Original Paper
Caries Res 2013;47:78–87
DOI: 10.1159/000344015
Surface-Specific Efficacy of Fluoride
Varnish in Caries Prevention in the
Primary Dentition: Results of a Community
Randomized Clinical Trial
K. Divaris a, b J.S. Preisser c G.D. Slade d
a
Department of Pediatric Dentistry, School of Dentistry, b Epidemiology and c Biostatistics, Gillings School of
Global Public Health, and d Department of Dental Ecology, School of Dentistry, University of North Carolina,
Chapel Hill, N.C., USA
Key Words
Community intervention  Dental caries  Enamel defects 
Fluoride varnish  Generalized estimating equations 
Hypoplastic teeth  Prevention  Randomized controlled
trials
Abstract
Objectives: Fluoride varnish (FV) is efficacious in caries pre-
vention although its effects among different tooth surfaces
are poorly understood. This study sought to determine the
extent to which caries-preventive effects of a community in-
tervention that included FV application among preschool-
aged children varied according to primary tooth anatomy
and baseline tooth pathology. Methods: Secondary analysis
was undertaken of data from a community-randomized con-
trolled trial among 543 3- to 5-year-old Aboriginal children
in 30 Northern Territory Australian communities. Children in
intervention communities received community health pro-
motion and FV application once every 6 months. Net caries
(d3mfs) risk and 95% confidence limits (CL) were estimated
for the control and intervention arms, and stratified accord-
© 2012 S. Karger AG, Basel
0008–6568/13/0471–0078$38.00/0
Fax +41 61 306 12 34
E-Mail karger@karger.ch Accessible online at:
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Received: August 16, 2011
Accepted after revision: October 4, 2012
Published online: November 27, 2012
ing to tooth anatomy/location and baseline pathology
(sound, enamel opacity, hypoplastic defect or precavitated
carious lesion). The intervention’s efficacy was quantified us-
ing generalized estimating equation modeling accounting
for study design and clustering. The assumption of efficacy
homogeneity was tested using a Wald 2 test with a p ! 0.2
criterion and post hoc pairwise comparisons. Results: The
intervention resulted in a 25% reduction (relative risk, RR =
0.75; 95% CL = 0.71, 0.80) in the 2-year surface-level caries
risk. There was substantial heterogeneity in FV efficacy by
baseline surface pathology: RRs were 0.73 for sound, 0.77 for
opaque, 0.90 for precavitated, and 0.92 for hypoplastic sur-
faces. Among sound surfaces, maxillary anterior facials re-
ceived significantly more benefit (RR = 0.62) compared to
pits and fissures (RR = 0.78). Conclusion: The intervention
had greatest efficacy on surfaces that were sound at base-
line. Among those sound surfaces, maxillary anterior facials
received most caries-preventive benefit.
Copyright © 2012 S. Karger AG, Basel
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Gary D. Slade
Department of Dental Ecology, Old Dental Building, Room 2100
CB#7450, School of Dentistry, University of North Carolina
Pontificia Universidad
Chapel Hill, NC 27599 (USA)
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E-Mail gary_slade @ dentistry.unc.edu
 Dental caries has multiple consequences for individu-
als, societies and health systems that have been described
by scientific and professional bodies, as well as policy
makers [Selwitz et al., 2007; Casamassimo et al., 2009].
There are compelling needs for discovery and implemen-
tation of efficacious and cost-effective primary preven-
tion measures, with children being the obvious and stra-
tegic target of most preventive efforts [Crall, 2007]. De-
spite major strides in our knowledge and understanding
of the etiology and pathogenesis of caries, the disease
continues to confer a significant public health burden in
many areas of the world [Petersen et al., 2005; Feather-
stone, 2009].
The distribution of caries in populations is character-
ized by marked inequalities, with a small proportion of
individuals bearing the biggest burden of the disease
[Pitts, 1998; Antunes et al., 2004; Pine et al., 2004]. With-
in individuals, caries is concentrated in terms of intraoral
location, severity, and aggressiveness of caries [Psoter et
al., 2003]. In the primary dentition, for example, molars
and hypoplastic surfaces are consistently reported to be
at greater risk for caries compared to lower incisors and
sound surfaces [Brown et al., 1996; Rethman, 2000]. To
make informed decisions about prevention and restor-
ative care, patients and their families, clinicians and re-
searchers need to understand children’s risk of develop-
ing caries and the factors that affect that risk. Because
different individuals, teeth, and surfaces may have sig-
nificantly variable risk of developing caries, it is impor-
tant for the purpose of both clinical treatment and public
health planning to identify those high- and low-risk
‘units’ – both children and teeth [Crall, 2007; Meurman
and Pienihäkkinen, 2010]. Likewise, to judge which chil-
dren and teeth are most likely to benefit from treatment,
it is valuable to understand factors underlying heteroge-
neity of caries-preventive measures.
Fluoride, in its various forms and delivery modalities,
has been the cornerstone of caries prevention for over half
a century [Featherstone, 2000]. Among professionally ap-
plied fluorides, fluoride varnish (FV) has been estab-
lished as a safe and effective chemopreventive agent, and
it is easily delivered by individuals other than dentists
and their staff. For this reason, FV application has be-
come an integral component of dental office-based pre-
ventive programs, and is been increasingly incorporated
in medical office and community-based interventions
that target early childhood caries [AAPD, 2010].
The caries-preventive efficacy and effectiveness of FV
has been long demonstrated and established by random-
ized controlled trials. A meta-analysis of FV efficacy re-
Surface-Specific Efficacy of Fluoride
Varnish
ported a summary estimate of 33% [Marinho et al., 2002]
for the caries prevented fraction in the primary dentition,
although the authors found that data in preschool popu-
lations are generally sparse [Azarpazhooh and Main,
2008; Marinho, 2009]. The efficacy of interventions in-
cluding FV in clinic-based settings falls in the range of
50–70% [Tewari et al., 1991; Weintraub et al., 2006].
Community-based trials usually evaluate effectiveness of
FV that is provided in conjunction with advice regarding
oral hygiene or diet, and the intervention is often evalu-
ated in population groups with historically high caries
rates. For example, in a Canadian community-random-
ized clinical trial, the prevented fraction ranged from 18
to 25%, varying according to ethnicity [Lawrence et al.,
2008].
Most evidence of FV caries-preventive efficacy comes
from observational studies of person-level caries risk or
increment, important metrics for determining efficacy,
equivalence, potential public health benefit, cost-effec-
tiveness, and more. Early observational and experimen-
tal investigations established the different effects of var-
ious forms of fluorides on different tooth surfaces [Mc-
Donald and Sheiham, 1992], confirming that smooth
surfaces receive more protective benefits compared to
