Caries-preventive effect of glass ionomer and resin-based fissure sealants on permanent teeth: An update of systematic review evidence.

CORRESPONDENCE Open Access
Caries-preventive effect of glass ionomer and
resin-based fissure sealants on permanent teeth:
An update of systematic review evidence
Steffen Mickenautsch*, Veerasamy Yengopal
Abstract
Background: This article constitutes a partial update of the original systematic review evidence by Yengopal et al.
from 15 January 2008 (published in the Journal of Oral Science in 2009) with primary focus on research quality in
regard to bias risk in trials. Its aim is to update the existing systematic review evidence from the English literature
as to whether caries occurrence on pits and fissures of teeth sealed with either GIC or resin is the same.
Methods: In addition to the 12 trials included during the original systematic review, 5 new trials were identified
during the database search (up to 26 August 2010) and 2 further trials were included from a hand search and
reference check. Of these, 3 trials were excluded and 16 were accepted for data extraction and quality assessment.
The quality of accepted trials was assessed, using updated quality criteria, and the risk of bias was investigated in
more depth than previously reported. In addition, the focus of quantitative synthesis was shifted to single datasets
that were extracted from the accepted trials.
Results: Twenty-six dichotomous and 4 continuous datasets were extracted. Meta-analysis and cumulative meta-
analysis were used in combining clinically homogenous datasets. The overall outcome of the computed datasets
suggest no difference between the caries-preventive effects of GIC- and resin-based fissure sealants.
Conclusions: This overall outcome is in agreement with the conclusions of the original systematic review.
Although the findings of the trials identified in this update may be considered to be less affected by attrition- and
publication bias, their risk of selection- and detection-/performance bias is high. Thus, verification of the currently
available results requires further high quality randomised control trials.
Introduction
Pits and fissures of posterior teeth are considered to be
highly susceptible to the adhesion of micro-organisms
and consequently, to caries. Therefore, a significant
amount of tooth decay occurs at these sites. Fissure
sealants are used to prevent occlusal caries, 71% per-
cent of occlusal decay being preventable after a once-
off fissure sealant application [1]. Evidence regarding
the efficacy and cost-effectiveness of sealants in redu-
cing occlusal caries in molars has been highlighted
[1-5]. The most commonly used sealant material is
resin composite [6-8]. Its caries-preventive effect relies
on the sealing of pits and fissures through micro-
retention, created through tags after enamel acid etch-
ing. However, these are easily destroyed by saliva con-
tamination, which reduces micro-retention and,
consequently, the caries-preventive effect [9]. Under
the generally wet conditions in the oral cavity, Glass
Ionomer Cement (GIC) offers an alternative. Owing to
its hydrophilic properties, GIC is not as moisture-sen-
sitive as hydrophobic resin [10].
In a previous systematic review Yengopal et al. [11]
conducted a meta-analysis in order to quantitatively
appraise, for the first time, the evidence regarding the
caries-preventive effect of GIC in comparison to that of
resin-based fissure sealants. This systematic review with
meta-analysis found no evidence that either material
was superior to the other in the prevention of dental
caries. Therefore, both appeared to be equally suitable
for clinical application as fissure sealant materials. These
* Correspondence: neem@global.co.za
Division of Public Oral Health, Faculty of Health Sciences, University of the
Witwatersrand - 7 York Rd., Parktown/Johannesburg 2193, South Africa
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© 2011 Mickenautsch et al; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly cited.

results were based on a systematic search of literature
up to 15 January 2008 [11]. It has been suggested that
once the search date of a systematic review is older than
even 1 year, users should check for more recent trials
on the same topic to see whether new evidence has
altered the findings of a given systematic review [12]. In
addition, the original quality assessment criteria [11]
may be questioned on grounds of being ineffective in
judging the true internal validity of trials on basis of risk
of bias [13,14]. Therefore, the aim of this update is to
provide a more in-depth assessment of bias-risk in trials.
As the inclusion of non-English language trials in the
original systematic review did not decisively influence
the overall review results [11] the focus of the in-depth
assessment and discussion of bias-risk is limited to Eng-
lish language trials, only.
Thus, the purpose of this article is to update the exist-
ing evidence from trials published in English language
regarding the review question as to whether caries
occurrence on pits and fissures of teeth sealed with
either GIC or resin is the same.
Materials and methods
In order to update the existing evidence, the systematic
literature search of the English literature was extended
beyond the original search date and a further hand
search and reference check were done. The quality of
accepted trials was assessed, using updated quality cri-
teria (Table 1) [13-16] and the risk of bias was investi-
gated in more depth than previously reported. In
addition, the focus of quantitative synthesis was shifted
to single datasets (DS) that were extracted from the
accepted trials.
Literature search, review and quality assessment of trials
The search strategy used in the previous review for Eng-
lish language articles [11] was replicated for this review
update using the search terms: “(GIC sealant* OR Glass
ionomer cement sealant) AND (caries OR tooth decay)”.
Only the start and cut-off dates were changed. The Eng-
lish databases, Biomed Central, Cochrane Oral Health
Reviews, Cochrane Library, Directory Of Open Access
Journals, Expanded Academic ASAP PLUS, Meta Regis-
ter Of Controlled Trials, PubMed and Science-Direct,
were searched for relevant papers published between 15
January 2008 (the search cut-off date of the original sys-
tematic review) and 26 August 2010. Criteria for trial
inclusion were:
- 2-or multiple arm clinical prospective study
designs;
- Comparison of GIC versus Resin fissure sealants;
- Publication in English.
Included trials were excluded after further review if:
- No outcome measure related to caries was
reported;
- No computable data, dichotomous or continuous,
per treatment group was reported;
- Resin-modified GIC (RMGIC) was used instead of
conventional, chemically cured GIC.
Included trials that passed the exclusion criteria test
were accepted for further quality assessment and data
extraction. Reviewing, data extraction and quality assess-
ment of the accepted trials was undertaken indepen-
dently by two reviewers (SM and VY). Differences were
resolved through discussion and consensus.
