
have increased, despite opposing suggestions. with 97% of these participants with MIH carrying the
rs5979395*G allele (Jeremias et al. 2016). Other authors
have identified the rs13058467 locus, located near the
Aetiology of MIH SCUBE1 gene on chromosome 22 (p<3.72E7), as a pos-
sible locus related to MIH (Kühnisch et al. 2014). The
General considerations SCUBE1 gene plays a role in the development of the crani-
ofacial region, and in a mouse model, it was found to be
In the 2010 ‘policy document’, it was stated that ‘It is localised to the dental papilla of both incisor and molar
likely that MIH is not caused by one specific factor. teeth (Xavier et al. 2009). A genetic predisposition to MIH
Several harmful agents/conditions may act together and in conjunction with one or several other aetiological fac-
increase the risk of MIH occurring additively or even syn- tors has been proposed, as some authors identified certain
ergistically.’ (Lygidakis et al. 2010). Since 2010, data from variants in amelogenesis-related genes ENAM, AMELX
more aetiological studies support and confirm this state- or MMP20 (Jeremias et al. 2013a, b, 2016; Kühnisch et al.
ment (Table 5). The evidence now re-affirms that in MIH, 2014; Hočevar et al. 2020; Pang et al. 2020) or immune
certain systemic and genetic factors act synergistically to response-related genes (Bussaneli et al. 2019) in children
produce enamel hypomineralisation. In addition, the dura- with MIH. More recently, epigenetic influences of certain
tion, strength and timing of these factors may be respon- environmental factors have also been established (Teix-
sible for the varied clinical characteristics of the defect. eira et al. 2018; Vieira 2019; Vieira and Manton 2019).
More than 30 systemic aetiological hypotheses have Epigenetics describes the way in which gene–environ-
been identified over the last 10 years; some are well ment and gene–gene interactions cause the expression of
established, others are more contemporary. The different a phenotype. In other words, it is possible that epigenetics
aetiological hypotheses can be linked to the pre-, peri- regulates the different systemic factors that influence the
and post-natal periods, as alterations in the function of function of the enamel proteins involved in MIH (Küh-
the ameloblasts during the maturation phase may occur nisch et al. 2014). In a recent study, it has been reported
between the end of pregnancy and the age of 4 years (Ala- that individual variations in different genes have an addi-
luusua 2010). tive effect on the development of MIH, which most likely
occurs under the influence of specific environmental/sys-
temic factors (Hočevar et al. 2020).
Genetics/Epigenetics All the above suggest that MIH follows a multifactorial
model with genetic and/or epigenetic components becoming
There has been an increase in research focusing on the more prominent in the more recently established evidence
genetics associated with the aetiology of MIH. The levels (Pang et al. 2020; Bussaneli et al. 2021).
of MIH-affected teeth observed between monozygotic and
dizygotic twins in clinical studies (Teixeira et al. 2018), Systemic and medical aetiological factors
infer the relative importance of genetics. It is worth not-
ing, however, that such studies have certain methodology a. Prenatal period
limitations and twins are more likely to encounter similar
proposed aetiological factors in the peri- and post-natal In a recent systematic review, no specific illness during
periods when compared to non-twin births (Lygidakis the last trimester of pregnancy was associated with MIH
et al. 2010). (Garot et al. 2021). Additionally, there is no convincing evi-
Recent studies evaluated single-nucleotide polymor- dence of an association between drugs taken during preg-
phisms (SNP) in a group of individuals with and without nancy, maternal smoking or maternal alcohol intake and
MIH (Jeremias et al. 2013a, b, 2016). The SNP corre- MIH (Fatturi et al. 2019; Garot et al. 2021). It has been
sponds to the variation (polymorphism) of a single base reported that certain medical problems are more frequently
pair in the genome, and could be the basis of our species' present in mothers of children with MIH (Whatling and
susceptibility to certain diseases. The genetic associations Fearne 2008; Sönmez et al. 2013; Koruyucu et al. 2018;
between SNP rs3790506 (TUFT1) and SNP rs946252 Fatturi et al. 2019; Mejia et al. 2019). However, what con-
(AMELX) and MIH were investigated but no association stituted as maternal illnesses differed substantially among
between these SNPs and MIH was demonstrated (Jere- the studies and most were determined retrospectively from
mias et al. 2013a, b). However, in a later study, the same interviewing the mother, thus introducing a recall bias.
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Table 5 GRADE quality of evidence of included studies related to aetiology

Aetiological factor (in alphabetical order) No of studies No of participants No of participants with Quality of evidence
the factor
Allergies 6 2432 518 Low