occlusal ones [Backer Dirks et al., 1961]. This finding is
consistent with the different fluoride content in each sur-
face type (i.e. occlusal vs. smooth) [Candeli et al., 1970]
and has been replicated in experimental studies of both
fluoride mouthrinses [Ripa et al., 1985] and varnishes
[Koch and Petersson, 1975]. However, evidence is lacking
with regard to the caries-preventive efficacy of FV among
different types of primary teeth, based either on tooth
anatomy or existing pathology. The motivation for the
present study was to add to the knowledge base of FV ef-
ficacy, focusing on teeth and surfaces of different types
(pits and fissures, maxillary incisors, etc.) and on condi-
tions at baseline (i.e. sound, hypoplastic, precavitated
surfaces, etc.). Although caries is a person-level disease,
it should be expected that FV may confer different levels
of caries protection in surfaces with different caries risk
and fluoride retention potential. In fact, a recent study
indicated that genetically conferred caries risk may dif-
fer between pits and fissures and smooth surfaces in the
primary dentition [Shaffer et al., 2012]. Therefore, the
specific aim was to determine if the caries-preventive ef-
fect of a community intervention that included FV ap-
plication varied according to tooth anatomy and baseline
tooth pathology.
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 Materials and Methods
We undertook secondary analysis of data from a randomized
controlled trial in which oral health promotion and twice-per-
year application of FV was found to be efficacious in reducing
overall caries increment [Slade et al., 2011]. This secondary analy-
sis focused on caries increment of specific tooth surfaces.
Parent Study
We used data from a 2-year prospective cluster-randomized
trial that tested a dental preventive program among 30 Aborigi-
nal communities in Australia’s Northern Territory between
2006 and 2008. Full details of the trial, including CONSORT
specifications [Campbell et al., 2004], are provided at Slade et al.
[2011]. The study’s primary aim was to determine if an interven-
tion that included twice a year FV application and oral health
promotion reduced the incidence of caries in the primary denti-
tion of 666 2- to 4-year-old children over the 2-year study period.
In addition to the FV applications, the intervention included
training of primary care workers and health promotion for oral
health at an individual, family and community level. Communi-
ties in the intervention arm (n = 15) received two visits per year
over the study period, whereas control communities (n = 15)
were visited only twice, for clinical examinations at baseline and
2 years later. At each visit, study procedures were provided to all
children living in the community who were aged 18–47 months
and whose parents provided consent. Detailed reports on the
study design, clinical procedures and primary outcomes have
been published previously [Slade et al., 2011]. In brief, although
the intervention did not result in any significant change in oral
health behaviors, clinical measures of oral hygiene, or commu-
nity programs promoting oral health [Roberts-Thomson et al.,
2010], children in the intervention communities experienced a
significantly smaller mean caries increment than in the control
communities, a relative reduction of approximately 30% [Slade
et al., 2011].
Clinical Examinations
Trained clinical examiners carried out the clinical exams us-
ing artificial light and visual criteria after drying of the teeth with
absorbent paper. Unerupted teeth were distinguished from teeth
that were missing or extracted teeth due to caries. Each visible
tooth surface was assigned one of eight diagnosis codes, with the
most severe being recorded if two or more conditions coexisted:
sound, opacity, hypoplastic enamel loss, precavitated carious le-
sion, cavitated carious lesion (d3), arrested carious lesion, re-
stored. The examiners followed prespecified criteria for the diag-
nosis of all lesions. Opacity was specifically defined as discolor-
ation of the enamel creating a ‘chalky’ appearance, with reduced
translucency (i.e. ‘gloss’) of the enamel surface, not due to caries.
Hypoplastic loss of enamel was defined as one of the following, in
the absence of caries: localized reduction in the thickness of
enamel, single or multiple pits that may be shallow or deep, scat-
tered, or in rows arranged horizontally across the tooth surface,
single or multiple grooves that may vary in width, and partial or
complete absence of enamel over a considerable area of dentine.
A precavitated lesion was recorded when there was a discoloration
of enamel that was due to initial caries, while the enamel surface
remained intact, and had all of the following features: no evidence
of cavitation, near the gingival margin in a caries-susceptible
80 Caries Res 2013;47:78–87
area, at least 1 mm thick, typically of crescent shape, conforming
with the position on enamel where plaque typically accumulates,
and opaque color, leaving a chalky appearance that may be off-
white or a darker color if extrinsic strains had been absorbed into
the lesion.
Four trained examiners carried out both baseline and follow-
up examinations. To evaluate interexaminer reliability there
were 13 children at baseline and 21 at follow-up that were repeat-
edly examined by the 4 examiners and a gold standard examiner.
As previously reported, when dental caries was classified at the
cavitation threshold, the surface-level interexaminer reliability
estimate at baseline was kappa = 0.80 (95% confidence limits,
CL = 0.72, 0.87), with individual kappas between examiners and
gold standard ranging from 0.73 to 0.83. At follow-up, these esti-
mates were kappa = 0.83 (95% CL = 0.80, 0.87), with a range of
0.68–0.90. For this investigation, we reanalyzed the examiner re-
liability data after disaggregating lesions that do not represent
cavitation-level caries, which was the threshold used to report
reliability in Slade et al. [2011]. There were 2,888 surfaces that
were classified either as sound, opaque, hypoplastic or precavi-
tated by the gold-standard examiner (n = 2,806, 36, 30 and 16
surfaces, respectively) and by the study examiner(s). The un-
weighted kappa statistic was 0.50 (95% CL = 0.41, 0.59), indicat-
ing moderate agreement between the gold-standard examiner
and the study examiner.
Analytical Strategy
The analytical endpoint of the present analysis is surface-level
caries risk, evaluated at the cavitation (d3), restoration or extrac-
tion level. There were 543 children with clinical data from both
baseline and 2-year follow-up examinations. At each exam, each
tooth surface (up to 100 per child) was classified according to the
most severe condition diagnosed, using the following ascending
order of tooth pathology: sound surface, opacity, hypoplastic
enamel loss, precavitated lesion (d1), cavitated lesion (d3), restora-
tion, extracted, or missing and unavailable. The anatomy of each
tooth surface was further classified according to three features:
(a) tooth location (anterior = incisors or canines; posterior = mo-
lars); (b) surface anatomy (facial, lingual, occlusal and proximal);
(c) subclassifications of both tooth location and surface anatomy
(posterior teeth, maxillary anterior teeth, occlusal surfaces, pits
