Journal of Dentistry 60 (2017) 1–7

Contents lists available at ScienceDirect

Journal of Dentistry
journal homepage: www.intl.elsevierhealth.com/journals/jden

Review article

Developmental defects of enamel and dental caries in the primary

dentition: A systematic review and meta-analysis
Francine S. Costaa , Ethieli R. Silveirab , Gabriela S. Pintoc , Gustavo G. Nascimentod,
William Murray Thomsone , Flávio F. Demarcoa,*
a
Postgraduate Program in Dentistry and Postgraduate Program in Epidemiology, Federal University of Pelotas, Pelotas, Brazil
b
Postgraduate Program in Dentistry, Federal University of Pelotas, Pelotas, Brazil
c
College in Dentistry, Faculdade Especializada na Área de Saúde do Rio Grande do Sul, Passo Fundo, Brazil
d
Federal University of Pelotas and Section of Periodontology, Department of Dentistry and Oral Health, Aarhus University, Aarhus, Denmark
e
Sir John Walsh Research Institute, University of Otago, Dunedin, New Zealand

A R T I C L E I N F O A B S T R A C T

Article history: Objectives: This systematic review and meta-analysis evaluated the association between developmental
Received 7 December 2016 defects of enamel and dental caries in the primary dentition.
Received in revised form 20 March 2017 Sources: Electronic searches were performed in PubMed, Web of Knowledge, Scopus and Scielo for the
Accepted 22 March 2017
identification of relevant studies.
Study selection: Observational studies that examined the association between developmental defects of
Keywords: enamel and dental caries in the deciduous dentition were included. Additionally, meta-analysis, funnel
Developmental defects of enamel
plots and sensitivity analysis were employed to synthesize the available evidence. Multivariable meta-
Dental caries
Primary dentition
regression analysis was performed to explore heterogeneity among studies.
Deciduous teeth Data: A total of 318 articles were identified in the electronic searches. Of those, 16 studies were included
Pediatric dentistry in the meta-analysis. Pooled estimates revealed that children with developmental defects of enamel had
higher odds of having dental caries (OR 3.32; 95%CI 2.41–4.57), with high heterogeneity between studies
(I2 80%). Methodological characteristic of the studies, such as where it was conducted, the examined
teeth and the quality of the study explained about 30% of the variability. Concerning type of defect,
children with hypoplasia and diffuse opacities had higher odds of having dental caries (OR 4.28; 95%CI
2.24–8.15; OR1.42; 95%CI 1.15–1.76, respectively).
Conclusions: This systematic review and meta-analysis demonstrates a clear association between
developmental defects of enamel and dental caries in the primary dentition.
© 2017 Elsevier Ltd. All rights reserved.

1. Introduction (hypoplasia) or qualitative ones (demarcated or diffuse opacities

Enamel developmental defects (EDD) occur due to biological
imbalances that affect the cells involved in enamel formation and
maturation, depending of the type of defect [1]. The influence of
these defects on the risk of tooth decay is ongoing, especially in
respect of biofilm retention [2], and its plausibility should be
considered with respect to the types of defects involved. Enamel
defects can be broadly categorised as quantitative defects
* Corresponding author at: School of Dentistry/Federal University of Pelotas,
Gonçalves Chaves Street 457, 5th floor, Pelotas, RS, Brazil.
E-mail addresses: francinesct@gmail.com (F.S. Costa), ethieli2@gmail.com
(E.R. Silveira), gabipinto@gmail.com (G.S. Pinto),
gustavo.gnascimento@hotmail.com (G.G. Nascimento),
murray.thomson@otago.ac.nz (W.M. Thomson), ffdemarco@gmail.com
(F.F. Demarco).
), with opacities the most prevalent type [3–5]).
Reported prevalence estimates for any enamel defect in the
deciduous dentition range from 3.9% to 81.5% [6–10]. Some EDD
may predispose the tooth to dental caries due to structural defects
in the tooth surface [1,6]. In deciduous teeth, the affected enamel
has a lower mineral content and may predispose to plaque
accumulation and subsequent carious activity [7]. The association
between DDE and caries may be underestimated, however, since
the carious lesion may have masked the initial, undiagnosed
enamel defect [11].
Dental caries in primary teeth is caused by a complex
interaction among environmental, maternal, and child factors
[12]. The treatment of dental diseases exacts a high economic cost
at both individual and health system levels [13]. Untreated dental
caries in primary teeth is the main cause of dental pain among
children [14]. It also impacts on dental fear and avoidance of dental