Antibiotics 19 11,703a 2330 Low
Asthma 14 8104a 1227 Low
Asthma drug 5 3669 981 Low
Breast feeding > 12 months 8 8189 972 Low
Breast feeding > 6 months 7 4810 928 Low
Bronchitis 12 9473a 1270 Low
Caesarean 17 10,886a 2336 Low
Celiac disease 1 80 40 Very low
Chicken pox 14 9845 1437 Very low
Diarrhoea 7 6893 908 Low
Eclampsia 4 5409 592 Low
Epigenetic (monozygotic twins) 1 334 188 High
Fever 20 14,128a 2408 Low
Fluoride 1 3233 2507 Low
Gastric disorders 8 6266 647 Low
Genetic (SNP association) 4 1456 ND High
Gestational diabetes 4 1554 406 Very low
Gestational hypertension 9 7611 1009 Low
Hypoxia at birth 16 9867a 1859 Low
Incubator 5 5628 702 Moderate
Jaundice 4 1220 220 Very low
Kidney diseases 7 3758 754 Low
Low birth weight 11 10,150a 1779 Low
Malnutrition 4 1464 342 Very low
Maternal diseases 14 15,312a 1853 Low
Maternal fever 4 4921 536 Low
Maternal smoking 6 4227 1278 Low
Maternal Urinary disease 4 5410 592 Low
Measles 3 4139 348 Low
Medication during pregnancy 8 3879 722 Moderate
Otitis 17 9421a 1417 Low
Pneumonia 12 10,021a 1581 Low
Pre-eclampsia 7 7517 1042 Low
Prematurity 19 12,307a 2405 Low
Rhinitis 5 3281 600 Low
Rubeola 2 5338 516 Low
Sinusitis 3 1401 311 Low
Throat infections 3 2403 405 Low
Tonsillitis 4 1290 261 Very low
Urinary tract infection 11 8675a 1015 Low
Vitamin D deficiency 1 1840 ND High
a
Studies with large number of examined children where (regardless the low quality of evidence resulting from the retrospective methodology)
the meta-analysis revealed odds ratios indicating increased risk of having MIH (Garot et al. 2021).
13
b. Perinatal period diseases, pneumonia and asthma, were also found to be

associated with MIH (Garot et al. 2021). It is known that
In the perinatal period, different parameters, such as antibiotics are prescribed to manage many of these condi-
hypoxia, premature birth, low birth weight, birth complica- tions. Therefore, it is likely that the presence of a particular
tions and caesarean section, presenting alone or in combi- disease, rather than the antibiotics prescribed to manage it,
nation, appear to be associated with the presence of MIH is associated with MIH. In addition, no association between
(Garot et al. 2021). This recent systematic review and meta- MIH and rubeola, sinusitis, jaundice, rhinitis, malnutrition,
analysis demonstrated that hypoxia at birth, reported in 16 throat infections, allergies and diarrhoea was found in the
studies (n = 9867 participants), substantially increased the most recent systematic review (Garot et al. 2021).
possibility of having MIH (OR 2.76 [2.09, 3.64]; P < 0.0001) Recording the history of childhood diseases across most
(Garot et al. 2021). Hypoxia may be associated with birth- studies frequently relied on the recall of the parents, intro-
related medical problems noted above, or in addition to pro- ducing a recall bias. Nevertheless, accepting this as a limi-
longed delivery (Ananth and Chauhan 2012; Esteves-Pereira tation of the current evidence, there appears to be a clear
et al. 2021). association between certain systemic factors and MIH in
When analysed in isolation, prematurity was signifi- the post-natal period.
cantly associated with MIH (OR 1.45; 95% CI 1.24–1.70;
P = 0.0002) (Garot et al. 2021). This finding is in contrast Comments arising from the evaluation
with that reported in a previous systematic review and of the existing aetiology literature
meta-analysis (Fatturi et al. 2019). A similar conclusion
was observed in relation to the positive effect of caesarean Is there a link between the duration, strength and timing
section (Garot et al. 2021), as it appeared not to be associ- of aetiological factors action and the development of MIH?
ated with MIH in the previous systematic review (Fatturi
et al. 2019). The most recent review included 17 studies In the previous ‘EAPD Policy Document’ of 2010, the fol-
(n = 10,886 participants) and indicated that caesarean section lowing comment was made by the working group; ‘Is the
increased the possibility of having MIH (OR 1.45; 95% CI aetiology of MIH likely to be a question of dosage or dura-
1.09–1.93; P = 0.01) (Garot et al. 2021). tion of the effect during a critical time in tooth develop-
These conflicting results could be explained by the num- ment?’ (Lygidakis et al. 2010).
ber of included studies in the two reviews. Garot et al. (2021) Recent evidence seems to support this statement. Given
included and evaluated almost twice as many studies to that the asymmetrical nature of the hypomineralised defect in
by Fatturi et al. (2019), and therefore provides a stronger terms of location and severity, the hypothesis that short
argument for known peri-natal systemic aetiological factors events result in less severe defects is supported by the studies
in the development of MIH (Table 5). of Sidaly et al. (2015, 2016). These studies have shown that
a short episode of induced severe hypoxia (less than 5 min)
c. Postnatal period in adult mice can cause a single confined area of enamel
hypomineralisation on their incisors, with the position and
During the post-natal period, many factors may intervene character of the defect being related to the functional stage
in the life of the child from birth to 4 years, the suggested at which the ameloblasts are affected (Sidaly et al. 2016). In
critical period for MIH development (Lygidakis et al. 2008b; contrast, large-scale case–control studies have shown that
Whatling and Fearne 2008). The hypothetical aetiological the number of the affected teeth was greater when more aeti-
factors include effects by environmental pollutants, child- ological factors were involved for longer periods (Lygidakis
hood diseases and medication. et al. 2008a). Similarly, in the prenatal period, repeated epi-
Previous studies have suggested that environmental sodes of maternal high fever during pregnancy result in chil-
pollutants found in breast milk might be associated with dren having 2.54 times greater chance of developing severe
MIH (Alaluusua et al. 1996). However, none of the stud- MIH (Dantas-Neta et al. 2016).
ies included in the most recent meta-analysis found a link In addition to systemic aetiological factors, genes and
between the duration of breastfeeding and the occurrence of epigenetic actions appear to also mediate environmental
MIH (Garot et al. 2021). This was a similar finding to that by influences on the gene expression. This might support the
Fatturi et al. (2019) who reported there was no link between view that MIH occurs as a result of certain life events, while
breast-feeding and MIH. the mechanism linking systemic and genetic factors might
With regard to the use of medication, only antibiotics explain the different severities of MIH in teeth forming at
have been linked to MIH (Fatturi et al. 2019; Garot et al. the same time although in different locations (Vieira 2019;
2021). Childhood illnesses, such as measles, urinary tract Vieira and Manton 2019).
infection, bronchitis, otitis, gastric disorders, fever, kidney
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Are archaeological findings helpful in studying The publication of more retrospective aetiological studies
the aetiology of MIH? would not add anything new to the existing evidence base.
The increasing number of MIH cases in archaeological GRADE rating for the quality of evidence
skeletal remains in France and England may help to lower of the aetiology studies in MIH
the significance of some reported aetiological factors, such
as Bisphenol A and other endocrine disruptors, antibiotics, The GRADE system was used to assess the quality of stud-
dioxins, and other pollutants, as these were not present in ies on the aetiology of MIH which was judged as HIGH,
the medieval time (Ogden et al. 2008; Curzon et al. 2015; MODERATE, LOW or VERY LOW (Table 5) based on the
Garot et al. 2017, 2019). Some of these studies, besides assessment of eight criteria which can influence the con-
clinical observations, undertook laboratory investigations fidence of the results (Guyatt et al. 2008). Details of the
to confirm the observational findings (Garot et al. 2017). implementation of all criteria regarding the included studies
There are, however, some opposing clinical observations are shown in the supplement as Appendix 1.
(Kühnisch 2017), reporting a low prevalence of MIH in
adults’ archaeological case series from Germany. Despite
this inconsistency, this line of thinking should be further Treatment approaches for MIH teeth
investigated, as it might easily help to exclude contemporary
living conditions from the aetiology of MIH. a. Treatment of posterior teeth
Appropriate treatment decisions for posterior teeth should