Unlike in the original published systematic review [11],
quality assessment of accepted trials was undertaken on
the basis of availability of evidence indicating successful
prevention of selection- and detection/performance bias
from the start to end of each trial. The new criteria
(Table 1) differed from those previously used in the first
review [11]. It has been argued that the inclusion of bias-
preventing measures (e.g. randomisation, blinding/mask-
ing) into the trial methodology only demonstrates an
attempt to reduce bias risk but does not carry proof in
itself that such attempt was indeed successful and that it
is far more important to judge trial quality according to
evidence that indicates to what extent such attempt has
succeeded [13]. Against this background the quality cri-
teria were adjusted accordingly. For example; if a trial
merely reported that randomisation was conducted;
reported only the name of the randomisation method
used or included a detailed description of the randomisa-
tion process without providing any evidence that rando-
misation was indeed effective throughout the trial; then
this was regarded as inadequate.
Potential attrition- and publication bias was not investi-
gated in the original meta-analysis [11]. In this update,
sensitivity analysis was done, using the RevMan Version
4.2 statistical software of The Nordic Cochrane Centre,
The Cochrane Collaboration (Copenhagen; 2003), in order
to investigate potential attrition bias risk in trials. To
investigate publication bias a funnel plot was generated,
using the datasets from the included clinical trials. The
standard error (SE) of the mean differences was plotted on
the Y-axis, and the log of the Relative Risk (RR) on the
X-axis, using MIX Version 1.7 meta-analysis software [17].
In addition, Egger’s linear regression method [18] was
used to calculate an intercept with a 95% Confidence
Interval (CI), with statistical significance set at a = 0.05.
We anticipated that many of the identified trials would
be of split-mouth design. The split-mouth study design is
commonly used in dentistry to test interventions and has
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Table 1 Quality assessment criteria of trials
Selection bias
Score Criteria Impact on bias risk
Randomisation and concealment
A (i) Randomisation: Details of any adequate type of allocation
method that generates random sequences with the patient as
unit of randomisation are reported.1
Doubts may still exist whether the trial results are influenced by
selection bias but no indication can be found from the trial report to
support such doubt.
(ii) Concealment: Trial provides evidence2 that concealment was
indeed effective and that the random sequence could not have
been observed or predicted throughout the duration of the trial.
B (i) Randomisation: Details of any adequate type of allocation
method that generates random sequences with the patient as
unit of randomisation are reported.1
Despite the implementation of method considered to be able to
prevent unmasking of the concealed allocation sequence through
direct observation and prediction, there are reasons to expect that
the concealed allocation sequence may have been unmasked during
the cause of the trial.
(ii) Concealment: Trial reports on any adequate method to
prevent direct observation3 and prediction4 of the allocation
sequence and sequence generation rules.
C (i) Randomisation: Details of any adequate type of allocation
method that generates random sequences with the patient as
unit of randomisation are reported.1
Despite the implementation of method considered to be able to
prevent unmasking of the concealed allocation sequence through
direct observation, there are reasons to expect that operators could
have predicted the concealed allocation sequence.
(ii) Concealment: Trial reports on any adequate method to
prevent direct operator observation of allocation sequence and
sequence generation rules3. However, the allocation sequence
and sequence generation may have been sufficiently predicted.
D (i) Randomisation: Details of any adequate type of allocation
method that generates random sequences with the patient as
unit of randomisation are reported.1
Despite the theoretical chance for each patient to be allocated to
either treatment group, operator knowledge of the allocation
sequence may have lead to patient allocation that favoured the
outcome of one type of treatment above the other.
(ii) Concealment: The trial report does not include information
on how the allocation of random sequence was concealed. The
allocation could have been directly observed and/or predicted.
0 Trial does not comply with criteria A - D. No guaranty of equal chance for patients to be allocated to either
treatment group, thus allocation may have favoured the outcome of
one type of treatment above the other.
Baseline data for randomised trials
A Baseline data collected before randomisation and reported for both
treatment groups. Data shows no significant differences between
both groups.
Evidence is given that randomisation has lead to equal groups
suggesting little risk of selection bias.
B Baseline data collected before randomisation and reported for both
treatment groups. Data shows significant differences between both
groups but has been statistically adjusted appropriately.
Differences have been adjusted, thus the influence of possible
selection bias appears to be reduced.
C Baseline data collected before randomisation and reported for both
treatment groups. Data shows significant differences between both
groups without being statistically adjusted.
Reported differences may be due to ineffective randomisation, thus
indicate risk of selection bias.
0 Trial does not comply with criteria A - C. No evidence is given whether randomisation has indeed lead to
equal groups with differences beyond chance, thus differences may
exists indicating selection bias.
Detection/Performance bias
Blinding/Masking
Score Criteria Impact on bias risk
A (i) Trial reports on any type of method that is known to prevent
patient AND operator AND evaluator to discern whether patients
are allocated to the test- or the control group (Blinding/
Masking).
Evidence is given that the trial results may not have been influenced
by detection/performance bias that may have favored the outcome
of one type of treatment above the other.
(ii) Trial reports a process with which the effect of Blinding/
Masking was evaluated, as well as the results of such evaluation.
B (i) Trial reports on any type of method that is known to prevent
patient AND operator AND evaluator to discern whether patients
are allocated to the test- or the control group (Blinding/
Masking).
Doubts may still exist whether the trial results are influenced by
detection/performance bias but no indication can be found from the
trial report to support such doubt. However, no evaluation of the
Blinding/Masking effect has been included in the trial, thus no
evidence for lack of bias is given.
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the advantage of having an individual serve as both the
experiment and control. In this study design, one or more
pairs of teeth (e.g. primary molars) form the unit of rando-
misation. Strictly, these pairs are not independent and
should be analysed as “paired data” on a patient basis.