and fissures, maxillary anterior facial surfaces and proximal sur-
faces). Additional information collected was children’s sex and
age, as well as community water fluoride level (measured in ppm
F– and coded as a dichotomous variable with a 60.6 ppm thresh-
old in bivariate analyses, and as a continuous variable in multi-
variate analyses).
Descriptive methods were used to present and inspect child-
level demographic characteristics, community water fluoride lev-
els, as well as tooth- and surface-level baseline diagnoses. Differ-
ences in age, sex and water fluoridation between children in the
two experimental arms were tested with 2 tests of equivalence
and a p ! 0.05 threshold. To illustrate the distribution of surface-
level diagnoses and their transition from baseline to follow-up we
constructed a DePaola [1990] transition grid. Transition from
sound, opaque, hypoplastic or precavitated status to decayed,
filled, arrested or extracted was recorded as (crude) caries incre-
ment, whereas the inverse biologically implausible transition as a
caries decrement. As an approach for correcting for these ‘exam-
iner reversals’ we computed ‘net’ caries risk (2-year cumulative
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incidence) by subtracting reversals from the crude increment
[Horowitz et al., 1973; Slade and Caplan, 2000]. To estimate net
increment-based risk (cumulative incidence and 95% CL) we
computed net increment means and 95% CL, correcting for study
design and clustering of observations within children and com-
munities. We note that the 95% CL represent the upper and lower
bounds of the corresponding 95% confidence intervals.
FV efficacy was determined by the contrast between experi-
mental arm estimates, overall and stratified by tooth anatomy and
baseline pathology. Specifically, relative risk (RR) and 95% CL
were estimated using a novel implementation of generalized esti-
mating equations for net caries modeling, described in the appen-
dix. Conditioning on baseline surface status, this used a log link
generalized linear model that explicitly modeled increments and
decrements (binary outcome), and a log odds ratio model [Carey
et al., 1993] to account for the nested covariance structure (tooth
surfaces clustered within levels of children and communities). Be-
cause community water fluoride levels were unbalanced between
the two experimental arms we developed a second series of
models controlling for this variable to obtain ‘adjusted’ RR and
95% CL.
To determine whether baseline pathology and tooth anatomy
modified the FV efficacy we compared stratum-specific esti-
mates using empirical methods (inspection) and formal testing
of effect measure modification. Strata were the baseline diagno-
ses, tooth positions and surface locations described above. Sub-
sequently, we conducted a global Wald 2 test of ‘common esti-
mate’ (across-strata homogeneity) using a conservative p ! 0.2
threshold [Greenland and Rothman, 2008]. Further, we comput-
ed between-strata post hoc pairwise comparison Z scores and
corresponding p values to identify strata that departed from ho-
mogeneity. The rationale for conducting comparisons of stra-
tum-specific estimates instead of evaluating effect measure mod-
ification in the context of statistical interaction is based on the
fact that the former approach does not assume covariate effect
homogeneity across strata (i.e. community water fluoride levels
may exert different caries-preventive effects on different tooth/
surface types). This could introduce non-negligible bias when es-
timating weak ‘main’ effects in the presence of strong confound-
ers. In the context of statistical interaction, however, the intro-
duction of main effect and all covariate interaction terms is un-
common and likely inefficient. All analyses were conducted with
SAS 9.2 (SAS Institute, Cary, N.C., USA).
Results
Children’s median age at the 2-year follow-up was 58
months (range 42–71 months) (table 1). Optimal commu-
nity water fluoridation was uncommon (13% of children),
but children in the control group were more than twice
as likely to be living in optimally fluoridated communi-
ties (19 vs. 8%, p ! 0.05). At baseline, 14% of examined
teeth had caries, but there were no restorations. Smaller
proportions of teeth were precavitated (6.4%) or had hy-
poplastic defects (4.6%). Almost 80% of examined sur-
faces were classified as sound at baseline.
Surface-Specific Efficacy of Fluoride
Varnish
At follow-up, most sound surfaces remained sound,
and approximately 6% were diagnosed as carious (ta-
ble 2). Higher proportions of opaque (15%), precavitated
(22%) and hypoplastic (30%) surfaces developed caries
(d3ef) during the study period, however, sound surfaces
accounted for 81% of that crude increment (3,820/4,724
surfaces). Considering child-level caries diagnoses, the
majority of children (65%) had already caries (d3efs 10)
at baseline, and virtually all (94%) had caries at follow-up.
Of note is the proportion of ‘examiner reversals’ that can
be directly estimated from the transition grid; 10% of
cavitated surfaces (n = 250) at baseline were recorded as
sound at follow-up and 2% (n = 49) were classified as hy-
poplastic at follow-up. Moreover, a substantial propor-
tion of 28% of surfaces (n = 184) diagnosed as having hy-
poplastic loss of enamel at baseline were recorded as
sound at follow-up.
Based on the overall, net caries increment for all teeth
and tooth surfaces, the risk of caries in the FV group rel-
ative to the control group was 0.79 (95% CL = 0.74, 0.84),
equivalent to a 21% reduction in incidence of caries (ta-
ble 3). This reduction was 25% (i.e. RR = 0.75, 95% CL =
0.71, 0.80) after adjustment for community water fluori-
dation, while the surface-level 2-year caries risk among
control and intervention communities was 10.7 and 8.2%,
respectively. Of note, sound surfaces received slightly
more benefit in relative terms (RR = 0.73) compared to
opaque surfaces (RR = 0.77), whereas RRs were closer to
the null and more imprecise for precavitated and hypo-
plastic surfaces. There was strong evidence against the
assumption of homogeneity of RRs according to baseline
pathology (Wald 2 = 10.2, d.f. = 3, p ! 0.05). This was
confirmed with post hoc pairwise comparisons, where
the estimates among hypoplastic and precavitated sur-
faces were weaker compared to those among sound sur-
faces. With regard to tooth anatomy, posterior teeth and
pits and fissures received more benefit compared to max-
illary anterior facial surfaces, but these differences were
small. Indeed, we found no strong evidence of effect mea-
sure modification according to tooth anatomy (Wald
2 = 1.6, d.f. = 4, p 1 0.2). Among sound surfaces at base-
line (79% of all surfaces), maxillary anterior facial sur-
faces received most benefit (RR = 0.62, 95% CL = 0.49,
0.77) compared to pits and fissures, which received the
least (RR = 0.78, 95% CL = 0.67, 0.90), Zhomogeneity = 1.67,
p = 0.05 (table 4).
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 Table 1. Demographic and dentition characteristics of the 3- to 5-year-olds participating in the ‘Strong Teeth
for Little Kids’ community cluster-randomized trial among Australian Aboriginal children (2006–2008), for
whom baseline and follow-up examinations were available (n = 543)