http://dx.doi.org/10.1016/j.jdent.2017.03.006
0300-5712/© 2017 Elsevier Ltd. All rights reserved.
2 F.S. Costa et al. / Journal of Dentistry 60 (2017) 1–7
treatment [15]. Dental caries and enamel defects can negatively
affect the oral health related quality of life of both children and
their parents [16,17].
A recent systematic review showed that EDD were associated
with a higher chance of having dental caries [18], but there is a lack
of consensus about the association between EDD and dental caries
in primary teeth. Methodological differences (such as the teeth
examined and the method used for EDD detection) contribute to
the conflicting findings [8]. Accordingly, the aim of the present
study was to systematically review the literature in order to
evaluate the association between development defects of enamel
and dental caries experience in the primary dentition.
2. Methods
The research question behind this systematic review was: Is
there an association between developmental defects of enamel and
dental caries in primary dentition?
Original observational studies that investigated the association
between developmental defects of enamel (EDD) and primary
dentition dental caries among a representative sample of children
were included. Additionally, EDD and dental caries experience
must have been assessed by clinical examination. The case
definitions for DDE and dental caries were accepted as declared
by the authors.
Animal studies, letters to the editor, reviews and studies with
explicit convenience sample (institutionalized/hospitalized indi-
viduals, vulnerable population, sample selection performed
according to the researcher interest) were excluded. Studies in
languages other than English, Spanish or Portuguese were also
excluded.
Electronic searches were conducted to identify the published
literature from 1945 to November 2016 in databases including
PubMed, Web of Knowledge, Scopus and Scielo for the identifica-
tion of relevant studies. An initial search was conducted on
PubMed with the following MeSH and free terms: (“Dental Enamel
Hypoplasia”[Mesh] OR “Enamel Defects”[all] OR “Developmental
Fig. 1. Flowchart of selection process.
Defects of Enamel”[all] OR “Dental Hypoplasia”[all] OR “Opacitie-
s”[all] OR “Enamel Hypoplasia”[all]) AND (“Dental Caries”[Mesh]
OR “Tooth Decay”[all] OR “Tooth Cavity”[all]) AND (“Tooth,
Deciduous”[Mesh] OR “Primary Tooth”[all] OR “Primary Dentitio-
n”[all] OR “Deciduous Tooth”[all] OR “Deciduous Teeth”[all] OR
“Primary Teeth”[all])”. No language restrictions were applied
within the search.
All papers were managed using the software EndNote X7
(Thomson Reuters, New York, NY, US). Duplicate papers were
excluded. Titles and abstracts were screened based on the
aforementioned criteria independently by two reviewers (ERS
and FSC). The screened lists were compared and, in case of any
disagreement, a consensus was reached through discussion. After
initial screening of titles and abstracts, full articles were evaluated
by the same two reviewers. In addition to the electronic search, the
reviewers also undertook a hand search in the references list of
each included study. Structured data collection worksheets were
employed for the assessment of each publication. This systematic
review followed the PRISMA statement for reporting [19].
The Critical Appraisal Checklist described by the Joanna Briggs
Institute [20] was used for quality assessment of the selected
studies. The 10-item checklist is available as Supplemental
Material. Reviewers answered ‘Yes’, ‘No’ or ‘Unclear’ for each item.
To categorize studies according to quality, an overall score for each
study was calculated based on the number of ‘Yes’ answers, so that
scores could range from 0 to 10. Finally, studies were categorised
according to their scores: low quality [score between 0 and 3];
moderate quality [4–6]; or high quality [7–10] [21,22]. The same
two reviewers conducted the quality assessment, and disagree-
ments were resolved by discussion until agreement.
Relevant data were extracted from the selected articles broadly
under the categories of: study description (setting, sample and
design); EDD and dental caries measure employed; results on
association; and methodological quality. Furthermore, in order to
conduct the meta-analysis, crude and adjusted association
measures (Relative Risk/Odds Ratio) with respective 95% Confi-
dence Intervals (95%CI) were recorded. The original authors were
 F.S. Costa et al. / Journal of Dentistry 60 (2017) 1–7 3