However, similar to other systematic reviews where split-
mouth trials are included [2] we analysed the pairs of
tooth surfaces independently for differences whether they
are carious or not. The fact that this would result in
slightly narrower confidence intervals was considered in
the discussion of the overall results.
Data extraction and analysis
All data concerning primary and secondary outcomes of
accepted trials were extracted either as single dichotomous
datasets (containing the number of observed effects (n)
and the total number of evaluations (N) for both the con-
trol and the test groups) or as single continuous datasets
(containing the mean value, standard deviation and total
number of evaluations for both the control and the test
groups). For dichotomous datasets the Relative Risk (RR,
95% CI), and for continuous datasets the Mean Difference
(MD, 95% CI), was computed, using the Cochrane Rev-
Man, Version 4.2 software package. Statistical significance
was set at a = 0.05.
Meta-analysis, using RevMan Version 4.2 statistical
software by The Nordic Cochrane Centre, The
Cochrane Collaboration (Copenhagen; 2003), was con-
sidered for datasets only if they complied with criteria
for clinical homogeneity. Datasets were considered to be
Table 1 Quality assessment criteria of trials (Continued)
(ii) Trial report does not give reason for doubt that the patient
allocation to either the test- or the control group has been
unmasked throughout the duration of the trial.
C (i) Trial reports on any type of method that is known to prevent
patient AND operator AND evaluator to discern whether patients
are allocated to the test- or the control group (Blinding/
Masking).
Despite the implementation of method considered to be able to
prevent unmasking, there are reasons to expect that operators/
patients could have discovered the allocation.
(ii) Trial report gives reason for doubt that the patient allocation
to either the test- or the control group has been unmasked
throughout the duration of the trial.
0 No process reported or implemented able to blind/mask patients
AND operators whether patients where allocated to either the test-
or the control group (It is insufficient to report that blinding/masking
was done without reporting the details of the process).
Knowledge about the patient allocation may have caused patients/
operator to act in a way that may have favoured the outcome of
one type of treatment above the other,
Attrition bias
Loss - to follow up
Score Criteria Impact on bias risk
A Available case analysis, loss-to-follow up reported per treatment
group. Subsequent sensitivity analysis does not indicate a possible
risk of bias.
The trial allows extracting evidence that attrition may not have
favoured the outcome of one type of treatment above the other.
B Available case analysis, loss-to-follow up reported per treatment
group. Subsequent sensitivity analysis indicates a possible risk of bias.
The trial allows assessing the risk that attrition may have favoured
the outcome of one type of treatment above the other.
0 Trial does not report number of included participants per treatment
group at baseline or gives any indication that would allow
ascertaining the loss-to-follow up rate per treatment group.
The trial carries an unknown risk that attrition may have favoured the
outcome of one type of treatment above the other.
Run-in phase
A No run-in phase reported or discernable during which patients were
given the active treatment or the placebo/control.
The trial may not carry the risk of bias due to exclusion of patients
who would not respond well to e.g. the active treatment.
0 Run-in phase reported or discernable during which patients were
given the active treatment or the placebo/control.
During a run-in phase only patients were selected for randomisation
that have responded/not responded to the active treatment of the
placebo/control. This may favour the outcome of one type of
treatment above the other as patients who did not respond well to
either are excluded.
Trial endpoints
0 The trial reports on secondary or surrogate outcomes as endpoints. Even if the surrogate results would highly correlate with primary (i.e.
clinical) outcomes, they cannot serve as valid replacements and need
to be regarded for hypothesis development, only.
A The trial reports on primary outcomes as endpoints. Primary outcomes may provide evidence for hypothesis testing.
1Excluded are types of allocation methods that are considered as inadequate: cluster randomisation, fixed block randomisation with block size 2, minimization,
alternation, randomisation of teeth, use of date of birth or patient record number, “quasi"-randomisation, split-mouth.
2E.g. by reporting results of the Berger-Exner Test or any other statistical tests that show that covariates of compared groups were similar at baseline.
3E.g. by opening of opaque envelope, obtaining allocation from tables, computer generated or from other sources.
4E.g. central randomisation, sequence allocation by other than operator; excluding varied block randomisation.
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clinically homogeneous if they covered the same type of
dentition; type of teeth; study length; type of evaluation
method; type of GIC (high- or low viscosity) and stated
whether the resin-based fissure sealant material con-
tained fluoride. The percentage of total variations across
datasets (I2) was used in assessing statistical heterogene-
ity [19]. Statistical significance for assessing statistical
heterogeneity was set at a = 0.10. A fixed effects model
was used for meta-analysis under condition of statistical
homogeneity of datasets (p > 0.10) and a random-effects
model was used for the others. Pooled datasets were
assigned a Mantel-Haenszel weight directly proportion-
ate to the sample size.
Cumulative meta-analysis, using MIX Version 1.7
meta-analysis software [17], was performed on datasets
of consecutive follow-up periods, in order to investi-
gate whether a trend of the available evidence might
be observed in line with increasing time after sealant
application. Care was taken to select only clinically
homogenous datasets. A random-effects model was
used under condition of statistical heterogeneity of
datasets (p < 0.10).
Results
Literature search
In addition to the 12 trials included during the original
systematic review [20-31], five trials [32-36] were identi-
fied during the new database search. A further two trials
[37,38] from the hand search and reference check were
included (Figure 1). Of these 19 trials, 3 were excluded
[34-36], owing to lack of reported caries outcome [35]
and reporting on RMGIC as a test material [34,36]. Six-
teen trials passed the exclusion criteria and were
accepted for data extraction and quality assessment
[20-33,37,38].
Dataset extraction and analysis
Twenty-six dichotomous (DS 01-12,15-28,30) and 4
continuous datasets (DS 13,14,23,29) were extracted
from the 16 accepted trials. Characteristics of these
trials and their datasets are shown in Table 2. The arti-
cles by Forss et al. [37] and Forss and Halme [28]
reported each of different datasets from the same trial.
