1

Introduction

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 . The influence of these defects on the risk of tooth decay is ongoing, especially in respect of biofilm retention , and its plausibility should be considered with respect to the types of defects involved. Enamel defects can be broadly categorised as quantitative defects (hypoplasia) or qualitative ones (demarcated or diffuse opacities), with opacities the most prevalent type ).

Reported prevalence estimates for any enamel defect in the deciduous dentition range from 3.9% to 81.5% . Some EDD may predispose the tooth to dental caries due to structural defects in the tooth surface . In deciduous teeth, the affected enamel has a lower mineral content and may predispose to plaque accumulation and subsequent carious activity . The association between DDE and caries may be underestimated, however, since the carious lesion may have masked the initial, undiagnosed enamel defect .

Dental caries in primary teeth is caused by a complex interaction among environmental, maternal, and child factors . The treatment of dental diseases exacts a high economic cost at both individual and health system levels . Untreated dental caries in primary teeth is the main cause of dental pain among children . It also impacts on dental fear and avoidance of dental treatment . Dental caries and enamel defects can negatively affect the oral health related quality of life of both children and their parents .

A recent systematic review showed that EDD were associated with a higher chance of having dental caries , 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 . 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 individuals, 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 identification 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 Defects of Enamel”[all] OR “Dental Hypoplasia”[all] OR “Opacities”[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 Dentition”[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 .

The Critical Appraisal Checklist described by the Joanna Briggs Institute 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] . The same two reviewers conducted the quality assessment, and disagreements 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% Confidence Intervals (95%CI) were recorded. The original authors were contacted when further clarifications regarding the study methodology 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 . 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 I ² >50%), the random-effect model was preferred . 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 . 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).

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 individuals, 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 identification 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 Defects of Enamel”[all] OR “Dental Hypoplasia”[all] OR “Opacities”[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 Dentition”[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 .

The Critical Appraisal Checklist described by the Joanna Briggs Institute 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] . The same two reviewers conducted the quality assessment, and disagreements 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% Confidence Intervals (95%CI) were recorded. The original authors were contacted when further clarifications regarding the study methodology 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 . 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 I ² >50%), the random-effect model was preferred . 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 . 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.

Flowchart of selection process.

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 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 – Qatar	No	0
Corrêa-Faria et al., 2015 – Brazil	Yes	+
Yadav et al., 2015 – India	No	+
Ghanim et al., 2013 – Iraq	No	+
Basha and Swamy, 2012 – India	Yes	+
Masumo et al., 2013 – Uganda, Tanzania	Yes	+ Uganda/0 Tanzania
Targino et al., 2011 – Brazil	No	+
Zhou et al., 2011 – China	No	0
Elfrink et al., 2010 – Netherlands	No	+
Farsi, 2010 – Saudi Arabia	No	+
Hong et al., 2009 – USA	Yes	+
Hoffmann et al., 2007 – Brazil	No	+
Oliveira et al, 2006 – Brazil	Yes	+
Casanova-Rosado et al., 2005 – Mexico	Yes	+
Segovia-Villanueva et al., 2005 – Mexico	No	+
Li et al., 1996 – China	No	+
Kanchanakamol et al., 1996 – Thailand	No	+
Pascoe et al., 1994 – Australia	No	+

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