contacted when further clarifications regarding the study meth-
odology or results were required. Data were extracted by two
reviewers (ERS and FSC) independently using pre-piloted data
extraction forms. In case of any disagreements, discussions were
held to resolve and reach consensus. All stages of this systematic
review were supervised by a third reviewer (GGN) with expertise
in systematic review methodology.
A meta-analysis was conducted to address the review question.
Where adjusted results were available, they were included;
otherwise, crude result estimates were considered. Combined
results were presented as a pooled odds ratio. Effect estimates
were appropriately converted to odds ratios when necessary [23].
When studies reported more than one result for the association,
only the lowest value was included in the analysis. In longitudinal
studies, only the most recent result was used in the meta-analysis.
Pooled odds ratio was estimated using fixed- and random-effect
models. In the event of heterogeneity (Chi-square P-value<0.05 or
I2>50%), the random-effect model was preferred [24]. Sensitivity
analyses were further conducted to estimate and verify the
influence of each study on the pooled results. A Funnel plot and the
Egger test were used to test for any potential publication bias.
Meta-regression analysis was undertaken in order to identify
possible sources of heterogeneity among studies. Meta-regression
analyses were employed with random-effects model using
aggregate-level data. Our choice was based on the possibility of
“residual heterogeneity”, which could remain even when all
heterogeneity in the model is explained [25]. Methodological
characteristics were included in a multivariable regression model.
Backward stepwise approach was used for variable selection.
Variables with a P-value < 0.20 were in the final model.
Additionally, subgroup analysis was performed according to each
methodological variable included in the final adjusted model. All
analyses were performed using Stata 13.1 using the macros metan,
metafunnel, metainf and metareg (StataCorp, College Station, TX,
USA).
3. Results
Electronic searches revealed 332 hits. After removing 152
duplicates, 180 articles were considered for title and abstract
screening. Forty-one were included for full text evaluation and,
from those, 23 were excluded (Supplementary table) after full text
assessment. Consequently, 18 studies fulfilled the inclusion criteria
for this systematic review, but 16 studies were included in the
meta-analysis (Fig. 1). Table S1 displays the excluded studies, and
the main reason for exclusion.
The main findings of the included studies were summarised in a
supplementary table (Table S2). The sixteen studies included in the
analysis comprised a total of 11,126 children. Twelve studies had
been conducted in low-middle-income countries, with the other
four studies in high-income countries. Table 1 presents data on the
direction of association between enamel defects and dental caries.
Children with a developmental defect of enamel had three times
higher odds of having dental caries experience (OR 3.32; 95%CI
2.41–4.57) (Fig. 2). The Egger test revealed a small study effect
(p = 0.025). The evaluation of publication bias was demonstrated in
a funnel plot (Fig. 3). Sensitivity analysis showed that the omission
of any study would not modify the association between DDE and
dental caries (Fig. 4). The geographic region where the study was
conducted, the examined teeth, the quality of the study and
adjustment for socioeconomic information explained about 38% of
the variability.
Table 2 summarizes the results of the subgroup analysis by the
aforementioned methodological characteristics. The magnitude of
the association was overestimated in studies that: (a) did not
perform adjusted analysis; (b) examined all teeth; (c) had been
conducted in the Middle-East; or (d) did not adjust for
socioeconomic information (Table 2).
Concerning the type of enamel defect, three studies were
included in the meta-analysis to evaluate the odds of dental caries
associated with diffuse opacities; six studies examined demarcat-
ed opacities; and nine evaluated hypoplasia. Children with diffuse
opacities and with hypoplasia had higher odds of having dental
caries experience (OR 1.42; 95%CI 1.15–1.76; OR 4.28; 95%CI 2.24–
8.15, respectively). The presence of demarcated opacities was not
associated with dental caries (OR 2.62; 95%CI 0.85–8.12), but when
only studies that evaluated molar hypomineralization were
included, the pooled effect was significant (OR 3.11; 95% CI
1.75–5.51).
Table 3 summarizes the outcome of the meta-regression and
subgroup analysis according to the methodological characteristics
of the studies evaluating the association between enamel
hypoplasia and dental caries. The magnitude of the association
was underestimated in studies that: (a) did not perform
adjustment for socioeconomic information; (b) examined only
index teeth; or (c) did not use the DDE index recommended by the
FDI (Table 3).