Are the current studies investigating systemic aetiological
take into consideration several factors (Table 6), arising from
factors robust enough to draw definitive results
increased clinical knowledge and relevant clinical and labo-
and answers regarding MIH aetiology?
ratory studies.
As previously stated, ‘The problem of most clinical studies
Preventive approach Early identification of MIH-affected
relating MIH or MIH like lesions with medical conditions/
teeth is key to the management of affected molars. As these
problems, so far, is that they are retrospective. The informa-
teeth are at higher risk of caries (Jeremias et al. 2013a, b;
tion has been obtained by questionnaires or an interview,
Bullio Fragelli et al. 2015), early prevention is very impor-
which rely on individual memory and can lead to inaccura-
tant. Due to the presence of hypersensitivity, children may
cies’ (Alaluusua 2010). Unfortunately, a similar situation
avoid oral hygiene procedures. Therefore, enhanced oral
exists currently, as most studies are retrospective, relying on
hygiene instruction and dietary advice should be provided
parent interviews to recall information (Garot et al. 2021).
and reinforced regularly to both children and their carers.
Such studies results are biased and, regardless of which sta-
Placement of topical fluoride varnish is also advised, pri-
tistical approach is undertaken, are usually compromised.
marily for preventing caries in permanent teeth (Marinho
Although the planning of prospective studies is indeed very
et al. 2013; Toumba et al. 2019). However a longitudinal
difficult for such a long period of follow-up (from preg-
study found that despite placement of fluoride varnish on
nancy up to until the age of 8 years), their future planning
MIH-affected molars, an increased risk of caries and post-
appears a necessity to further clarify the aetiology of MIH.
eruptive breakdown was still observed (Bullio Fragelli et al.
Table 6 Factors to be considered for appropriate treatment planning for posterior teeth
At patient level At oral level At tooth level
Age of patient Number of affected teeth Size of defect