Total Control Intervention

Demographics
Sex
Male 274 (50.5) 138 (52.7) 136 (48.4)
Female 269 (49.5) 124 (47.3) 145 (51.6)
Age at follow-up, years
Mean 8 SD 57.588.5 56.988.3 58.088.7
Median (range) 58 (42–71) 57 (42–71) 59 (42–71)
Age group
41–59 months 289 (53.2) 147 (56.1) 142 (50.5)
60–72 months 254 (46.8) 115 (43.9) 139 (49.5)
Fluoride concentration in community water
<0.6 ppm F– 472 (86.9) 214 (81.7) 258 (91.8)
≥0.6 ppm F– 71 (13.1) 48 (18.3) 23 (8.2)
Dentition status at baseline
Tooth-level diagnoses1
Sound 5,886 (53.6) 2,777 (52.4) 3,109 (54.7)
Opacity 1,452 (13.2) 719 (13.6) 733 (12.9)
Hypoplasia 519 (4.7) 263 (5.0) 256 (4.5)
Precavitated (d1) 700 (6.4) 367 (6.9) 333 (5.6)
Cavitated (d3) 1,489 (13.6) 719 (13.6) 770 (13.5)
Arrested caries 109 (1.0) 43 (0.8) 66 (1.2)
Extracted 10 (0.1) 7 (0.1) 3 (0.1)
Unerupted 818 (7.4) 405 (7.6) 413 (7.3)
Total 10,983 5,300 5,683
Surface-level diagnoses
Sound 43,046 (79.3) 20,768 (79.3) 22,278 (79.3)
Opacity 1,752 (3.2) 912 (3.5) 840 (3.0)
Hypoplasia 661 (1.2) 345 (1.3) 316 (1.1)
Precavitated (d1) 738 (1.4) 389 (1.5) 349 (1.2)
Cavitated (d3) 2,395 (4.4) 1,128 (4.3) 1,267 (4.5)
Arrested caries 193 (0.4) 93 (0.4) 100 (0.4)
Extracted 50 (0.1) 35 (0.1) 15 (0.05)
Unerupted 4,090 (7.5) 2,025 (7.7) 2,065 (7.3)
Unable to assess 1,375 (2.5) 505 (1.9) 870 (3.1)
Total 54,300 26,200 28,100
1 Column figures do not add up to total: more than one surface-level diagnosis per tooth may be recorded;

sound teeth are not shown. Figures in parentheses are percentages unless specified otherwise.

Discussion to tooth anatomy when considering all surfaces, with any

This study’s findings add to the accumulating body of
evidence demonstrating the efficacy of FV in preventing
caries in the primary dentition. Our results indicate that
sound surfaces, while having lower caries risk compared
to surfaces with baseline pathology, received the greatest
relative benefit from FV applications. There was no sig-
nificant degree of effect measure modification according
baseline diagnosis. However, among surfaces that were
sound at baseline, maxillary anterior facial surfaces re-
ceived significantly more benefit from FV, in relative
terms, compared to pits and fissures.
Although the reported differences are not great in
magnitude, the heterogeneity was demonstrable. The
heterogeneity of FV efficacy can be attributed to the dif-
ferences in baseline risk and enamel properties between
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Table 2. Transition grid displaying the classification (n, row %) of surface-level diagnoses at baseline and follow-up (2-year) examina-
tions of the 3- to 5-year-olds participating in the ‘Strong Teeth for Little Kids’ community cluster-randomized trial among Australian
Aboriginal children (2006–2008), for whom baseline and follow-up examinations were available (n = 543)

Follow-up tooth surface-level diagnoses

sound opacity hypo- precavitated carious (d3) arrested filled extracted un- un- total
plastic (d1) erupted available

Baseline tooth surface-level diagnoses1

Sound 36,555 (84.9) 913 (2.1) 471 (1.1) 1,124 (2.6) 2,515 (5.8) 638 (1.5) 273 (0.6) 394 (0.9) 127 (0.3) 36 (0.1) 43,046
Opacity 811 (46.3) 223 (12.7) 134 (7.6) 183 (10.4) 263 (15.0) 82 (4.7) 41 (2.3) 12 (0.7) 3 (0.2) 0 (0) 1,752
Hypoplastic 184 (27.8) 45 (6.8) 127 (19.2) 19 (2.9) 201 (30.4) 43 (6.5) 17 (2.6) 21 (3.2) 4 (0.6) 0 (0) 661
Caries d1 308 (41.7) 27 (3.7) 31 (4.2) 146 (19.8) 163 (22.1) 49 (6.6) 3 (0.4) 9 (1.2) 2 (0.3) 0 (0) 738
Caries d3 250 (10.4) 7 (0.3) 49 (2.1) 16 (0.7) 1,261 (52.7) 366 (15.3) 90 (3.8) 325 (13.6) 31 (1.3) 0 (0) 2,395
Arrested 30 (15.5) 2 (1.0) 2 (1.0) 1 (0.5) 64 (33.2) 78 (40.4) 9 (4.7) 4 (2.1) 3 (1.5) 0 (0) 193
Extracted 5 (10.0) 0 (0) 0 (0) 0 (0) 5 (10.0) 0 (0) 0 (0) 25 (50.0) 15 (30.0) 0 (0) 50
Unerupted 2,953 (72.2) 322 (7.9) 142 (3.5) 226 (5.5) 331 (8.1) 55 (1.3) 36 (0.9) 15 (0.4) 10 (0.2) 0 (0) 4,090
Unavailable 942 (68.5) 43 (3.1) 42 (3.1) 45 (3.3) 191 (13.9) 15 (1.1) 7 (0.5) 45 (3.3) 40 (2.9) 5 (0.4) 1,375
Total 42,038 1,582 998 1,760 4,994 1,326 476 850 235 41 54,300
1
At baseline there were no filled surfaces.