Three of the accepted 16 trials followed a parallel group
design [25,26,33], while all other trials were split-mouth
studies.
Sixteen of the 30 datasets showed no difference
between the two materials after periods lasting from 6
months to 7 years (Tables 2 and 3). Twelve dichotomous
(DS 05, 10,11,17-21,27,30) and two continuous datasets
(DS 13,14) showed statistically significant (p < 0.05) dif-
ferent results. Of these, seven dichotomous datasets (DS
06,10-12,20,21,27) extracted from five trials [22-24,27,31]
were in favour of resin-based fissure sealants after 2 to 3
years. Five dichotomous datasets (DS 05,17-19,30)
extracted from three trials [21,26,38] were in favour of
GIC-based fissure sealants after 3 to 5 years. Two contin-
uous datasets (DS 13,14) from one trial [25] reporting on
secondary outcomes, such as the DFS and DMFS incre-
ment, were also in favour of resin-based fissure sealants
after 2 years.
Three of the datasets with statistically significant
results (DS 17-19) were derived from one trial including
high-viscosity GIC [26].
Meta-analysis
Of the 30 datasets, two groups of datasets, DS 04,21,27
after 3 years and DS 05,07 after 4 years, were considered
to have each met the criteria for clinical homogeneity
and were combined in two meta-analyses. The results
were generated in the form of two forest plots (Figure 2
and 3). These datasets included first permanent molars
sealed either with low-viscosity GIC or with resin mate-
rial lacking fluoride and were evaluated by visual, clini-
cal examination.
Figure 2 shows a pooled relative risk of 2.62 (95% CI:
1.71 - 4.00; p < 0.00001), suggesting a 2-3 times higher
chance of caries for teeth sealed with low-viscosity GIC
than for those filled with resin, after 3 years. Additional
analysis established a low risk of statistical heterogeneity
(I2 = 56.7%, p = 0.13). For that reason a fixed-effects
model was used for this meta-analysis.
Figure 3 shows a pooled relative risk of 0.53 (95% CI:
0.07 - 3.73; p = 0.52), suggesting no difference between
the chance of caries development in teeth sealed with
low-viscosity GIC or resin after 4 years. Additional ana-
lysis established a high risk of statistical heterogeneity
(I2 = 92.8%, p = 0.0002). For that reason a random-
effects model was used for this meta-analysis. The sig-
nificant statistical heterogeneity may be related to the
inconsistency in the size of the treatment effects as the
trials from which both datasets were extracted were
similar in type of materials, sample size, outcome mea-
sure, evaluation criteria and method, as well as type of
dentition, teeth, age of patients and study period (Table
2). Further investigation, by using the available trial
information, did not result in any other possible
explanation.
Cumulative meta-analysis
In order to investigate whether a possible trend may be
assumed in the comparison of GIC and resin, the chron-
ological results from 5 datasets, concerning sealed teeth
after 2 years (DS 06), 2-3 years (DS 21), 3 years (DS
04,27) and 3.64 years (DS 05) [20-22,27,31], were
included in a cumulative meta-analysis and its results
were generated in the form of a forest plot (Figure 4).
As with both meta-analyses (Figure 2 and 3), all datasets
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included first permanent molars sealed either with low-
viscosity GIC or resin material without fluoride and
were evaluated by visual, clinical examination. They
were thus considered clinically homogenous in all
aspects except their follow-up periods. However, a sta-
tistical heterogeneity was established (I2 = 89.2%; p <
0.00001) that may be attributed to the differences in the
length of follow-up periods, so a random-effects model
was used. The cumulative Relative Risk indicates no sta-
tistical significant difference between the two materials
after 5 years (RR 1.33; 95% CI: 0.39 - 4.45; p = 0.65). A
shift of the cumulative relative risks towards the value
of 1.00, as well as a shift of the cumulative 95% confi-
dence intervals below a relative risk of 1.00 from the
period after 2 to 3.64 years can be observed (Figure 4).
Quality assessment of trials and risk of bias
Selection-, Detection-/Performance bias risk
The results of the quality assessment regarding selec-
tion- and detection/performance bias are shown in
Table 4. None of the accepted trials reported sufficient
details of any randomisation process that had indeed
Figure 1 Flow diagram of trial selection. N = Number of trials; DS = Dataset number.