Medical history DMFT Location of defect
Ability to cooperate Developmental stage Number of surfaces involved
Presence/absence of symptoms Occlusion Presence/absence of post-eruptive breakdown
Access to general dental care Presence/absence of crowding Presence/absence of atypical or typical cari-
ous lesions and extent
Access to specialist care (paediatric dental/ Presence of third permanent molars Pulpal involvement
orthodontic)
Hypodontia History of dental abscess/facial cellulitis
Need for future orthodontic treatment
13
2015). Combining topical fluoride varnish placement with been associated with an inhibition of crystal growth and
frequent recall intervals of 3–6 months and enhanced pre- overall reduction in the mineral quantity and quality of
ventive measures allow the practitioner to closely monitor MIH-affected enamel (Farah et al. 2010). As such, these
the affected teeth for breakdown. Silver diamine fluoride characteristics should be considered when deciding how to
has been used successfully in primary teeth to arrest caries restore these teeth.
(Seifo et al. 2019). However, there are currently no pub-
lished clinical studies documenting its use on MIH-affected Restoration with composite resin is a predictable option,
teeth. For fully erupted molars, resin-based fissure sealants with high success rates, if placed under rubber dam isolation
should be considered the first line approach in preventing to ensure good moisture control (Lygidakis et al. 2003; Kot-
both dental caries and post-eruptive breakdown (Lygidakis sanos et al. 2005; Mejare et al. 2005; Rolim et al. 2021). The
et al. 2009; Fragelli et al. 2017). The use of an adhesive dur- technique is simple, can be completed in one appointment
ing fissure sealant placement is advised as it has been clearly and defective restorations can be easily repaired. Regarding
shown to increase the retention rate (Lygidakis et al. 2009). the cavity design, total removal of hypomineralised enamel
is suggested for the restoration to be successful (Lygidakis
Atraumatic restorations Where a child lacks co-operation for et al. 2010), as adhesion to remaining MIH-affected enamel
invasive treatment requiring local anaesthetic, or is unable is poorer with a reduced bond strength (Lagarde et al. 2020).
to access routine dental care, a glass ionomer cement (GIC) Whilst there is a shift in caries management to minimally
restoration can be placed in the interim, until a suitable res- invasive approaches, poor success rates have been reported
toration can be placed, or before an age-scheduled extrac- in the few studies that have placed composite restorations
tion, to protect the tooth from post-eruptive breakdown and using a non-invasive approach for MIH-affected molars
hypersensitivity. As a hydrophilic material having the added (Sonmez and Saat 2017; Linner et al. 2020). Pre-treatment
benefit of fluoride release, GIC can be used where ideal with 5% sodium hypochlorite and the use of self-etch or
moisture control is not possible. The inferior mechanical total-etch techniques have been investigated clinically but the
properties of GIC, however, preclude their use in stress-bear- results thus far show that none of these techniques improves
ing areas. Non-invasive techniques have shown variable/poor the success of the composite resin restorations substantially
success rates (Fragelli et al. 2015; Linner et al. 2020) but the (Sonmez and Saat 2017; de Souza et al. 2017; Rolim et al.
atraumatic restorative technique has shown some promising 2021; Somani et al. 2021). Overall, multiple studies report
short-term results using a glass-ionomer hybrid restoration positive results but over a short follow-up period. Longer
(Grossi et al. 2018), or a high-viscosity GIC (Durmus et al. follow-up periods are necessary to substantiate this evi-
2021). These studies have however methodological flaws dence. In addition, significant heterogeneity between stud-
and further high-quality research is needed to understand ies existed as there were significant variations in the teeth
the true effectiveness of the atraumatic restorative technique, studied including the size and extent of the defects, along
and materials used, in MIH. with the presence or absence of atypical or typical carious
lesions.
Considerations affecting treatment in severe cases In severe
cases where breakdown has already occurred or a cavity Preformed metal crowns (PMC) are an inexpensive option
is present due to caries, a number of treatment options are with reported high success rates (Kotsanos et al. 2005;
available. Ultimately, when faced with this clinical sce- Koleventi et al. 2018; Oh et al. 2020). They have the addi-
nario, a decision needs to be made as to whether to restore tional advantage of maintaining the structural integrity of
or extract these teeth. Such a decision needs to take all the the tooth whilst alleviating symptoms of hypersensitivity,
factors noted in Table 6 into consideration. A recent study maintaining the occlusal contact and can be placed in one
highlighted how complex these decisions are with substan- visit making them ideal for use in teeth where multiple sur-
tial differences noted between and within a group of non- faces are involved. Prior to placement, clinical photography
specialists and specialists in paediatric dentistry (Taylor along with detailed clinical notes of the status of the tooth
et al. 2019). are essential, as once the crown is placed, it is impossible
Consideration should be given to the structure, chemical to assess the tooth without removing the crown and poten-
and mechanical properties of enamel in such severe cases tially causing further damage. Preparation of the tooth,
if restoration is to be chosen. A systematic review of 22 with occlusal and proximal reduction, is usually required to
studies of hypomineralised enamel identified an increase in achieve a good fit. The placement of orthodontic separators
porosity, a reduction in hardness and elasticity and a change prior to the treatment appointment can be used to create
in carbon–carbonate ratios when compared with normal the space required proximally, as this would diminish the
enamel (Elhennawy et al. 2017). Additionally, an increase need for interproximal tooth reduction. Nonetheless, it is still
in protein content of serum albumin and other proteins has important to warn patients about a change in occlusion in
13
the short-term. One study reported an increased periodontal use the least invasive option and extension of the restoration
pocket depth in the short-term (Koleventi et al. 2018). This to conserve the remaining tooth structure due to wider pulp
may not be of clinical significance, especially if PMCs are chambers, higher pulp horns and relatively shorter clinical
used as an interim measure prior to scheduled extraction. crowns in children (Dhareula et al. 2019). Most studies had
However, further research is needed to understand the effects relatively small sample sizes and short follow-up periods,
on the periodontium if they are to be used as a long-term therefore, further longer-term studies with larger samples
option. The use of the Hall technique (Innes et al. 2007) are needed to establish a definitive answer.
for these teeth has also been suggested, however, further
research is needed. Pulp therapy in compromised first permanent molars is well
documented, however, there is little evidence available spe-
Laboratory manufactured indirect restorations have been cifically in MIH-affected molars. A recent systematic review
studied more recently for MIH-affected molars. Like PMCs, on compromised first permanent molars found that partial
these have reported very high success rates and can also be and coronal pulpotomies have high success rates, in the short
used in cases where multiple surfaces or cusps are involved and long term, but there is limited evidence available for
and direct restorations would be inappropriate (Gaardmand conventional pulpectomy or regenerative techniques (Taylor
et al. 2013; Dhareula et al. 2018, 2019; Linner et al. 2020). et al. 2020). Clearly this is an area where further research is
Three main categories of these restorations have been needed, however, partial or coronal pulpotomies can be con-
reported: metal alloys, indirect composite and ceramic res- sidered a potential treatment option in MIH-affected molars.
torations. All require technique sensitive tooth preparation,
longer chair time and have an increased treatment cost. A Scheduled extractions are indicated for teeth with significant
temporary restoration may also be required in the interim breakdown, or for those that are pulpally involved or associ-
period prior to final fit, which should be completed under ated with a dental abscess or facial cellulitis. In severe cases,
rubber dam. They are generally placed supra-gingivally and consideration should also be given to the long-term progno-
therefore less likely to have an impact on the periodontium sis of the tooth, the likelihood of repeated dental interven-
when compared to PMCs. Removal of all hypomineral- tions and the psychological impact on the child (Jälevik and
ised enamel is recommended to ensure appropriate bonding Klingberg 2012). Extraction may be the best option in these
to clinically sound enamel. Metallic onlays are used for their cases but complete spontaneous space closure is not guaran-
superior wear resistance, strength, retention and durability, teed, even if performed at the ideal time of 8–10 years of age
whilst materials such as gold can be placed in thin section (Ashley and Noar 2019). Three studies have reported vari-
(Harley and Ibbetson 1993; Zagdwon et al. 2003; Gaard- able success rates, in terms of spontaneous space closure,
mand et al. 2013; Dhareula et al. 2019;). Indirect composite when MIH-affected molars are extracted (Mejare et al. 2005;
onlays are a more aesthetic option and often require less Jälevik and Möller 2007; Oliver et al. 2014). These results
preparation due to their adhesive properties (Dhareula et al. are similar to those seen following extraction of MIH- and
2019). Furthermore, they can be easily repaired but do have non-MIH-affected molars of poor prognosis (Eichenberger
a poorer wear resistance. Ceramic restorations are an aes- et al. 2015). This more radical approach appears also cost-
thetic option with good strength and wear resistance noted effective compared to repeated restorative treatments, but
but require greater tooth preparation (Linner et al. 2020). there are no studies evaluating this parameter. To ensure
Studies comparing the three types of indirect restorations, the best possible outcome, orthodontic and radiographic
and PMCs, have found that all are successful, therefore, one evaluation is advised prior to scheduled extraction (Bru-
technique or material cannot be recommended over another sevold et al. 2021). An assessment of the child’s underlying
(Koch and Garcia-Godoy 2000; Zagdwon et al. 2003; malocclusion, any hypodontia, the presence or absence of
Dhareula et al. 2019). Consideration needs to be given to crowding, the presence of the third permanent molar and
Table 7 Factors to be At patient level At oral level At tooth level