Table 3. Net 2-year surface-level cavitation risk estimates (cumulative incidence and 95% CL) for sound, opaque, hypoplastic and pre-
cavitated surfaces at baseline among the total study sample of 3- to 5-year-olds, and stratified by experimental group and intervention
efficacy estimates (RR and 95% CL) in the ‘Strong Teeth for Little Kids’ community-randomized trial (2006–2008) among Australian
Aboriginal children (n = 543)

Control group Intervention group Unadjusted efficacy Adjusted efficacy1

cumulative incidence cumulative incidence RR RR
(95% CL) (95% CL) (95% CL) (95% CL)

Overall 0.107 (0.096, 0.118) 0.082 (0.074, 0.090) 0.79 (0.74, 0.84) 0.75 (0.71, 0.80)
Baseline surface status
Sound 0.094 (0.084, 0.105) 0.070 (0.063, 0.078) 0.77 (0.72, 0.83) 0.73 (0.69, 0.79)
Opaque 0.236 (0.203, 0.269) 0.206 (0.173, 0.239) 0.82 (0.69, 0.98) 0.77 (0.65, 0.92)
Hypoplastic 0.311 (0.217, 0.405) 0.343 (0.280, 0.406) 0.97 (0.81, 1.17) 0.90 (0.75, 1.08)
Precavitated 0.287 (0.228, 0.347) 0.261 (0.207, 0.315) 0.99 (0.79, 1.24) 0.92 (0.74, 1.15)
Tooth/surface type
Posterior teeth 0.133 (0.116, 0.149) 0.094 (0.083, 0.105) 0.74 (0.66, 0.83) 0.72 (0.64, 0.80)
Pits and fissures 0.247 (0.220, 0.274) 0.184 (0.161, 0.206) 0.78 (0.69, 0.89) 0.75 (0.66, 0.86)
Occlusal surfaces 0.258 (0.229, 0.287) 0.188 (0.163, 0.213) 0.78 (0.68, 0.91) 0.76 (0.66, 0.89)
Maxillary anterior teeth 0.165 (0.146, 0.185) 0.131 (0.115, 0.146) 0.83 (0.77, 0.90) 0.77 (0.71, 0.83)
Maxillary anterior facials 0.237 (0.206, 0.268) 0.195 (0.168, 0.221) 0.85 (0.73, 0.98) 0.78 (0.67, 0.91)
Proximal surfaces 0.084 (0.073, 0.096) 0.070 (0.062, 0.079) 0.86 (0.77, 0.95) 0.78 (0.71, 0.87)
1
Adjusted for community water fluoride level.

different surface groups. In this study, for example, hypo-
plastic and precavitated surfaces had approximately two
times higher cavitation risk compared to sound ones.
Previous prospective and case control studies have re-
ported on the strong association between enamel hypo-
plastic defects and caries incidence [Milgrom et al., 2000;
Oliveira et al., 2006; Hong et al., 2009; Seow et al., 2009;
Farsi, 2010; Targino et al., 2011]. Compromised enamel
may be more prone to harbor cariogenic microflora [Li et
al., 1994, 1996] and less receptive to the beneficial remin-
eralizing effects of fluoride [ten Cate, 1999], a mechanism
that could explain both the high caries risk and the re-
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Table 4. Net 2-year surface-level cavitation risk estimates (cumulative incidence and 95% CL) for sound surfaces at baseline among the
total study sample of 3- to 5-year-olds, and stratified by experimental group and intervention efficacy estimates (RR and 95% CL) in
the ‘Strong Teeth for Little Kids’ community-randomized trial (2006–2008) among Australian Aboriginal children (n = 543)

Control group Intervention group Unadjusted efficacy Adjusted efficacy1

cumulative incidence cumulative incidence RR RR
(95% CL) (95% CL) (95% CL) (95% CL)

Sound surfaces at baseline 0.094 (0.084, 0.105) 0.070 (0.063, 0.078) 0.77 (0.72, 0.83) 0.73 (0.69, 0.79)
By tooth/surface/type
Posterior teeth 0.122 (0.106, 0.138) 0.087 (0.076, 0.097) 0.75 (0.67, 0.84) 0.73 (0.65, 0.82)
Pits and fissures 0.222 (0.196, 0.249) 0.170 (0.147, 0.193) 0.81 (0.70, 0.93) 0.78 (0.67, 0.90)
Occlusal surfaces 0.238 (0.209, 0.268) 0.176 (0.150, 0.202) 0.81 (0.69, 0.95) 0.78 (0.66, 0.91)
Maxillary anterior teeth 0.147 (0.129, 0.164) 0.111 (0.097, 0.125) 0.81 (0.73, 0.88) 0.74 (0.67, 0.81)
Maxillary anterior facials 0.172 (0.143, 0.201) 0.118 (0.093, 0.143) 0.66 (0.53, 0.83) 0.62 (0.49, 0.77)
Proximal surfaces 0.083 (0.071, 0.094) 0.066 (0.058, 0.075) 0.84 (0.75, 0.93) 0.76 (0.68, 0.84)
1 Adjusted for community water fluoride level.