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Table 2 Details of accepted trials
Article DS Study
design
GIC treatment group Resin treatment group Outcome
measure
Evaluation Dentition/
Teeth/
Restoration
Study
period
Type of
material
BSL N n LTF Type of
material
BSL N n LTF Criteria Method
Dichotomous datasets
Oba et al.,
2009 [32]
01 SM Ketac Molar 91 56 6 35 Fissurit F 116 81 8 35 Caries Caries present Visual First
permanent
molars
3 years
Barja-
Fidalgo
et al., 2009
[33]
02 PG Fuji IX 46 46 1 0 Delton 46 46 2 0 Caries Cavity that had
clearly penetrated
the dentin or if a
radiolucency in
dentin could be
seen on the
bitewing X- ray
Visual
and X-
Ray
First
permanent
molars
6
months
03 46 21 2 25 46 28 7 18 5 years
Karlzén-
Reuterving
and van
Dijken, 1995
[20]
04 SM Fuji III 74 72 1 2 Delton 74 72 3 2 Caries Caries present Visual First
permanent
molars
3 years
Arrow and
Riordan,
1995 [21]
05 SM Ketac Fil 465 412 6 53 Delton 465 412 31 53 Caries When a cavity was
present
Visual First
permanent
molars
Mean
3.64
(SD
0.11)
years
Williams
et al., 1996
[22]
06 SM Fuji III 430 295 19 135 Delton 430 295 4 135 Caries Caries present Visual First
permanent
molars
2 years
07 430 222 22 208 430 222 16 208 4 years
Rock et al.,
1996 [23]
08 SM Baseline 172 160 3 12 Fluoro-
Shield
172 162 0 10 Caries Caries present Visual First
permanent
molars
6
months
09 172 157 6 15 172 158 1 14 1 year
10 172 130 14 42 172 132 2 40 2 years
11 172 124 18 48 172 129 3 43 3 years
Kerrvanto-
Seppälä
et al., 2008
[24]
12 SM Fuji III 1025 657 27 368 Delton 1025 657 7 368 Caries If dentine caries
was detected
Visual 2nd
permanent
molars
3 years
Beiruti et al.,
2006
15 PG Fuji IX 180 180 0 0 Visio
Seal
180 180 1 0 Caries Caries present Visual First
permanent
molars
1 year
[26] 16 180 154 0 26 180 161 6 19 2 years
17 180 154 3 26 180 138 13 42 3 years
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Table 2 Details of accepted trials (Continued)
18 180 143 7 37 180 123 21 57 4 years
19 180 80 8 100 180 76 27 104 5 years
Poulsen
et al., 2006
[27]
20 SM Fuji III 364 364 34 0 Delton 364 364 10 0 Radiograp-
hically
carious
Lesions into
dentine
X-Ray First
permanent
molars
2.3 -
3.2
years
21 364 364 23 0 364 364 10 0 Clinically
carious
Danish municipal
dental service
criteria
Visual
Forss and
Halme,
19981 [28]
22 SM Fuji III 166 97 23 69 Delton 166 97 16 69 Caries Caries lesion
present/Arrested
caries present
Visual Permanent
molars/
premolars
7 years
Mejàre and
Mjör, 1990
[29]
24 SM Fuji III 44 36 0 8 Delton 117 75 6 42 Caries Caries present Visual Permanent
molars/
premolars
5 years
25 44 36 0 8 Concise 47 18 2 29
Boksmann
et al., 1987
[30]
26 SM Fuji III 125 116 0 9 Concise 122 115 0 7 Caries Caries present Visual Permanent
molars
6
months
Poulsen
et al., 2001
[31]
27 SM Fuji III 170 116 44 54 Delton 170 116 13 54 Caries White, yellow,
brown
discoloration of
the fissure or cavity
Visual First
permanent
molars
3 years
Forss et al.,
19941 [37]
28 SM Fuji III 166 151 7 15 Delton 166 151 7 15 Caries Caries lesion
present/Arrested
caries present
Visual Permanent
molars/
premolars
2 years
Williams
and Winter,
1981 [38]
30 SM ASPA No info 4862 642 No
info
Concise No
info
4862 932 No
info
Caries Caries present Visual First
permanent
molars
3.84
years
Article DS Continuous datasets
Patient
character-
istics/
potential
confounders*
Type of
material
N x SD LTF Type of
material
N x SD LTF Outcome
measure
Criteria Method Dentition/
Teeth/
Restoration
Study
period
Songpaisan
et al., 1995
[25]
13 PG Fuji III 128 0.48 1.03 14% Delton 133 0.05 0.57 14% DFS
increment
DFS Visual Permanent
molars
2 years
14 128 1.82 2.60 133 0.98 1.72 DMFS
increment
DMFS
Forss and
Halme,
19981 [28]
23 SM Fuji III 97 0.13 0.40 69 Delton 97 0.13 0.37 69 Caries
increment
on
approximal
tooth
surfaces
adjacent to
materials
Caries lesion
present/Arrested
caries present
Visual Permanent
molars/
premolars
7 years
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Table 2 Details of accepted trials (Continued)
Forss et al.,
19941 [37]
29 SM Fuji III 151 0.09 0.34 15 Delton 151 0.13 0.41 15 2 years
Article Place of trial Age of
patients
Patient
characteristics/
inclusion/
exclusion
criteria
Fluoride
exposure
from
other
sources
Oba et al.,
2009 [32]
Study conducted
in a boarding
school in the city
of Kırıkkale/Turkey
7-11 years Children received instructions on good oral health care and were individually shown how to clean their teeth prior to the
start of the treatment; inclusion criteria were: (1) sound pits and fissures in fully erupted first molars; and (2) pits and fissures
diagnosed with an early enamel lesion; exclusion criteria were: (1) partly erupted first molar; (2) an obvious cavity in the
occlusal surface; and (3) the presence of a restoration or a sealant (or part of it) in the pit and fissure system;
Resin-based fissure
sealant material
containing fluoride
Barja-
Fidalgo et
al., 2009
[33]
Study carried out
in the Department
of Paediatric
Dentistry, Rio de
Janeiro State
University, Rio de
Janeiro/Brazil;
mean age
6.8 years
(±0.98 SD)
With at least 1 permanent first molar erupted and 2 or more primary molars decayed, filled, or extracted due to caries; most
from low socio-economic background with high caries-risk; the participants were also given oral hygiene instructions and
dietary counselling; those who had dental care needs were referred to the paediatric dental clinic for appropriate restorative
and surgical treatment; participants reported brushing their teeth daily, 11% reported using dental floss regularly, and 67%
had a dental check-up once a year first molars that presented a sound occlusal surface or occlusal caries at the D1 level
(non-cavitated enamel lesion) entered the study; low patient compliance and high saliva contamination during treatment
reported.
-
Karlzén-
Reuterving
and van
Dijken, 1995
[20]
Children from
Umea/Sweden
mean age
7 years,
1 month
Teeth without clinical evidence of caries were sealed -
Arrow and
Riordan,
1995 [21]
Children from
Perth/Australia
mean age 7
(SD 0.72)
years
With sound, unsealed, homologous 1st permanent molars -
Williams
et al., 1996
[22]
Children from
Suffolk/UK
6-8 years Recently erupted visually caries free 1st permanent molars; resealed teeth were excluded Fluoride
concentration of
drinking water 0.1 -
0.5 mgF/l
Rock et al.,
1996 [23]
Children from
Tamworth,
Staffordshire/UK
7-8 years Caries free fully erupted 1st permanent molars; children had evidence of caries in primary teeth The resin-based
sealant FluroShield
contains fluoride;
fluoride
concentration of
drinking water 0.13
ppm
Kerrvanto-
Seppälä
et al., 2008
[24]
Children from
Varkaus/Finland
12-16 years 2nd permanent molars considered to be at risk of caries were sealed; teeth with lost resin sealant were resealed and not
excluded from the study.
-
Beiruti et al.,
2006 [26]
Children from
Damascus/Syria
mean age
7.8 years
No cavities in primary teeth; inclusion criteria: sound pits and fissures in fully erupted 1st permanent molars, pits and
fissures with early enamel lesion and/or small dentinal lesion; exclusion criteria: partly erupted tooth, obvious occlusal cavity,
presence of restoration or sealant in pits and fissures.
-
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Table 2 Details of accepted trials (Continued)
Poulsen
et al., 2006
[27]
Children from
Vaerlose/Denmark
8-13 years Mean DMFS was between 0.5 and 0.7 for 12-year-old children and between 1.4 and 1.8 for 13-year-old children; sound
surfaces, and surfaces with initial or arrested caries (white or brown fissures) were sealed, if the dentist’s clinical assessment
indicated a caries risk; only children with both clinical and radiographic data were included in the present study
Fluoride content of
the drinking water
0.25 ppm; all children
commonly use
fluoridated
toothpaste
Forss and
Halme,
2006 [28]
Children from
Raisio/Finland
5-14 years Contra-lateral pair of newly erupted non-sealed permanent molars or premolars -
Mejàre and
Mjör, 1990
[29]
- mean age
9.2 (5.7 -
15.0) years
- -
Boksmann
et al., 1987
[30]
- 6-18 years Patients had not received topical fluoride treatment for at least 3 months prior. Fluoride content of
the drinking water 1
ppm or more
Poulsen et
al., 2001
[31]
Children from
Damascus/Syria
7 years Only children with at least one pair of caries free permanent 1st molars or with incipient lesions; average DMFT 0.6 -0.7. -
Forss et al.,
1994 [37]
Children from
Raisio/Finland
5-14 years Contra-lateral pair of newly erupted non-sealed permanent molars or premolars -
Williams
and Winter,
1981 [38]
- 6-8 and 11-
13 years
- -
Songpaisan
et al., 1995
[25]
Children from
Bangkok/Thailand
12-13 years From very low to medium socio-economic background; children with at least 3 sound permanent molars (erupted
sufficiently)
Included in a fluoride
mouth rinse
programme (0.2%
NaF) every 2 weeks;
fluoride
concentration of
drinking water 0.1 -
0.2 ppm
DS = Dataset number; BSL = Number of teeth at baseline; N = Number of teeth evaluated; n = Number of teeth with caries, LTF = Loss-to-follow-up; x = Mean; SD = Standard deviation; PG = Parallel group design;
SM = Split-mouth design.
1Different datasets reported from same trial.
2Number of pits reported, instead of the number of sealed teeth.
* Potential confounders = Reported fluoride exposure; high-sugary diet; poor oral hygiene; high past caries experience.
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given each patient the same chance to be allocated to
either the GIC or the resin group and to ensure that
direct observation and prediction of the allocation
sequences was successfully prevented. Only three trials
[25,26,33] had reported baseline data collected before
randomisation and reported for both treatment
groups, statistically compared this data between
groups and found the difference statistically not signif-
icant (p > 0.05). No accepted trial reported on suc-
cessful blinding/masking of patients, operators and
trial evaluators.
Attrition bias risk
Sensitivity analysis was used in computing all datasets,
under the assumption that either:
(i) All pits and fissures of sealed teeth lost to follow-
up developed caries;
(ii) None of the sealed teeth lost to follow-up devel-
oped caries.
The results of either situation did not change the
conclusions for the majority of the datasets. However,
Table 3 Results of individual datasets
Article DS Dichotomous datasets
RR 95% CI p-value
Oba et al., 2009 [32] 01 1.08 0.40 - 2.96 0.87
Barja-Fidalgo et al., 2009 [33] 02 0.50 0.05 - 5.32 0.57
03 0.38 0.09 - 1.65 0.20
Karlzén-Reuterving and van Dijken, 1995 [20] 04 0.33 0.04 - 3.13 0.34
Arrow and Riordan, 1995 [21] 05 0.19 0.08 - 0.46 0.0002*
Williams et al., 1996 [22] 06 4.75 1.64 - 13.79 0.004**
07 1.38 0.74 - 2.55 0.31
Rock et al., 1996 [23] 08 7.09 0.37 - 136.11 0.19
09 6.04 0.74 - 49.58 0.09
10 7.11 1.65 - 30.66 0.009**
11 6.24 1.89 - 20.66 0.003**
Kerrvanto- Seppälä et al., 2008 [24] 12 3.86 1.69 - 8.79 0.001**
Beiruti et al., 2006 [26] 15 0.33 0.01 - 8.13 0.50
16 0.08 0.00 - 1.42 0.08
17 0.21 0.06 - 0.71 0.01*
18 0.29 0.13 - 0.65 0.003*
19 0.28 0.14 - 0.58 0.0006*
Poulsen et al., 2006 [27] 20 3.40 1.71 - 6.78 0.0005**
21 2.30 1.11 - 4.76 0.02**
Forss and Halme, 19981 [28] 22 1.44 0.81 - 2.55 0.21
Mejàre and Mjör, 1990 [29] 24 0.16 0.01 - 2.73 0.20
25 0.10 0.01 - 2.03 0.14
Boksmann et al., 1987 [30] 26 Not estimable
Poulsen et al., 2001 [31] 27 3.38 1.93 - 5.94 <0.0001**
Forss et al., 19941 [37] 28 Not estimable
Williams and Winter, 1981 [38] 30 0.69 0.51 - 0.92 0.01*
Article DS Continuous datasets
MD 95% CI p-value
Songpaisan et al., 1995 [25] 13 0.43 0.23, 0.63 <0.0001**
14 0.84 0.30, 1.38 0.002**
Forss and Halme, 19981 [28] 23 0.00 -0.11, 0.11 1.00
Forss et al., 19941 [37] 29 -0.04 -0.12, 0.04 0.36
DS = Dataset number; RR = Relative risk; MD = Mean difference; CI = Confidence interval; Not estimable = data from both treatment groups are essentially the
same: p = 1.00.
*Statistically significant difference, in favour of GIC.
**Statistically significant difference, in favour of Resin.
1 Different datasets reported from same trial.
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a possible risk of attrition bias was identified for the
results of four datasets (DS 06,12,24,25) extracted from
three trials [22,24,29]. Under the assumption that all
pits and fissures of sealed teeth lost to follow-up devel-
oped caries, the results of two datasets (DS 06,12)
would not be statistically significantly in favour of
resin: DS 06 - RR 1.11 (95% CI: 0.92 - 1.33; p = 0.28);
DS 12 - RR 1.05 (95% CI: 0.94 - 1.18; p = 0.36) and
the results of two datasets (DS 24,25) would be statisti-
cally significantly in favour of GIC: DS 24 - RR 0.44
(95% CI: 0.23 - 0.86; p = 0.02); DS 25 - RR 0.28 (95%
CI: 0.14 - 0.53; p = 0.0001).
In line with the potential influence of attrition bias on
datasets, the meta-analysis results (Figure 2 and 3) were
not affected.
Under the assumption that all pits and fissures of
sealed teeth lost to follow-up developed caries, the
results of the cumulative meta-analysis (Figure 4) would
only change towards a further shift of the cumulative
relative risks towards the value of 1.00, and in a narrow-
ing of the cumulative 95% confidence interval after 3.64
years (RR 1.14 - 95% CI: 0.081 - 1.60; p = 0.46).
In addition to the risk of bias due to loss-to-follow up,
no trial indicated that a run-in phase was implemented
before randomisation (Table 4).
Publication bias risk
Publication bias was investigated, using one funnel plot
(Figure 5). The funnel plot concerning data for caries
progression showed an even distribution that did not
suggest publication bias. Egger’s linear regression
method for the same datasets showed an intercept of
0.05 (95% CI: -1.74, 1.85; p = 0.95). The regression
result was not statistically significant.
Unlike the original systematic review, non-English lan-
guage articles were not included in this partial update
and this needs to be addressed in a future update,
including not only those in Portuguese and Spanish but
in other languages too.
Discussion
The aim of this article was to update the existing evi-
dence from trials published in English language regard-
ing the review question as to whether caries occurrence
on pits and fissures of teeth sealed with either GIC or
Figure 2 Forrest plot of meta-analysis results concerning caries on sealed first permanent molars after 3 years. Study or sub-category =
Dataset number; GIC = Glass-ionomer cement; RR = Relative Risk; CI = Confidence Interval; n = Number of teeth with caries; N = Total number
of evaluated teeth.
Figure 3 Forrest plot of meta-analysis results concerning caries on sealed first permanent molars after 4 years. Study or sub-category =
Dataset number; GIC = Glass-ionomer cement; RR = Relative Risk; CI = Confidence Interval; n = Number of teeth with caries; N = Total number
of evaluated teeth.
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resin is the same. The article constitutes a partial update
of the original systematic review evidence with primary
focus on research quality in regard to bias risk in trials.
During the new systematic literature search seven
more trials [32-38] could be included for review. The
reason for this was that five new trials had been pub-
lished since the cut-off date of the original search; a
more thorough hand search and reference check of the
literature had been done, and broader inclusion criteria
were used. Of the seven new included trials, three were
excluded [34-36] as they did not comply with the stated
exclusion criteria.
In comparison to the original published systematic
review [11], this update presents an improvement in the
output of its systematic search of English trials.
However, other aspects in the methodology of this
review update might still have contributed to limitations
in its results: (i) not all relevant publications were listed
in the selected databases; (ii) The chosen search terms
may not have been broad enough; (iii) not all relevant
publications could be found through a hand search and
reference check. In addition and as this update is limited
to English language trials, only, a future update of the
non-English evidence of the original systematic review is
required. Although, the inclusion of non-English lan-
guage trials in the original systematic review did not
decisively influence the overall review results [11] an
update of the non-English evidence of the original sys-
tematic review would confirm (i) whether the new find-
ings from non-English trials substantially differ from the
Figure 4 Forrest plot of cumulative meta-analysis results concerning caries on sealed first permanent molars. RR = Relative Risk.
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English language trials and (ii) whether results from any
new non-English language trials would influence the
overall review results.
Selection-, Detection-/Performance bias risk
Of the accepted 16 trials, only 3 trials followed a parallel
group design [25,26,33] and all other were split-mouth
studies. Mejáre et al. have cautioned against the split-
mouth design as “randomised”, as the common practice
of including subjects with at least one pair of caries-free
molars results in exclusion of caries-active subjects [39].
An obvious selection bias is thus created, as not all sub-
jects will have the same chance to participate. Mejáre et
al. have rightfully suggested that the split-mouth trial
design should therefore be regarded as “quasi-
randomised”. Thus, reviews where inclusion criteria
include only randomised-control trials should, in theory,
exclude trials that use the split-mouth study design. Fol-
lowing the example of other systematic reviews [2], the
data from split-mouth trials was analysed as indepen-
dent data. This will have caused narrower confidence
intervals and thus may have favoured the reported out-
comes of one type of treatment above the other. How-
ever, the so caused differences in confidence intervals
may be considered to only be slight [2] and its correc-
tion would not have affected the general impact of
selection bias on the relative risk (RR, 95% CI) per data-
set (Table 3) due to lack of adequate randomisation
[39-41]. In addition, wider confidence intervals would
have provided only stronger indication of no difference
Table 4 Results of quality assessment of accepted trials
Article DS Selection bias Detection/Performance
bias
Attrition bias Trial
outcome
Randomization Baseline
data
Blinding/Masking Loss-to-follow
up
Run-in
phase
Oba et al., 2009 [32] 01 0 0 0 A A A
Barja-Fidalgo et al., 2009 [33] 02 0 A 0 A A A
03 0 A 0 A A A
Karlzén-Reuterving and van Dijken,
1995 [20]
04 0 0 0 A A A
Arrow and Riordan, 1995 [21] 05 0 0 0 A A A
Williams et al., 1996 [22] 06 0 0 0 B A A
07 0 0 0 A A A
Rock et al., 1996 [23] 08 0 0 0 A A A
09 0 0 0 A A A
10 0 0 0 B A A
11 0 0 0 A A A
Kerrvanto-Seppälä et al., 2008 [24] 12 0 0 0 B A A
Beiruti et al., 2006 [26] 15 0 A 0 A A A
16 0 A 0 A A A
17 0 A 0 B A A
18 0 A 0 B A A
19 0 A 0 A A A
Poulsen et al., 2006 [27] 20 0 0 0 A A A
21 0 0 0 A A A
Forss and Halme, 19981 [28] 22 0 0 0 A A A
Mejàre and Mjör, 1990 [29] 24 0 0 0 B A A
25 0 0 0 B A A
Boksmann et al., 1987 [30] 26 0 0 0 A A A
Poulsen et al., 2001 [31] 27 0 0 0 A A A
Forss et al., 19941 [37] 28 0 0 0 A A A
Williams and Winter, 1981 [38] 30 0 0 0 0 A A
Songpaisan et al., 1995 [25] 13 0 A 0 n.e. A 0
14 0 A 0 n.e. A 0
Forss and Halme, 19981 [28] 23 0 0 0 n.e. A 0
Forss et al., 19941 [37] 29 0 0 0 n.e. A 0
DS = Dataset number, n.e. = Not evaluated.
1 Different datasets reported from same trial.
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between both types of treatment and would not have
changed the overall conclusion from the current analysis
results.
All of the accepted trials appear to be limited by risk
of selection- and detection-/performance bias. Bias or
systematic error may affect studies, causing either an
over- or under-estimation of the treatment effect of an
investigated clinical procedure. Overestimation has been
observed to be the most common [40]. Kjaergard et al.
reported a treatment effect overestimation of 48%
caused by lack of random sequence allocation [41] and
Egger et al. reported a treatment effect overestimation
of 54% and 53% due to lack of allocation concealment
and lack of evaluator blinding, respectively [42].
It has been emphasized that selection bias can only be
successfully prevented if the allocation sequence remains
truly random and free from potential interference
throughout the trial [13,14]. Thus, it is important that
trials should include an effective process for concealing
the random allocation sequence and that by the end of
each trial this process has indeed prevented direct obser-
vation and prediction of the random sequence allocation
[13,14]. Quality assessment in terms of the internal valid-
ity of trials should therefore be a measure of the result of
random sequence allocation and allocation concealment,
and not only of its reported attempt. All trials accepted
in this systematic review failed to report not only on evi-
dence of successful sequence allocation and allocation
concealment results, but also on necessary details about
how sequence allocation and allocation concealment
were attempted (Table 4). None of the trials, therefore,
provide any guarantee that each patient had an equal
chance of being allocated to either treatment group and
thus, their allocation may have favoured the outcome of
one type of treatment above the other. One measure for
testing whether random sequence allocation has not been
successful is testing whether covariates differ between
treatment groups at baseline [13]. Only three articles had
included such a test and reported on its outcome
[25,26,33]. The statistically non-significant results (p >
0.05) suggest a successful random allocation (Table 4).
However, doubt remains regarding potential bias risk, as
other non-balanced covariates may exist, that were not
tested for and/or not reported.
From the onset, in all trials successful blinding or
masking appeared not to have been possible, owing to
the obvious differences in clinical appearance between
GIC and resin sealants. For that reason the allocation to
either treatment group was visible to patients, operators
and evaluators. However, the difficulties of successful
blinding still carry the danger of detection-/performance
bias, which may thus have affected the trials’ results.
Potential knowledge of superiority claims prior to the
trial may have led patients to change their oral hygiene
habits, operators to place restorations more carefully or
evaluators to apply evaluation criteria more subjectively.
This in turn may have favoured the outcome of one
type of treatment over the other.
Attrition bias risk
Sensitivity analysis may be used in establishing whether
missing data could have affected trial outcomes by
assuming that the numbers of restoration lost to evalua-
tion were either failures or successes [43]. Comparison
of the analysis results with reported trial outcomes indi-
cates whether different conclusions should be drawn.
Sensitivity analysis was conducted for all datasets. The
analysis results differed from reported outcomes of four
datasets (DS 06,12,24,25) extracted from three trials
[22,24,29]. According to the analysis results, more data-
sets (DS 24,25) would have been in favour of GIC and
fewer in favour of resin if all sealed teeth that were lost
to follow-up were assumed to have developed caries in
their pits and fissures. How high the caries rate in the
teeth lost to evaluation really was remains unknown.
Owing to uncertainty regarding the real caries preva-
lence within those lost to follow-up, the results of the
sensitivity analysis cannot serve as evidence that GIC
would perform better than resin. However, the validity
of the four datasets (DS 06,12,24,25) can be questioned
on grounds of attrition bias and thus, their results need
to be regarded with caution.
None of these datasets were included into the meta-
analyses (Figure 2 and 3) and thus do not affect their
results. However, one dataset (DS 06) was also included
in the cumulative meta-analysis (Figure 4). A re-compu-
tation of the data including all loss-to-follow-up (under
assumption of caries) did not change the initially
observed trend. Rather, the trend was reinforced, as the
Figure 5 Funnel plot of dataset results (test for publication
bias). RR = Relative Risk.
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