considered for appropriate
treatment planning of anterior Age of patient Number of opacities Colour of opacity
teeth
Medical history DMFT Size of opacity
Ability to cooperate Developmental stage Depth of opacity
Psychological impact of dental appearance on Presence/absence of sensitivity
patient (e.g. bullying at school)
Access to specialist dental care Presence/absence of post-
eruptive breakdown
13
the dental developmental stage of the child are required to to enamel microhardness produced are still unpredictable
aid the decision-making process (Ashley and Noar 2019). (Crombie et al. 2014; Kumar et al. 2017) as resin infiltration
depth is inconsistent and variable depending partly on pre-
b. Treatment of anterior teeth treatment protocols (Natarajan et al. 2015). However, since
these lesions are usually located in non-stress surfaces, the
Appropriate treatment decisions for anterior teeth alteration in microhardness should not affect the longevity
must take into consideration several factors, as shown in of the treatment.
Table 7.
Other non-invasive/micro-invasive treatment options Whilst
General considerations Discoloured anterior teeth can have there are no studies specifically on MIH-affected incisors,
a considerable psychosocial impact on children (Rodd et al. previous research on external bleaching and the etch-bleach-
2011). Following treatment, an improvement in children’s seal technique for anterior opacities suggests that these may
overall health and oral health-related quality of life has been also be viable treatment options.
shown (Hasmun et al. 2020). A conservative approach is
important in children due to the large pulp chambers, high The etch-bleach-seal technique is a minimally invasive
pulp horns, and immature gingivae. Furthermore, a mini- technique that can be used to remove yellow–brown stains
mally invasive approach allows conservation of tooth struc- (Wright 2002; Prud'homme et al. 2017), although its effec-
ture for future restorative options. For children with poor tiveness has been questioned in MIH (Gandhi et al. 2012).
oral hygiene, cariogenic diets and multiple carious teeth, The tooth is bleached with 5% sodium hypochlorite for up to
cosmetic treatment should be deferred until an improvement twenty minutes, followed by application of 37% phosphoric
is demonstrated and carious teeth treated. There are very few acid etchant and clear resin sealant.
studies that are focussed on MIH-affected incisors with vari-
able success rates reported. Consequently, recommendations External bleaching is another non-invasive option that can
for a particular approach cannot be made. Additionally, due be used in adolescents to camouflage white opacities by
to the variability of opacities and discolouration, a combina- increasing the overall whiteness of the teeth. It is available as
tion of techniques may be necessary. The use of rubber dam hydrogen peroxide (up to 6%) or carbamide peroxide (10%
isolation, clinical photography before and after treatment in or 16%) gels used in custom-made trays. Its use by clinicians
addition to an explanation of the limitations of treatment, is in Europe varies (Monteiro et al. 2020). Side effects include
necessary for all options. gingival irritation and sensitivity, and these should be con-
sidered seriously particularly when used in younger children.
Microabrasion with either 18% hydrochloric acid or 37% Currently, the EU (Directive 2011/84/EU of the European
phosphoric acid followed by casein phosphopeptide-amor- Commission, October, 29th 2011) restricts tooth whitening
phous calcium phosphate (CPP‑ACP) remineralizing agent agents to 0.1% hydrogen peroxide in children, a clinically
appears to be effective for improving the aesthetic appear- ineffective concentration (Griffiths and Parekh 2021).
ance of whitish creamy opacities (Bhandari et al. 2019). A
pumice slurry or silicon carbide abrasive paste may be used. Composite restorations, with or without the removal of
It is a minimally invasive approach, only removing when enamel can mask opacities of all colours and replace areas
used appropriately, the surface 100–200 μm of enamel. As where breakdown has occurred (Welbury 1991). Deeper
such, it is not suitable for deeper opacities (Wong and Winter opacities may require removal of enamel, but this should
2002). be performed as conservatively as possible due to the pulp
anatomy of immature incisors. Thus, an opaquer may be
Resin infiltration, with a 15–20% hydrochloric acid etchant, required in specific cases, prior to composite being placed,
ethanol and TEGDMA monomer infiltrant has been sug- to mask any yellow–brown discolouration without extensive
gested for all types of opacities (Kim et al. 2011; ElBaz enamel removal. Over time, marginal staining, wear, and
and Mahfouz 2017; Bhandari et al. 2018). It is a minimally fracture can occur and long-term maintenance of composite
invasive option and simple technique, that aims to improve restorations is required (Welbury 1991; Wray and Welbury
the translucency, optical properties and overall colour 2008).
of affected incisors (Crombie et al. 2014). Enhanced oral
hygiene practices are essential as infiltrated enamel is more A combination of treatment approaches may be the ideal
susceptible to staining (Ceci et al. 2017). The technique future solution for MIH-affected anterior teeth. A recent
seems to be a feasible option for colour masking of whitish study used a combination of approaches (microabra-
opacites in MIH, although there is no strong evidence sup- sion, resin infiltration, external bleaching and composite