duced caries-protective FV benefit. On the other hand,
enamel hypoplastic lesions comprise a markedly diverse
group of anatomic defects that may have substantially
different surface properties but may be very hard or im-
possible to differentiate clinically [Hillson and Bond,
1997; Seow, 1997]. It must also be noted that the study’s
power to detect differences in FV efficacy was limited due
to the relatively small prevalence of these lesions: opaci-
ties (3%), hypoplastic enamel loss (1%), and precavitated
surfaces (1%).
With regard to enamel opacities, it is likely that this
diagnostic classification also represents a heterogeneous
group of isolated enamel disturbances such as diffuse or
demarcated opacities, and demineralizations [Ellwood
and O’Mullane, 1996; Slayton et al., 2001]. In our cohort,
the prevalence of teeth with opacities (13%) and hypo-
plastic defects (5%) was lower compared to 27 and 6%,
respectively, that was reported by Slayton et al. [2001].
Likewise, prevalence of opacities and hypoplastic lesions
was lower here than in other studies of developmentally
challenged children [Velló et al., 2010; Lin et al., 2011].
Interestingly, in the study by Lai et al. [1997] a phenotype
with enamel hypoplasia and opacities was the one most
strongly associated with subsequent caries development.
More recently, Nelson et al. [2010] reported that demar-
cated opacities were significant predictors of molar and
incisor caries among adolescents. Another consideration
is that misclassification between these baseline patholo-
gies may be substantial.
Psoter et al. [2003] reported that early childhood caries
can be classified in four distinct disease patterns accord-
ing to tooth surfaces affected, i.e. maxillary incisor sur-
faces and pits and fissures. This was consistent with pre-
vious epidemiological findings [O’Sullivan and Tinanoff,
1993; Brown et al., 1996; Rethman, 2000]. In the present
trial, pits and fissures, proximal, as well as maxillary an-
terior facial surfaces had approximately 25% risk of caries
over the 2-year study period. In spite of this, the FV ef-
ficacy showed little variation between different tooth/
surface types, ranging between 22 and 28%.
It was noteworthy that the relative reduction in caries
due to FV was greatest for sound surfaces, despite them
having the lowest caries risk. Even among the pitted and
fissured sound surfaces, efficacy was greater than in hy-
poplastic or precavitated surfaces. This is consistent with
early observations of Backer Dirks et al. [1961], who sug-
gested that the surface-specific caries-preventive efficacy
of water fluoridation on permanent teeth was ‘correlated
with the degree to which fluoride ions can be built in or
absorbed by the enamel on these surface’. These findings
have important clinical and public health implications.
In this age group, no more than 0.25 ml of FV per child
should be used, and it is therefore common to assign pri-
ority to specific teeth when applying FV. In resource-lim-
ited settings and based on these findings, net caries-pre-
ventive benefit would be maximized by assigning greatest
priority during FV application to surfaces that appear
sound, rather than surfaces that have visible loss of enam-
el (classified here as hypoplastic or precavitated). None-
theless, it is clear that these interventions were not a
panacea for caries in these remote communities that ex-
perience extremely high rates of dental caries and socio-
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84 Caries Res 2013;47:78–87 Divaris /Preisser /Slade