Table 1
Studies included in the systematic review and the direction of association between enamel defects and dental caries in primary dentition (n = 18).

Author/Year/Setting Adjustment Direction of association

Alkhtib et al., 2016 [26] – Qatar No 0
Corrêa-Faria et al., 2015 [10] – Brazil Yes +
Yadav et al., 2015 [27] – India No +
Ghanim et al., 2013 [5] – Iraq No +
Basha and Swamy, 2012 [28] – India Yes +
Masumo et al., 2013 [8] – Uganda, Tanzania Yes + Uganda/0 Tanzania
Targino et al., 2011 [29] – Brazil No +
Zhou et al., 2011 [30] – China No 0
Elfrink et al., 2010 [31] – Netherlands No +
Farsi, 2010 [4] – Saudi Arabia No +
Hong et al., 2009 [32] – USA Yes +
Hoffmann et al., 2007 [3] – Brazil No +
Oliveira et al, 2006 [6] – Brazil Yes +
Casanova-Rosado et al., 2005 [33] – Mexico Yes +
Segovia-Villanueva et al., 2005 [34] – Mexico No +
Li et al., 1996 [35] – China No +
Kanchanakamol et al., 1996 [36] – Thailand No +
Pascoe et al., 1994 [37] – Australia No +

+ Positive association between enamel defects and dental caries; 0 no association founded.
4 F.S. Costa et al. / Journal of Dentistry 60 (2017) 1–7

Fig. 2. Meta-analysis of studies included (unadjusted and adjusted analysis).

4. Discussion

The meta-analysis is taken as a robust source of evidence

because it amplifies the statistical power and undertakes a quality
assessment of included studies. Consistent findings have been
observed in individual studies, and this study demonstrates with
greater robustness that children with EDD had higher odds of
having dental caries in the primary dentition. Some hypotheses are
considered to explain the association between EDD and dental
caries. At the tooth level, developmental defects of enamel seem to
be associated with greater plaque accumulation. Moreover, dental
hygiene and plaque removal are impaired in severe cases of EDD
[2].
Some limitations of our study should be considered. First, some
studies included in the review were of low methodological quality,
and this might have affected the pooled estimate, reflecting in wide
confidence intervals in the meta-estimates. However, meta-
regression analysis showed no influence of methodological quality
on the variability between studies. Second, meta-regression
analysis performed for enamel hypoplasia included only nine
studies. Since meta-regression is recommended where there are
more than 10 studies, we cannot be certain whether other
methodological variables included in the analytical model could be
Fig. 3. Funnel plot of publication bias.
 F.S. Costa et al. / Journal of Dentistry 60 (2017) 1–7 5

Fig. 4. Sensitivity analysis of included studies.

sources of bias, or whether the statistical power to identify those
was lacking. Third, most of the studies used a cross-sectional
design, precluding estimation of the long-term risk of dental caries
in children with EDD. Finally, the Egger test and the funnel plot
revealed a degree of publication bias. We used different strategies
in order to reduce publication bias, such as a hand search in the
reference list of all included studies.
Concerning the strengths of the study, we included only
population-based studies with representative samples. Addition-
ally, the use of sensitivity analysis, subgroup analysis and meta-
regression further contributes to the robustness of our findings.
Moreover, to the best of our knowledge, this is the first systematic
investigation into the association between enamel defects and
dental caries in the primary dentition.
The meta-regression analysis demonstrated that the adjust-
ment for confounders partially explained the heterogeneity among
studies. Low socioeconomic status, birth conditions and nutrition-
al status in pregnancy are associated (even though by non-direct
paths) with both enamel defects and dental caries in children
[10,18,38–42]. Caries experience is greater in low-income families
[41,42]. Similarly, low socioeconomic status has been reported to
be a risk factor for EDD, along with conditions related to this status,
as childhood infections, low birth weight or poor nutrition in
pregnancy [8,9]. Thus, these factors should be considered relevant
confounders of this association.
Adjustment for these confounders should be undertaken when
studying the association between EDD and dental caries, as
demonstrated in a previous review [18]. Otherwise, estimates
might suffer from bias. Our findings show that pooled estimates

Table 2
Subgroup and meta-regression analysis of enamel development defects according to the methodological covariates.

Methodological characteristics N Pooled Odds Ratioa 95%CI

Adjusted Analysis
No 9 3.60 2.14–6.04
Yes 8 2.82 2.13–3.72

Adjustment for socioeconomic information

No 10 3.88 2.34–6.42
Yes 7 2.64 2.11–3.31

Examined Teeth
All 8 4.48 2.52–7.97
Index teeth 6 2.94 2.15–4.00

Geographic Location
Americas 7 3.18 2.02–5.00
Asia/Oceania 5 3.06 1.92–4.88
Middle East 2 6.08 1.69–21.94
Europe 1 3.21 1.13–9.10
Africa 2 2.06 1.32–3.21

Heterogeneity Explained (R2)b: 38.2%

a
Odds ratio for dental caries in children with EDD compared to those without in subgroups of studies according to methodological characteristics.
b
Adjusted R2 of the final meta-regression model.
6 F.S. Costa et al. / Journal of Dentistry 60 (2017) 1–7
Table 3
Subgroup and meta-regression analysis of enamel hypoplasia according to the methodological covariates.
Methodological characteristics
Adjustment for socioeconomic information
No
Yes
Examined Teeth
All
Index teeth
DDE Index
DDE Index (FDI)
Modified DDE Index (FDI) plus others index
Heterogeneity Explained (R2)b : 67.9%
a
Odds ratio for dental caries in children with enamel hypoplasia compared to those without in subgroups of studies according to methodological characteristics.
b
Adjusted R2 of the final meta-regression model.
from studies which had been performed without adjustment
tended to overestimate the magnitude of the association between
EDD and dental caries in primary teeth. As with the permanent
dentition, enamel defects and dental caries in the primary
dentition are influenced not only by biological aspects but also
by contextual characteristics [18].
The number of examined teeth was identified as a source of
heterogeneity among studies. Our findings suggest that the
examination of index teeth only might have underestimated any
association. Future studies should be aware of this relevant
methodological aspect. The geographic location where the study
was conducted was also important, with Middle-Eastern studies
showing stronger associations as had been shown with higher
prevalence of dental erosion [43]. This is likely due in part to the
greater prevalence of early childhood caries in those countries.
Even though a positive association was observed, these results
should be carefully interpreted. Wide confidence intervals reveal
the imprecision of such findings.
The defect-specific analysis showed that children with diffuse
opacities, hypoplasia or molar hypomineralization had higher odds
of having dental caries. Investigators should be aware of the
differences in etiology and presentation among the various enamel
defect types, and that they may have different degrees of
association with dental caries experience. This is reflected in our
findings, where demarcated opacities were not associated with
caries experience but diffuse opacities were. The latter finding is
somewhat counter-intuitive, given the well-documented negative
association between mild diffuse opacities and caries in the
permanent dentition. Given that diffuse opacities are a maturation
defect rather than a secretory one, and the lower mineral levels of
deciduous enamel, it may indeed be that such defects in the
primary dentition predispose it to caries [44].
Concerning to demarcated opacities, these defects were not
associated with dental caries and it is probably because are limited
and, in some cases, caries may mask the occurrence of this defect,
reducing the outcome on the exposed group. However, when were
analyzed studies that evaluated only molar hypomineralization,
children with these defects had three times higher odds of having
dental caries experience. Demarcated molar hypomineralisation is
a defect that according with the severity possibly progressing and
may increase the risk of developing carious lesion [5]. About
diffuse opacities, the findings should be also interpreted with
caution, as these defects can be considered fluorotic defects.
The findings from the systematic review and meta-analysis
clearly demonstrated an association between developmental
defects of enamel and dental caries in the primary dentition. A
preventive approach of dental caries and attention to children with
N Pooled Odds Ratioa 95%CI
6 3.75 1.56–9.24
3 5.59 2.17–14.40
3 7.66 1.08–54.58
6 3.54 1.85–6.76
3 9.02 (3.85–21.11)
6 3.31 (2.01–5.44)
enamel defects appears as a useful health promotion and public
health strategy. At the individual level, clinicians should be aware
that children with EDD could require more frequent visits to the
dental office in order to reduce the risk of dental caries.
Appendix A. Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.
jdent.2017.03.006.
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