porting this (Borges et al. 2017). Additionally, the changes
13
restoration) with each participant having an individual- However, despite these measurement challenges, topical
ised approach depending on their clinical need; the results CPP-ACP does seem to improve mineralisation due to the
revealed that simple, minimally invasive treatments can stabilisation of calcium and phosphate ions by casein phos-
provide good clinical and psychosocial outcomes (Has- phopeptide, a protein which carries these ions in the form
mun et al. 2020). In addition, there are some case reports of amorphous calcium phosphate (Baroni and Marchionni
demonstrating these combined approaches (Attal et al. 2011; Biondi et al. 2017; Bakkal et al. 2017). As casein is
2014; Prud'homme et al. 2017), however, further research a milk protein derivative, CPP-ACP should be avoided in
is needed to investigate the efficacy and long-term outcomes those allergic to milk proteins. Although CPP-ACFP and
of undertaking such combined treatment options in MIH- sodium fluoride with and without tricalcium phosphate have
affected anterior teeth. shown to remineralise affected enamel (Restrepo et al. 2016;
Bakkal et al. 2017; Biondi et al. 2017), there is insufficient
c. Management of hypersensitivity and remineralisa- evidence to recommend it for this purpose. Even though
tion insufficient evidence exists for the use of fluoride varnish
in remineralisation and desensitisation, it should still be
Hypersensitivity can impact mastication, oral hygiene used in children with MIH for caries prevention due to their
practices and quality of life. Several options for manage- increased risk.
ment are available and include casein phosphopeptide-amor- In general, and regarding treatment of MIH-affected
phous calcium phosphate (CPP-ACP), casein phosphopep- teeth, there is insufficient evidence to clearly suggest that
tide-amorphous calcium fluoride phosphate (CPP-ACFP), any one of the above-detailed options is superior in the long
sodium fluoride varnish 5–6% with and without tricalcium term. Additionally, the majority of studies were rated at
phosphate, 8% arginine and calcium carbonate paste, ozone moderate or high risk of bias with significant heterogeneity
or low-level laser therapy. A recent systematic review preventing meta-analysis of the results in a recent systematic
reported that all studies which looked at the management of review (Somani et al. 2021).
hypersensitivity showed a reduction post treatment, but none
of these interventions can be recommended due to the mod- GRADE rating for the quality of evidence
erate–high risk of bias in the studies, short follow-up times and strength of recommendations of the treatment
and small sample sizes (Somani et al. 2021). Similarly, the studies in MIH teeth
studies investigating remineralisation in MIH-affected teeth
had comparable limitations (Somani et al. 2021). Remineral- Using the GRADE system, the rating for quality of evidence
isation is difficult to measure, with an increase in laser fluo- and strength of recommendation regarding treatment options
rescence or quantitative light fluorescence readings reported for MIH molars and incisors in addition to remineralisation
in studies often not translating to a clinical improvement. and sensitivity reduction options for MIH-affected teeth are
Table 8 GRADE rating for quality of evidence and strength of recommendation regarding treatment options for MIH molars
Interventions for molars No. of No. of GRADE of Strength of
studies restorations / evidence Recommen-
teetha quality dation
Fissure sealants, applied with an adhesive, can be used in mild cases in fully erupted 3 184 Moderate Strong
molars
GIC restorations using a non-invasiveb approach may be used as in cases where the 5 333 Moderate Conditional
child cannot co-operate for conventional treatment
Composite resin restorations placed under rubber dam isolation, using an invasive b 8 793 Moderate Strong
approach can be used as a restorative option in mild/severe cases
Non-invasive b composite restorations should not be placed 2 189 Moderate Strong
The use of self-etch, total etch or deproteinisation with sodium hypochlorite is unlikely 3 137 Moderate Strong
to make a difference to the retention rate of a composite restoration
PMCs can be placed in severe cases 3 88 Moderate Strong
Laboratory manufactured restorations using an invasive approach can be used as a 4 132 Moderate Conditional
restorative option in severe cases
Good space closure can be achieved spontaneously following extraction of affected 3 189 Moderate Conditional
molars
a
Drop-outs have not been excluded as it was not possible to ascertain the number in all of the studies due to mixed data
b
Non-invasive—preservation of affected enamel; invasive—removal of all hypomineralised enamel to achieve margin on clinically sound enamel
13
Table 9 GRADE rating for Interventions for Incisors No. of studies No. of teeth GRADE of evi- Strength of
quality of evidence and strength dence quality Recommenda-
of recommendation regarding tion
treatment options for MIH
incisors Resin infiltration can be used 3 66 Low Conditional
to improve the appearance of
affected incisor teeth
Microabrasion can be used to 1 43 Very low Conditional
improve the appearance of
affected incisor teeth
Table 10 GRADE rating for quality of evidence and strength of recommendation regarding remineralisation and sensitivity reduction options for
MIH-affected teeth
Interventions for remineralisation No. of studies No. of teeth GRADE of Strength of