     
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economic disadvantage. As we have noted previously, ‘it
would be naïve to believe that these Australian Aborigi-
nal children could be “immunized” against caries’ [Slade
et al., 2011].
The estimation of caries risk using net increment is
considered an improvement over the crude increment
[Bell and Klein, 1984; Beck et al., 1995], because the latter
is naïve to examiner misclassification (‘reversals’). In this
study, reversals of carious surfaces (d3) at baseline to sound
at follow-up were observed with a frequency of 10.4%.
Beck et al. [1995] and more recently Ismail et al. [2011] have
introduced formulae and recommended the use of ‘adjust-
ed’ increments, as a less penalizing way of correcting for
these biologically implausible transitions. Beck et al. [1995]
recommended the use of adjusted increments particularly
when the frequency of reversals exceeds 10%. Although
reversal of cavitated surfaces to sound were slightly above
that threshold in the parent study (10.4%) we did not con-
sider adjusted increments for the present analysis. On the
other hand, the adjusted increment of Beck et al. [1995]
was found to be similar to the net increment among chil-
dren [Slade and Caplan, 2000]. With regard to reasons be-
hind the observed ‘reversals’, it can be argued that some
level of measurement error is unavoidable in clinical stud-
ies, particularly the ones on the field.
In summary, a community intervention among Aus-
tralian Aboriginal 2- to 4-year-old children which in-
cluded twice a year FV application reduced the surface-
level 2-year caries risk by 25%. The intervention had
greatest efficacy on surfaces that were sound at baseline.
Despite variations in caries risk, efficacy was relatively
homogeneous across different tooth types. Among sound
surfaces, however, maxillary anterior facial surfaces re-
ceived most caries-preventive benefit.
Appendix
For a given surface, let t0 and t1 be dichotomous variables for
the presence of caries at baseline and follow-up, respectively, each
taking values 1 = present, 0 = absent. The net caries increment is
defined as
 = p1 (1 – pd)
where p1 = P (t1 = 1t0 = 0) is the probability of an increment and
pd = P (t1 = 0t0 = 1) is the probability of a reversal (nonplausible
decrement). Further, let p2 = P (t1 = 1t0 = 1) be the probability of
a surface carious at baseline remaining carious at follow-up, not-
ing that p2 = 1 – pd. Conditioning on t0, all available surface-level
data (consisting of the four possible transitions between healthy
and carious conditions between baseline and follow-up) are used
to model the probability of a surface having caries at follow-up (p1
Surface-Specific Efficacy of Fluoride
Varnish
or p2 depending upon baseline caries status) with a no-intercept
log link generalized linear model for t1:
log[P(t1 = 1t0)] = (1 – t0) [10 + 11X] + t0 [20 + 21X]
where X denotes one or more surface-level or subject-level covari-
ates, 10 denotes the log-risk for increments among those with
X = 0, 11 is the change in log-risk for increments with a one-unit
change in X, 20 denotes the log-risk for remaining carious over
time, while 21 is the change in log-risk for remaining carious
with a one-unit change in X.
The model above gives p1 = exp(10 + 11X) and p2 =
exp(20 + 21X). Thus, the model for  = p1p2 is
log = 0 + 1X
where 0 = 10 + 20 and 1 = 11 + 21 so that the exp(1) repre-
sents the RR, more specifically the multiplicative increase on the
net caries increment for a unit change in X. For a given set of co-
variates, X, the net caries increment (cumulative incidence) is es-
ˆ 10 + 
timated by ˆ = exp[( ˆ 20) + (
ˆ 11 + 
ˆ 21)X] and a 95% confidence
interval is exp[logˆ + 1.96 se(logˆ)] where vˆ ar (logˆ) = se2(logˆ)
is a function of the covariance matrix of the estimate’s regression
parameters  ˆ as determined from the delta method [Agresti,
2002]. Confidence intervals for RR are similarly constructed.
To adjust for the nested covariance structure, a three-level log
odds ratio model [see eq. 3 of Preisser et al., 2003] was used to al-
low the clustering of observations within subjects to differ in
magnitude from the level of clustering of subjects (or subclusters)
within communities (or clusters). Empirical sandwich variance
estimators were used to provide robustness against misclassifica-
tion of the covariance structure.
Acknowledgments
The ‘Strong Teeth for Little Kids’ Project was supported by
grant No. 320858 from the Australian National Health and Med-
ical Research Council.
Disclosure Statement
Colgate-Palmolive Pty Limited provided free supplies of Du-
raphat varnish used in this study, and they provided low-cost
toothbrushes and toothpaste to community stores. None of the
authors or study personnel received or receive consulting pay-
ments or any other form of personal benefit from Colgate-Palmo-
live Pty Limited.
References Agresti A: Categorical Data Analysis, ed 2.
Hoboken, Wiley & Sons, 2002.
American Academy of Pediatric Dentistry
(AAPD): Guideline on caries-risk assessment
and management for infants, children, and
adolescents. 2010. Available at: http://www.
aapd.org/media/Policies_Guidelines/G_
CariesRiskAssessment.pdf (accessed July 7,
2011).
200.3.152.96 - 11/16/2022 5:08:35 PM
Caries Res 2013;47:78–87 85
Pontificia Universidad
Downloaded by:
Antunes JL, Narvai PC, Nugent ZJ: Measuring
inequalities in the distribution of dental car-
ies. Community Dent Oral Epidemiol 2004;
32:41–48.
Azarpazhooh A, Main PA: Fluoride varnish in
the prevention of dental caries in children
and adolescents: a systematic review. J Can
Dent Assoc 2008;74:73–79.
Backer Dirks O, Houwink B, Kwant GW: Some
special features of the caries preventive effect
of water-fluoridation. Arch Oral Biol 1961;4:
187–192.
Beck JD, Lawrence HP, Koch GG: A method for
adjusting caries increments for reversals due
to examiner misclassification. Community
Dent Oral Epidemiol 1995;23:321–330.
Bell RM, Klein SP: Management and evaluation of
the effects of misclassification in a controlled
clinical trial. J Dent Res 1984;63:731–735.
Brown LJ, Kaste LM, Selwitz RH, Furman LJ:
Dental caries and sealant usage in U.S. chil-
dren, 1988–1991: selected findings from the
Third National Health and Nutrition Exam-
ination Survey. J Am Dent Assoc 1996; 127:
335–343.
Campbell MK, Elbourne DR, Altman DG; CON-
SORT group: CONSORT statement: exten-
sion to cluster randomised trials. BMJ 2004;
328:702–708.
Candeli A, Scavizzi F, Marci F: The relationship
between fluoride concentration and the car-
ies frequency of different tooth surfaces in a
high fluoride area. Caries Res 1970;4:69–77.
Carey V, Zeger SL, Diggle P: Modelling multi-
variate binary data with alternating logistic
regressions. Biometrika 1993; 80:517–526.
Casamassimo PS, Thikkurissy S, Edelstein BL,
Maiorini E: Beyond the dmft: the human and
economic cost of early childhood caries. J
Am Dent Assoc 2009;140:650–657.
Crall JJ: Optimising oral health throughout
childhood: the importance of caries risk as-
sessment and strategic interventions. Int
Dent J 2007;57:221–226.
DePaola PF: Measurement issues in the epide-
miology of dental caries; in Bader JD (ed):
Risk Assessment in Dentistry. University of
North Carolina-Chapel Hill, Dental Ecolo-
gy, 1990, pp 19–26.
Ellwood RP, O’Mullane D: The association be-
tween developmental enamel defects and
caries in populations with and without fluo-
ride in their drinking water. J Public Health
Dent 1996;56:76–80.
Farsi N: Developmental enamel defects and their
association with dental caries in preschool-
ers in Jeddah, Saudi Arabia. Oral Health
Prev Dent 2010;8:85–92.
Featherstone JD: The science and practice of car-
ies prevention. J Am Dent Assoc 2000; 131:
887–899.