evidence Recommen-
quality dation
Topical CPP-ACP can be used to remineralise affected teeth 3 61 Moderate Conditional

Topical CPP-ACFP/NaF 4–5% with and without tricalcium phosphate can be used 3 88 Very low Conditional
to remineralise affected teeth
Interventions for reduction of hypersensitivity
Topical CPP-ACP/CPP-ACFP/NaF 5–6% with and without tricalcium phos- 4 382 Low Conditional
phate/8% arginine and calcium carbonate/ozone/laser can be used to reduce the
symptoms of hypersensitivity in affected teeth
shown in Tables 8, 9 and 10, respectively. Details of the Clinical practice guidance for treatment
implementation of all criteria regarding the included studies approach for MIH teeth
are shown in the supplement as Appendix 2.
As this Policy Document was prepared to facilitate the
clinician’s decision-making, a diagrammatic summary of
possible factors interacting for each treatment modality
Fig. 4 Diagrammatic manage-

ment summary according to
factor-severity for MIH-affected
molars. Severity is incremen-
tally increased from the left to
the right. To select the appropri-
ate option, the block with the
most severe sign/symptom
should dominate the choice
13
Fig. 5 Diagrammatic manage-

ment summary according to
factor-severity for MIH-affected
incisors. To select the appro-
priate option, the block with
the most severe sign/symptom
should dominate the choice
according to the severity of the condition at a particular e. The EAPD strongly endorses the use of all available
dental age, is shown in Figs. 4 and 5. They were con- treatment tools for the treatment of MIH teeth, keeping
structed using sign/symptom-severity blocks to help the in mind the necessity for painless and effective treat-
clinician to choose the appropriate treatment options. ment plan and the well-being of the paediatric patient at
dental, oral, medical and social levels.
Conclusion
Future research recommendations
a. MIH is becoming an important public health issue with
global prevalence of 12.9%–14.2% being reported. How- a. Regarding the aetiology of MIH, future clinical studies
ever, these figures may be an underestimation. should be prospective if systemic aetiological factors are
b. The globally established EAPD diagnostic criteria and to be evaluated, whilst genetic studies should focus on
the recent efforts for unified and convenient charts for the genes and gene–environment interactions that regu-
epidemiological studies will further help such studies in late the genetic predisposition to MIH.
the future. b. Regarding the treatment of MIH, future research should
c. The aetiology of MIH is better understood, as it clearly focus on further improvements in adhesion, the use of
follows a multi-factorial model that in some instances new materials and the assessment of novel more mini-
may be the result of environmental–gene interactions. mally invasive techniques. Furthermore, to address the
Systemic medical factors, such as perinatal hypoxia, pre- psychosocial and economic impacts of MIH treatments,
maturity and other hypoxia-related perinatal problems, a holistic management strategy should be adopted.
including caesarean section appear to multiply the risk
of having MIH. Infant and childhood illnesses, are also
linked with MIH, while fever and antibiotic use, which Supplementary Information The online version contains supplemen-
tary material available at https://doi.org/10.1007/s40368-021-00668-5.
may be considered as consequences to illnesses have
been also been implicated. Acknowledgements The authors wish to sincerely thank the Board of
The role of genetic predisposition and epigenetic the European Academy of Paediatric Dentistry for entrusting them with
influences is becoming clearer, and may be regarded as the development of the updated Policy Document on the ‘Best Clini-
the key piece of information currently missing to truly cal Practice guidance for clinicians dealing with children presenting
with molar incisor hypomineralisation (MIH)’. Special thanks should
understand MIH aetiology. be attributed to the Chair and the members of the EAPD Clinical
d. Successful preventive and treatment options have been Affairs Committee (Drs. Susan Parekh, Joana Monteiro, Sivaprakash
studied and identified for MIH-affected molars, with the Rajasakheran, Michal Sobczak, Rona Leith, Eirini Stratigaki, Vuokko
severity of the defect and the age of the patient often dic- Anttonen) who efficiently reviewed the draft document and suggested
useful corrections. In addition, Prof. David Manton made important
tating the chosen approach. The same cannot be said for suggestions during the preparation of the systematic reviews that were
anterior teeth. Despite an increase in the number of stud- the framework for the present updated Policy Document on MIH.
ies addressing the management of MIH-affected teeth, Finally, sincere thanks should also be given to all colleagues being
the evidence is still limited with conventional restorative involved with MIH research the last 10 years and have contributed
substantially to the further development of the evidence base of MIH.
options remaining the most common approach.
13
Funding The authors did not receive support from any organisation Bhandari R, Thakur S, Singhal P, Chauhan D, Jayam C, Jain T. In vivo
for the submitted work. comparative evaluation of esthetics after microabrasion and
microabrasion followed by casein phosphopeptide-amorphous
Availability of data/materials Please contact corresponding author. calcium fluoride phosphate on molar incisor hypomineralization-
affected incisors. Contemp Clin Dent. 2019;10(1):9–15. https://
doi.org/10.4103/ccd.ccd_852_17.
Code availability Not applicable.
Biondi AM, Cortese SG, Babino L, Fridman DE. Comparison of min-
eral density in molar incisor hypomineralization applying fluo-
Declarations ride varnishes and casein phosphopeptide-amorphous calcium
phosphate. Acta Odontol Latinoam. 2017;30(3):118–23.
Conflict of interest The authors have no conflicts of interest to declare. Borges AB, Caneppele TMF, Masterson D, et al. Is resin infiltration an
effective esthetic treatment for enamel development defects and
Ethical approval No applicable. white spot lesions? A systematic review. J Dent. 2017;56:11–8.
https://doi.org/10.1016/j.jdent.2016.10.010.
Consent Not applicable. Brusevold IJ, Kleivene K, Grimsøen B, et al. Extraction of first perma-
nent molars severely affected by molar incisor hypomineralisa-
tion: a retrospective audit. Eur Arch Paediatr Dent. 2021. https://
Open Access This article is licensed under a Creative Commons Attri- doi.org/10.1007/s40368-021-00647-w.
bution 4.0 International License, which permits use, sharing, adapta- Bullio Fragelli CM, Jeremias F, Feltrin de Souza J, Paschoal MA, de
tion, distribution and reproduction in any medium or format, as long Cássia Loiola Cordeiro R, Santos-Pinto L. Longitudinal evalua-
as you give appropriate credit to the original author(s) and the source, tion of the structural integrity of teeth affected by molar incisor
provide a link to the Creative Commons licence, and indicate if changes hypomineralisation. Caries Res. 2015;49(4):378–83. https://doi.
were made. The images or other third party material in this article are org/10.1159/000380858.
included in the article's Creative Commons licence, unless indicated Bussaneli DG, Restrepo M, Fragelli CMB, Santos-Pinto L, Jeremias
otherwise in a credit line to the material. If material is not included in F, Cordeiro RCL, et al. Genes regulating immune response and
the article's Creative Commons licence and your intended use is not amelogenesis interact in increasing the susceptibility to molar-
permitted by statutory regulation or exceeds the permitted use, you will incisor hypomineralization. Caries Res. 2019;53(2):217–27.
need to obtain permission directly from the copyright holder. To view a https://doi.org/10.1159/000491644.
copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. Bussaneli DG, Vieira AR, Santos-Pinto L, et al. Molar-incisor
hypomineralisation: an updated view for aetiology 20 years
later. Eur Arch Paediatr Dent. 2021. https://doi.org/10.1007/
s40368-021-00659-6.
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Authors and Affiliations
N. A. Lygidakis1 · E. Garot2,3,4 · C. Somani5 · G. D. Taylor6 · P. Rouas2,3,4 · F. S. L. Wong5
1 4
Private Paediatric Dental Clinic, 2 Papadiamantopoulou Univ. de Bordeaux, PACEA, UMR 5199, Pessac, France
Street, 11528 Athens, Greece 5
Paediatric Dentistry, Institute of Dentistry, Barts and The
2
Univ. de Bordeaux, UFR des Sciences Odontologiques, London School of Medicine and Dentistry, Queen Mary
Bordeaux, France University of London, London, UK
3 6
CHU de Bordeaux, Pôle médecine et chirurgie School of Dental Sciences, Faculty of Medical Sciences,
bucco-dentaire, Pellegrin, Bordeaux, France Newcastle University, Newcastle upon Tyne, UK
13

MIH Best Practice

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European Archives of Paediatric Dentistry

Best clinical practice guidance for clinicians dealing with children

Received: 12 September 2021 / Accepted: 22 September 2021

The European Academy of Paediatric Dentistry (EAPD) was

Table 1 GRADE ratings and their interpretation

Table from the GRADE Handbook, available at: http://​gdt.​guide​lined​evelo​pment.​org/​app/​handb​ook/​handb​ook.​html#h.​9rdbe​lsnu4​iy

Table 2 Strengths of recommendation for patients and clinicians

Terminology and diagnosis of MIH Diagnostic criteria

Table 4 Description of severity Severity level Signs and symptoms

0 = No visible enamel defect.

0 = No visible enamel defect.

Fig. 3 World map of MIH

Table 5 GRADE quality of evidence of included studies related to aetiology

Allergies 6 2432 518 Low

b. Perinatal period diseases, pneumonia and asthma, were also found to be

Appropriate treatment decisions for posterior teeth should

Age of patient Number of affected teeth Size of defect

Table 7 Factors to be At patient level At oral level At tooth level

Interventions for remineralisation No. of studies No. of teeth GRADE of Strength of

Topical CPP-ACP can be used to remineralise affected teeth 3 61 Moderate Conditional

Fig. 4 Diagrammatic manage-

Fig. 5 Diagrammatic manage-

Authors and Affiliations

N. A. Lygidakis1 · E. Garot2,3,4 · C. Somani5 · G. D. Taylor6 · P. Rouas2,3,4 · F. S. L. Wong5

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Table from the GRADE Handbook, available at: http://gdt.guidelinedevelopment.org/app/handbook/handbook.html#h.9rdbelsnu4iy