Featherstone JD: Remineralization, the natural
caries repair process – the need for new ap-
proaches. Adv Dent Res 2009;21:4–7.
86 Caries Res 2013;47:78–87
Greenland S, Rothman KJ: Introduction to strat-
ified analysis; in Rothman KJ, Greenland S,
Lash TL (eds): Modern Epidemiology. New
York, Lippincott, Williams & Wilkins, 2008,
pp 258–282.
Hillson S, Bond S: Relationship of enamel hypo-
plasia to the pattern of tooth crown growth:
a discussion. Am J Phys Anthropol 1997;104:
89–103.
Hong L, Levy SM, Warren JJ, Broffitt B: Associa-
tion between enamel hypoplasia and dental
caries in primary second molars: a cohort
study. Caries Res 2009;43:345–353.
Horowitz HS, Baume LJ, Dirks OB, Davies GN,
Slack GL: Principal requirements for con-
trolled clinical trials of caries preventive
agents and procedures. Int Dent J 1973; 23:
506–529.
Ismail AI, Lim S, Sohn W: A transition scoring
system of caries increment with adjustment
of reversals in longitudinal study: evalua-
tion using primary tooth surface data.
Community Dent Oral Epidemiol 2011; 39:
61–68.
Koch G, Petersson LG: Caries preventive effect
of a fluoride-containing varnish (Duraphat)
after 1 year’s study. Community Dent Oral
Epidemiol 1975;3:262–266.
Marinho VC: Cochrane reviews of randomized
trials of fluoride therapies for preventing
dental caries. Eur Arch Paediatr Dent 2009;
10:183–191.
Marinho VC, Higgins JP, Logan S, Sheiham A:
Fluoride varnishes for preventing dental car-
ies in children and adolescents. Cochrane
Database Syst Rev 2002;3:CD002279.
Meurman PK, Pienihäkkinen K: Factors associ-
ated with caries increment: a longitudinal
study from 18 months to 5 years of age. Car-
ies Res 2010;44:519–524.
Milgrom P, Riedy CA, Weinstein P, Tanner AC,
Manibusan L, Bruss J: Dental caries and its
relationship to bacterial infection, hypopla-
sia, diet, and oral hygiene in 6- to 36-month-
old children. Community Dent Oral Epide-
miol 2000;28:295–306.
Nelson S, Albert JM, Lombardi G, Wishnek S,
Asaad G, Kirchner HL, Singer LT: Dental car-
ies and enamel defects in very low birth
weight adolescents. Caries Res 2010;44: 509–
518.
Lai PY, Seow WK, Tudehope DI, Rogers Y: Enam-
el hypoplasia and dental caries in very-low
birthweight children: a case-controlled, lon-
gitudinal study. Pediatr Dent 1997;19:42–49.
Lawrence HP, Binguis D, Douglas J, McKeown L,
Switzer B, Figueiredo R, Laporte A: A 2-year
community-randomized controlled trial of
fluoride varnish to prevent early childhood
caries in Aboriginal children. Community
Dent Oral Epidemiol 2008;36:503–516.
Li Y, Navia JM, Bian JY: Caries experience in de-
ciduous dentition of rural Chinese children
3–5 years old in relation to the presence or
absence of enamel hypoplasia. Caries Res
1996;30:8–15.
Li Y, Navia JM, Caufield PW: Colonization by
mutans streptococci in the mouths of 3- and
4-year-old Chinese children with or without
enamel hypoplasia. Arch Oral Biol 1994; 39:
1057–1062.
Lin X, Wu W, Zhang C, Lo EC, Chu CH, Dis-
sanayaka WL: Prevalence and distribution of
developmental enamel defects in children
with cerebral palsy in Beijing, China. Int J
Paediatr Dent 2011;21:23–28.
McDonald SP, Sheiham A: The distribution of
caries on different tooth surfaces at vary-
ing levels of caries – a compilation of data
from 18 previous studies. Community Dent
Health 1992;9:39–48.
Oliveira AF, Chaves AM, Rosenblatt A: The in-
fluence of enamel defects on the develop-
ment of early childhood caries in a popula-
tion with low socioeconomic status: a longi-
tudinal study. Caries Res 2006;40:296–302.
O’Sullivan DM, Tinanoff N: Maxillary anterior
caries associated with increased caries risk
in other primary teeth. J Dent Res 1993; 72:
1577–1580.
Petersen PE, Bourgeois D, Ogawa H, Estupinan-
Day S, Ndiaye C: The global burden of oral
diseases and risks to oral health. Bull World
Health Organ 2005;83:661–669.
Pine CM, Adair PM, Petersen PE, Douglass C,
Burnside G, Nicoll AD, Gillett A, Anderson
R, Beighton D, Jin-You B, Broukal Z, Brown
JP, Chestnutt IG, Declerck D, Devine D, Es-
pelid I, Falcolini G, Ping FX, Freeman R,
Gibbons D, Gugushe T, Harris R, Kirkham J,
Lo EC, Marsh P, Maupomé G, Naidoo S, Ra-
mos-Gomez F, Sutton BK, Williams S: De-
veloping explanatory models of health in-
equalities in childhood dental caries. Com-
munity Dent Health 2004;21:86–95.
Pitts NB: Inequalities in children’s caries ex-
perience: the nature and size of the UK
problem. Community Dent Health 1998;
15: 296–300.
Preisser JS, Arcury TA, Quandt SA: Detecting
patterns of occupational illness clustering
with alternating logistic regressions applied
to longitudinal data. Am J Epidemiol 2003;
158:495–501.
Psoter WJ, Zhang H, Pendrys DG, Morse DE,
Mayne ST: Classification of dental caries pat-
terns in the primary dentition: a multidi-
mensional scaling analysis. Community
Dent Oral Epidemiol 2003;31:231–238.
Rethman J: Trends in preventive care: caries risk
assessment and indications for sealants. J
Am Dent Assoc 2000;131:8S–12S.
Ripa LW, Leske GS, Sposato A: The surface-spe-
cific caries pattern of participants in a
school-based fluoride mouthrinsing pro-
gram with implications for the use of seal-
ants. J Public Health Dent 1985;45:90–94.
200.3.152.96 - 11/16/2022 5:08:35 PM
Divaris /Preisser /Slade
Pontificia Universidad
Downloaded by:
Roberts-Thomson KF, Slade GD, Bailie RS, En-
dean C, Simmons B, Leach AJ, Raye I, Morris
PS: A comprehensive approach to health pro-
motion for the reduction of dental caries in
remote Indigenous Australian children: a
clustered randomized controlled trial. Int
Dent J 2010;60:245–249.
Selwitz RH, Ismail AI, Pitts NB: Dental caries.
Lancet 2007;369:51–59.
Seow WK: Clinical diagnosis of enamel defects:
pitfalls and practical guidelines. Int Dent J
1997;47:173–182.
Seow WK, Clifford H, Battistutta D, Morawska
A, Holcombe T: Case-control study of early
childhood caries in Australia. Caries Res
2009;43:25–35.
Shaffer JR, Wang X, Desensi RS, Wendell S, Wey-
ant RJ, Cuenco KT, Crout R, McNeil DW,
Marazita ML: Genetic susceptibility to den-
tal caries on pit and fissure and smooth sur-
faces. Caries Res 2012;46:38–46.
Surface-Specific Efficacy of Fluoride
Varnish
Slade GD, Bailie RS, Roberts-Thomson K, Leach
AJ, Raye I, Endean C, Simmons B, Morris P:
Effect of health promotion and fluoride var-
nish on dental caries among Australian Ab-
original children: results from a community-
randomized controlled trial. Community
Dent Oral Epidemiol 2011;39:29–43.
Slade GD, Caplan DJ: Impact of analytic conven-
tions on outcome measures in two longitudi-
nal studies of dental caries. Community
Dent Oral Epidemiol 2000;28:202–210.
Slayton RL, Warren JJ, Kanellis MJ, Levy SM, Is-
lam M: Prevalence of enamel hypoplasia and
isolated opacities in the primary dentition.
Pediatr Dent 2001;23:32–36.
Targino A, Rosenblatt A, Oliveira A, Chaves A,
Santos V: The relationship of enamel defects
and caries: a cohort study. Oral Dis 2011;17:
420–426.
Caries Res 2013;47:78–87
ten Cate JM: Current concepts on the theories of
the mechanism of action of fluoride. Acta
Odontol Scand 1999;57:325–329.
Tewari A, Chawla HS, Utreja A: Comparative
evaluation of the role of NaF, APF and Du-
raphat topical fluoride applications in the
prevention of dental caries – a 2 1/2 years
study. J Indian Soc Pedod Prev Dent 1991; 8:
28–35.
Velló MA, Martínez-Costa C, Catalá M, Fons J,
Brines J, Guijarro-Martínez R: Prenatal and
neonatal risk factors for the development of
enamel defects in low birth weight children.
Oral Dis 2010;16:257–262.
Weintraub JA, Ramos-Gomez F, Jue B, Shain
S, Hoover CI, Featherstone JD, Gansky SA:
Fluoride varnish efficacy in preventing early
childhood caries. J Dent Res 2006; 85: 172–
176.
200.3.152.96 - 11/16/2022 5:08:35 PM
87
Pontificia Universidad
Downloaded by: