Intervention Review

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Fluoride varnishes for preventing dental caries in children and adolescents

  1. Valeria CC Marinho1,
  2. Helen V Worthington2,*,
  3. Tanya Walsh3,
  4. Jan E Clarkson4

Editorial Group: Cochrane Oral Health Group

Published Online: 11 JUL 2013

Assessed as up-to-date: 13 MAY 2013

DOI: 10.1002/14651858.CD002279.pub2

How to Cite

Marinho VCC, Worthington HV, Walsh T, Clarkson JE. Fluoride varnishes for preventing dental caries in children and adolescents. Cochrane Database of Systematic Reviews 2013, Issue 7. Art. No.: CD002279. DOI: 10.1002/14651858.CD002279.pub2.

Author Information

  1. 1

    Queen Mary University of London, Clinical and Diagnostic Oral Sciences, Barts and The London School of Medicine and Dentistry, London, UK

  2. 2

    School of Dentistry, The University of Manchester, Cochrane Oral Health Group, Manchester, UK

  3. 3

    School of Dentistry, The University of Manchester, Manchester, UK

  4. 4

    University of Dundee, Dental Health Services Research Unit, Dundee, Scotland, UK

*Helen V Worthington, Cochrane Oral Health Group, School of Dentistry, The University of Manchester, Coupland III Building, Oxford Road, Manchester, M13 9PL, UK. helen.worthington@manchester.ac.uk.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 11 JUL 2013

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Summary of findings    [Explanations]

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms

 
Summary of findings for the main comparison.

Fluoride varnish compared with placebo/no treatment for preventing caries in children and adolescents

Patient or population: Children and adolescents

Settings: School/clinic

Intervention: Fluoride varnish

Comparison: No treatment/placebo

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of participants
(trials)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

No treatment/placeboFluoride varnish

Permanent tooth surfaces

D(M)FS increment PF - nearest to 3 years (14 trials)

The duration of the trials ranged from 1 to 5 years with most trials (10) being of 2 to 3 years duration
Mean increment in control group 0.171The corresponding mean increments in the intervention group is 0.10 (95% CI 0.07 to 0.12)PF = 0.43 (95% CI 0.30 to 0.57)6478
(13)
⊕⊕⊕⊝
moderate2

Mean increment in control group 2.37The corresponding mean increments in the intervention group is 1.35 (95% CI 1.02 to 1.70)PF = 0.43 (95% CI 0.30 to 0.57)6478
(13)
⊕⊕⊕⊝
moderate2

Mean increment in control group 7.72The corresponding mean increments in the intervention group is 4.40 (95% CI 3.32 to 5.40)PF = 0.43 (95% CI 0.30 to 0.57)6478
(13)
⊕⊕⊕⊝
moderate2

Deciduous tooth surfaces

d((e)/m)fs increment PF - nearest to 3 years (10 trials)

The duration of the trials ranged from 1 to 2.5 years with most trials (7) being of 2 years duration
Mean increment in control group 0.893The corresponding mean increments in the intervention group is 0.56 (95% CI 0.44 to 0.68)PF = 0.37 (95% CI 0.24 to 0.51)3804

(10 )
⊕⊕⊕⊝
moderate4

Mean increment in control group 1.65The corresponding mean increments in the intervention group is 1.04 (95% CI 0.81 to 1.25)PF = 0.37 (95% CI 0.24 to 0.51)3804

(10 )
⊕⊕⊕⊝
moderate4

Mean increment in control group 13.8The corresponding mean increments in the intervention group is 8.69 (95% CI 6.76 to 10.49)PF = 0.37 (95% CI 0.24 to 0.51)3804

(10 )
⊕⊕⊕⊝
moderate4

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI)
CI: confidence interval; PF: prevented fraction

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate
Very low quality: We are very uncertain about the estimate

 1 The mean increments in the control group ranged from 0.17 to 7.72, median 2.37
2 The quality of the evidence was downgraded due to considerable heterogeneity; 9 trials were at high and 4 trials at unclear risk of bias. However this body of evidence showed a consistent, large clinically important effect and we have upgraded the quality of evidence to moderate
3 The mean increments in the control group ranged from 0.89 to 13.8, median 1.65
4 The quality of the evidence was downgraded due to considerable heterogeneity; 5 trials were at high and 5 trials at unclear risk of bias. However this body of evidence showed a consistent, large clinically important effect and we have upgraded the quality of evidence to moderate

 

Background

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms
 

Description of the condition

Dental caries is a highly prevalent chronic disease afflicting a significant proportion of the world population, including around 60% to 90% of school-aged children and the vast majority of adults (Petersen 2004). In general, dental caries levels vary considerably between and within different countries, but children in the lower socio-economic status (SES) groups have higher caries levels than those in the upper SES groups (Chen 1995; Reisine 2001). Untreated caries causes progressive destruction of the crowns of the teeth, often accompanied by severe pain and suffering. The repair and replacement of carious teeth is excessively time consuming and costly, representing a major drain of resources for healthcare systems.

 

Description of the intervention

Professionally-applied fluoride varnishes, developed in the 1960s as a preventive intervention for dental caries, have been extensively used in Europe, Scandinavia and Canada and their use in other countries seems to be increasing, including the United States, where they can be used off-label as caries preventive agents (Bawden 1998; Beltrán-Aguilar 2000; Kallestal 1999; WHO 1994). The use of fluoride varnishes is considered appropriate for at risk tooth surfaces in caries susceptible individuals and for moderate and high caries prevalence child populations in community-based preventive programmes (Petersson 1997). Varnishes were originally developed to prolong the contact time between fluoride and dental enamel, as they adhere to the tooth surface for longer periods (12 hours or more) in a thin layer, and prevent the immediate loss of fluoride after application, thus acting as slow-releasing reservoirs of fluoride making acute toxicity unlikely (Ogaard 1994). Although various different formulations of fluoride varnishes are available, there are two main preparations commercially known as Duraphat and Fluor Protector. Duraphat contains 5% sodium fluoride (NaF), or 22,600 parts per million fluoride ions (ppm F), in a natural resin carrier with some alcohol included as a solvent. Fluor Protector contains 0.9% difluorosilane by weight (1000 ppm F) in polyurethane-based varnish and sets to a thin transparent film (originally developed in 1975 by Arends and Schuthof with a fluoride concentration of 0.7%, the fluoride concentration was changed to 0.1% in 1987). Varnishes are usually applied with small brushes, syringes, or cotton pellets, with or without prior dental prophylaxis, at the frequency of two to four times a year. They are considered safe, despite the high fluoride concentration (in Duraphat for example), because the amount of varnish usually applied to treat one child is only 0.5 ml on average (Petersson 1993; Ripa 1990), which delivers 3 to 11 mg of fluoride ion per dose. This is far below the probable toxic dose of 5 mg/kg body weight (Whitford 1992), even with the potential exposure (ingestion) varying from 3.5 to 11.3 mg of fluoride ion (Johnston 1994).

Numerous clinical trials evaluating the caries preventive effect of fluoride varnishes in children in both permanent and primary teeth have been reported, and these have been the subject of several narrative reviews (Beltrán-Aguilar 2000; Clark 1982; De Bruyn 1987; Petersson 1993; Petersson 1997; Primosch 1985; Seppa 1991; Yanover 1982) and of systematic reviews and meta-analyses (Bader 2004; Carvalho 2010; Clark 1985; Helfenstein 1994; Petersson 2004; Rozier 2001; Strohmenger 2001). It is evident from these reviews and meta-analyses that fluoride varnishes are caries-inhibitory agents. However, they either failed to fully report the quantitative approaches used for data synthesis, or did not include a comprehensive search for individual trials or a formal evaluation of the risk of bias in included trials, despite obvious drawbacks in study design and methods in the trials. Some reviews included trials, mainly carried out in the 1970s, that had adopted the 'split-mouth' design for example (i.e. used half-mouth controls). There is a general agreement against the use of the within-subject paired design for fluoride varnish trials in the literature; a major drawback is that the possibility of significant contamination of control sites cannot be excluded, regardless of the adhesiveness of the material to the tooth surface in the first hours after application (Clark 1982; De Bruyn 1987; Petersson 1993).

 

How the intervention might work

The most important anti-caries effect of fluoride is considered to result from its local action on the tooth/plaque interface, through promotion of remineralisation of early caries lesions and by reducing tooth enamel solubility (Featherstone 1988). Enamel demineralisation is markedly inhibited if fluoride is present at the time of the acid challenge because fluoride diffuses with the acid from plaque into the enamel and acts at the crystal surface to reduce mineral loss. When the pH rises following demineralisation, fluoride can combine with dissolved calcium and phosphate ions to precipitate or grow fluorapatite-like crystalline material within the tooth. Fluoride enhances this mineral gain and provides a material which is more resistant to subsequent acid attack (ten Cate 1999). This occurs with all forms and concentrations of topical fluoride although to a variable extent. Regular use of fluoride toothpaste or mouthrinse results in sustained elevated fluoride concentrations in the oral fluids during the demineralisation/remineralisation cycle, but with higher concentration topical fluoride vehicles (such as varnishes and gels), calcium fluoride is precipitated on the enamel surface and in the plaque. This calcium fluoride acts as a fluoride reservoir which is released when the oral pH falls (Horowitz 1996; Ogaard 1994).

Thus, varnishes deliver fluoride to the surface of enamel and to subsurface carious lesions, where it forms deposits of calcium fluoride and provides a reservoir of fluoride ions (Ogaard 1994). The greatest release occurs during the first three weeks after application, with more gradual release thereafter (Shen 2002).

 

Why it is important to do this review

The prevention of dental caries in children and adolescents is generally regarded as a priority for dental services and considered more cost-effective than its treatment (Burt 1998). Fluoride therapy has been the centrepiece of caries-preventive strategies since the introduction of water fluoridation schemes over five decades ago (Murray 1991). These were introduced when caries was highly prevalent and severe, and when even modest prevention activities led to considerable reductions in disease levels. In the last 30 years, with the substantial decline in dental caries rates in many western countries, an increase in dental fluorosis levels in some countries, and intensive research on the mechanism of action of fluoride highlighting the primary importance of its topical effect, greater attention has been paid to the appropriate use of other fluoride-based interventions (Featherstone 1988; Featherstone 1999; Glass 1982; Marthaler 1996; O'Mullane 1994; Ripa 1991).

The use of topically-applied fluoride products in particular, which are much more concentrated than the fluoride in drinking water, has increased over recent decades. By definition, the term 'topically-applied fluoride' is used to describe those delivery systems which provide fluoride to exposed surfaces of the dentition, at elevated concentrations, for a local protective effect, and are therefore not intended for ingestion. Fluoride-containing toothpastes (dentifrices), mouthrinses, gels and varnishes are the modalities most commonly used at present, either alone or in combination. Various products are marketed in different countries and a variety of caries preventive programmes based on these have been implemented. Toothpastes are by far the most widespread form of fluoride usage (Murray 1991a; Ripa 1991) and although the reasons for the decline in the prevalence of dental caries in children from different countries has been the subject of much debate (de Liefde 1998; Krasse 1996; Marthaler 1996; Marthaler 2004; Nadanovsky 1995), it has been mainly attributed to the gradual increase in, and regular home use of fluoride in toothpaste (Bratthall 1996; Glass 1982; Marthaler 1994; O'Mullane 1994; Ripa 1991; Rolla 1991).

At the same time, the lower caries prevalence now prevailing in many countries and the widespread availability of fluoride from multiple sources have raised the question of whether topically-applied fluorides are still effective in reducing caries, and safe, mainly in terms of the potential risk of fluorosis (mottled enamel). This is particularly important as nearly all child populations in high-income countries are exposed to some source of fluoride, notably in toothpaste, and adverse effects may be rare (such as acute fluoride toxicity) or more subtle (such as mild dental fluorosis) (Marthaler 2004; Murray 1991a).

The evidence on the effect of topically-applied fluoride products on the prevention of dental caries in children has been extensively reviewed in traditional narrative reviews. A number of reviews focusing on the evaluation of specific fluoride active agents within specific delivery systems have used a quantitative meta-analytical approach to synthesise trials results (Ammari 2003; Bartizek 2001; Chaves 2002; Clark 1985; Helfenstein 1994; Johnson 1993; Petersson 2004; Stamm 1984; Stamm 1995; Steiner 2004; Strohmenger 2001; Twetman 2004; van Rijkom 1998). However, there has been no systematic investigation evaluating and comparing the effects of the main modalities of topically-applied fluoride and examining formally the main factors that may influence their effectiveness.

This review is one in a series of systematic reviews of topical fluoride interventions and assesses the effectiveness of fluoride varnishes for the prevention of dental caries in children. It is an update of the review first published in 2002, which suggested a substantial caries-inhibiting effect of fluoride varnish in both the permanent and primary teeth of children, but based largely on a small number of relatively old trials of variable methodological quality (Marinho 2002).

 

Objectives

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms

(1) To determine the effectiveness and safety of fluoride varnishes in preventing dental caries in the child/adolescent population.
(2) To examine whether the effect of fluoride varnishes is influenced by the initial level of caries severity.
(3) To examine whether the effect of fluoride varnishes is influenced by the background exposure to fluoride in water (or salt), toothpastes, or reported fluoride sources other than the study option(s).
(4) To examine whether the effect of fluoride varnishes is influenced by fluoride concentration or application features, such as frequency of use and prophylaxis.

 

Methods

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms
 

Criteria for considering studies for this review

 

Types of studies

Randomised or quasi-randomised controlled trials using or indicating blind outcome assessment, in which fluoride varnish is compared concurrently to a placebo or no treatment group during at least one year.
We excluded randomised or quasi-randomised controlled trials using within-group paired comparison designs (e.g. split-mouth trials), or with open outcome assessment or no indication of blind outcome assessment, or lasting less than one year, or controlled trials where random or quasi-random allocation was not used or indicated.

 

Types of participants

Children or adolescents aged 16 or less at the start of the study (irrespective of initial level of dental caries, background exposure to fluorides, dental treatment level, nationality, setting where intervention is received or time when it started).
Studies where participants were selected on the basis of special (general or oral) health conditions were excluded.

 

Types of interventions

Topical fluoride in the form of varnishes only, using any fluoride agent, at any concentration (ppm F), amount or duration of application, and with any technique of application, prior or post-application. However, frequency of application should have been at least once a year. The control group is placebo or no treatment resulting in the following comparison: Fluoride varnish compared with a placebo or no treatment.

Studies where the intervention consisted of any other caries preventive agent or procedure (e.g. other fluoride-based measures, chlorhexidine, sealants, oral hygiene interventions, xylitol chewing gums) used in addition to fluoride varnish were excluded.

 

Types of outcome measures

The primary outcome measure in this review was caries increment, as measured by change from baseline in the number of decayed, (missing) and filled permanent surfaces / number of decayed, (extracted/missing) and filled primary surfaces (D(M)FS / d(e/m)fs). Caries is defined here as being recorded at the dentine level of diagnosis. If caries data only reported caries at both dentine and enamel lesions combined then this was used in the analysis (see Data collection and analysis for the different ways of recording caries and reporting the D(M)FT/S / d(m)ft/s scores in permanent and primary teeth in clinical trials of caries preventive interventions).

The following outcomes were considered relevant: coronal dental caries and dental fillings, in both the permanent and the primary dentitions, tooth loss, dental pain, specific adverse effects (oral allergic reactions, mucosal irritation, adverse symptoms such as nausea, gagging, vomiting), use of health service resources (such as visits to dental care units, length of dental treatment time).
Studies reporting no dental caries data, reporting only on plaque/gingivitis, calculus, dentine hypersensitivity or fluoride physiological outcome measures (fluoride uptake by enamel or dentine, salivary secretion levels, etc.) were excluded.

 

Search methods for identification of studies

For the identification of trials included or considered for this review, we developed detailed search strategies for each database searched. These were based on the search strategy developed for MEDLINE (OVID) but revised appropriately for each database. The search strategy used a combination of controlled vocabulary and free text terms and was linked with the Cochrane Highly Sensitive Search Strategy (CHSSS) for identifying randomised trials (RCTs) in MEDLINE: sensitivity maximising version (2008 revision) as referenced in chapter 6.4.11.1 and detailed in box 6.4.c of the Cochrane Handbook for Systematic Reviews of Interventions version 5.1.0 (updated March 2011) (Higgins 2011). Details of the current MEDLINE search strategy are provided in Appendix 3. The search of EMBASE was linked to the Cochrane Oral Health Group filter for identifying RCTs, and the searches of LILACS and BBO were linked to the Brazilian Cochrane Center filter.

 

Electronic searching (databases and registers)

We searched the following electronic databases:

  • The Cochrane Oral Health Group's Trials Register (to 13 May 2013) (Appendix 1)
  • The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 4) (Appendix 2)
  • MEDLINE via OVID (1946 to 13 May 2013) (Appendix 3)
  • EMBASE via OVID (1980 to 13 May 2013) (Appendix 4)
  • CINAHL via EBSCO (1980 to 13 May 2013) (Appendix 5)
  • LILACs via BIREME Virtual Health Library (1980 to 13 May 2013) (Appendix 6)
  • BBO via BIREME Virtual Health Library (1980 to 13 May 2013) (Appendix 6)
  • ProQuest Dissertations and Theses (1861 to 13 May 2013) (Appendix 7)
  • Web of Science Conference Proceedings (1945 to 13 May 2013) (Appendix 8).

No restrictions were placed on language or date of publication in the search of the electronic databases.

 

Ongoing trials

A search of the National Institutes of Health registry and results service (ClinicalTrials.gov) was undertaken on 13 May 2013 (Appendix 9).

 

Reference searching

All eligible trial reports, previous meta-analyses and review articles were scanned for relevant references. For the original version of this review reference lists of relevant chapters from preventive dentistry text books on topically-applied fluoride interventions had also been consulted.

 

Handsearching

Some handsearching was carried out for the original version of this review, on journals identified as having the highest yield of eligible RCTs / controlled clinical trials (CCTs):

  • Community Dentistry and Oral Epidemiology (1990 to 1999)
  • British Dental Journal (1999 to 2000)
  • Caries Research (1999 to 2000)
  • Community Dentistry and Oral Epidemiology (1999 to 2000)
  • Journal of the American Dental Association (1999 to 2000)
  • Journal of Dental Research (1999 to 2000)
  • Journal of Public Health Dentistry (1999 to 2000)
  • European Journal of Oral Sciences (1999 to 2000).

For the update of this review, only handsearching done as part of the Cochrane Worldwide Handsearching Programme was carried out. See the Cochrane Masterlist of journals and issues searched to date for more information.

 

Personal contact/correspondence

For the original review, we contacted experts in the field of preventive dentistry to identify any unpublished trials or trials which may not be indexed by the major databases. A letter was sent to the author(s) of each included study published during the 1980s and 1990s in order to obtain information on possible unpublished trials eligible for inclusion. All the authors of trials who had been contacted in order to clarify reported information to enable assessment of eligibility or obtain missing data were also asked for unpublished trials.

Based on information extracted mainly from included trials, a list of manufacturers of fluoride varnishes was created for locating unpublished trials, and three fluoride varnish manufacturers were contacted in October 2000 and in December 2012. Information on any unpublished trials was requested from Colgate Oral Pharmaceuticals, Ivoclar North America and Pharmascience.

 

Data collection and analysis

 

Selection of studies

The screening for eligibility was done in duplicate by at least two review authors for all potential studies identified from all searches performed.

Trial reports thought to be potentially relevant in languages not known by the review authors were translated and the initial form completed by an author with reference to the translator. Attempts were made to contact authors of trials that could not be classified in order to ascertain whether inclusion criteria were met.

 

Data extraction and management

At least two review authors extracted data from all included studies in duplicate. Numerical data presented only in graphs and figures were extracted whenever possible. Attempts were made to contact authors through an open-ended request in order to obtain missing information or for clarification whenever necessary.

Information related to study methodology that was extracted included: study duration (years of follow-up); comparability of baseline characteristics - methods used pre-randomisation in sizing/balancing (stratification based on relevant variables) or used post-randomisation in analysing/adjusting for possible differences in prognostic factors between groups; objectivity/reliability of primary outcome measurement (diagnostic methods and thresholds/definitions used and included, and monitoring of diagnostic errors); and any co-intervention or contamination or both. Information on sponsoring institutions and manufacturers involved was also recorded.

Characteristics related to participants that were extracted included: age (mean and range) at start; caries severity at start (average DMFS/dmfs, DFS/dfs, or other measure); background exposure to other fluoride sources (toothpaste, water, etc.); year study began; location where study was conducted (country); setting where participants were recruited; and dental treatment level (F/DMF).

Characteristics of the intervention that were extracted included: methods (technique/device) of application, prior and post-application; fluoride active agents and concentrations used; frequency and duration of application; and amount applied. Information on what the fluoride varnish was compared to (no treatment or placebo) was also recorded. These data are described in the Characteristics of included studies table.

Different ways of assessing/reporting caries increment (change from baseline as measured by the decayed-missing-filled (DMF) index) in the trials were recorded separately and/or combined according to the components of the index chosen and units measured (DMFT/S, or DFT/S, or DT/S, or FT/S); types of tooth/surface considered (primary/permanent teeth/surfaces, first molar teeth, approximal surfaces, etc.); state of tooth eruption considered (erupted and/or erupting teeth or surface); diagnostic thresholds used (cavitated/dentine lesions, non-cavitated/incipient lesions); methods of examination adopted (clinical or radiographical or both, other); and approaches to account or not for reversals in caries increment adopted (in a net or observed caries increment respectively). In addition, caries increment data have been recorded at all reported time periods (at various follow-ups).

As we were aware that caries increment could be reported differently in different trials, we developed a set of a priori rules to choose the primary outcome data (D(M)FS) for analysis from each study: DFS data would be chosen over DMFS data, and these would be chosen over DS or FS; data for 'all surface types combined' would be chosen over data for 'specific types' only; data for 'all erupted and erupting teeth combined' would be chosen over data for 'erupted' only, and these over data for 'erupting' only; data from 'clinical and radiological examinations combined' would be chosen over data from 'clinical' only, and these over 'radiological' only; data for dentinal/cavitated caries lesions would be chosen over data for enamel/non-cavitated lesions; net caries increment data would be chosen over crude (observed) increment data; and follow-up nearest to three years (often the one at the end of the treatment period) would be chosen over all other lengths of follow-up, unless otherwise stated. When no specification was provided with regard to the methods of examination adopted, diagnostic thresholds used, groups of teeth and types of tooth eruption recorded, and approaches for reversals adopted, the primary choices described above were assumed.

The Characteristics of included studies table provides a description of all the main outcome data reported from each study with the chosen primary outcome measure featuring at the top. All other relevant outcomes identified as being assessed in the trials are also listed in this table.

 

Assessment of risk of bias in included studies

At least two review authors undertook the assessment of the risk of bias in all of the included trials independently. Disagreements were resolved by discussion or the involvement of another review author. This was carried out using The Cochrane Collaboration's tool for assessing risk of bias as outlined in the Cochrane Handbook for Systematic Reviews of Interventions version 5.1 (Higgins 2011), but according to pre-defined criteria which were adapted and refined for the Cochrane topical fluoride reviews updates. Eight domains, namely sequence generation, allocation concealment, blinding of participants, blinding of outcome assessment, incomplete outcome data, selective outcome reporting, baseline balance, and free from contamination or co-intervention, were assessed according to the tool. Each domain included one or more specific entries in a 'Risk of bias' table. Within each entry, information reported in the study was described and a judgement relating to the risk of bias for that entry was assigned. Where the study clearly reported the methodology, a judgement of 'low risk of bias' or ' high risk of bias' was made. Where trial methodology was unclear, a domain was judged at 'unclear risk of bias' unless and until further information became available. After taking into account the additional information provided by the authors of the trials, the overall risk of bias in included trials was assessed over all eight domains. Studies were graded into the following categories.

  • Low risk of bias (plausible bias unlikely to seriously alter the results: all eight domains assessed as at low risk of bias).
  • Moderate risk of bias (plausible bias that raises some doubt about the results: at least one domain assessed as at unclear risk of bias, but none at high risk of bias).
  • High risk of bias (plausible bias that seriously weakens confidence in the results: at least one domain assessed as at high risk of bias).

 

Measures of treatment effect

Prevented fraction (PF) was the measure of treatment effect presented for caries increment. The prevented fraction is calculated as the mean increment in the control group minus the mean increment in the intervention group divided by the mean increment in the control group. For an outcome such as caries increment (where discrete counts are considered to approximate to a continuous scale and are treated as continuous outcome), this measure was considered more appropriate than the mean difference or standardised mean difference since it allowed combination of different ways of measuring caries increment and a meaningful investigation of heterogeneity between trials. It is also simple to interpret.

For outcomes other than caries increment, continuous data were to be analysed according to differences in mean treatment effects and their standard deviations. Dichotomous outcome data were analysed by calculating risk ratios (RRs).

 

Unit of analysis issues

Not all the cluster randomised trials reported results adjusted for the clustering present in the data. In such cases, we estimated the design effect with the intra-class correlation coefficient (ICC) if reported or a value of 0.05 (Lawrence 2008; ICC = 0.045). This was then used to modify the numbers in the intervention and control groups by calculating the effective sample size.

 

Dealing with missing data

We decided that missing standard deviations for caries increments that were not revealed by contacting the original researchers would be imputed through linear regression of log standard deviations on log mean caries increments. This is a suitable approach for caries prevention trials since, as they follow an approximate Poisson distribution, caries increments are closely related (similar) to their standard deviations (van Rijkom 1998). This approach was undertaken wherever possible. Where caries increment data were not reported but baseline and final mean caries scores were reported instead, mean caries increments were calculated and standard deviation of the increments estimated using a correlation coefficient between the baseline and final values of 0.5.

 

Assessment of heterogeneity

Heterogeneity was assessed by inspection of a graphical display of the estimated treatment effects from the trials along with their 95% confidence intervals and by formal tests of homogeneity undertaken prior to each meta-analysis (Thompson 1999). This was also quantified by the I2 statistic and classified according to the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). A rough guide to interpretation: 0% to 40% might not be important, 30% to 60% may represent moderate heterogeneity, 50% to 90% may represent substantial heterogeneity and 75% to 100% considerable heterogeneity.

 

Assessment of reporting biases

Funnel plots (plots of effect estimates versus the inverse of their standard errors (SE)) were drawn where there were sufficient trials (> 10). Asymmetry of the funnel plot may indicate publication bias and other biases related to sample size, though may also represent a true relationship between trial size and effect size. A formal investigation of the degree of asymmetry was planned using the method proposed by Egger 1997 and Harbord 2005.

 

Data synthesis

The meta-analyses were conducted as inverse variance weighted averages. PF variances were estimated using the formula presented in Dubey 1965. Random-effects meta-analyses were performed throughout. The prevented fraction data PF (SE) were entered using the GIV option. Primary and permanent teeth were analysed separately throughout.

Dichotomous outcome data were analysed by calculating RRs. Again random-effects models were used to calculate a pooled estimate of effect.

 

Dealing with studies with more than one intervention arm

In the trials with more than one relevant intervention group and a common control group, such as those comparing different active fluoride agents or concentrations of fluoride ions to a placebo group, summary statistics from the trials (number of children analysed, mean caries increments and standard deviations) from all relevant intervention groups were combined in order to obtain a measure of treatment effect. This enables the inclusion of all relevant data in the primary meta-analysis, although may slightly compromise any secondary investigations of dose response.

 

Subgroup analysis and investigation of heterogeneity

Three potential sources of heterogeneity were specified a priori, and these formed part of the primary objectives of the review. We hypothesised that: (1) the effect of fluoride varnishes differs according to the baseline levels of caries severity, (2) the effect of fluoride varnishes differs according to exposure to other fluoride sources (in water, in toothpastes, etc.) and (3) the effect of fluoride varnishes differs according to characteristics of use (fluoride concentration or application features, such as frequency of use and prophylaxis).

For this update it was also hypothesised that trials could be categorised according to whether the teeth which the intervention had been applied to were within two years of eruption. This is important as newly erupted teeth are thought to be at higher risk of caries. If sufficient number of trials were included, the association of these factors with estimated effects (PF) would be examined by performing random-effects meta-regression analyses in Stata version 12.0 (Stata Corporation, USA) using the program 'Metareg'.

To allow such investigation, relevant data were dealt with as follows: data on 'baseline levels of caries' were calculated from the study sample analysed (final sample) unless otherwise stated, and were averaged among all relevant study groups. Data on 'background exposure to other fluoride sources' combined data on the use of fluoride toothpaste and the consumption of fluoridated water (or salt) and were grouped into two categories: one for trials which were based on samples provided with non-fluoride toothpaste and which were from non-fluoridated areas (non-exposed), and another for trials based on samples using fluoride toothpaste or trials in fluoridated communities or both. When use or non-use of fluoride toothpaste was not clearly indicated in trials carried out in high-income countries, it was assumed that fluoride toothpaste was widely used from the middle of the 1970s (Ripa 1989); this information was sought from authors (or obtained from other sources) when missing from trials carried out in other locations. When data on the year a study had begun were not provided, these were calculated as a 'probable date' by subtracting the duration of the study (in years) plus one extra year, from the publication date of the study.

Further potential sources of heterogeneity were investigated by meta-regression - for different types of control groups (placebo (PL) or no treatment (NT)), different types of randomisation (individual child or cluster) and time since eruption (permanent teeth only), but these post hoc analyses were reported as such, and findings should be treated with caution. It should be remembered that all the meta-regressions have low power and the findings should not be interpreted as no effect.

 

Sensitivity analysis

We intended to undertake a sensitivity analysis including the trials with an overall assessment of low risk of bias, however there were no trials satisfying this criteria. We undertook a sensitivity analysis excluding trials where we imputed missing data such as standard deviations and the design effect in cluster randomised trials.

 

Results

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms
 

Description of studies

 

Results of the search

 

Identification of reports/trials

The full search conducted as described in Search methods for identification of studies on 13 May 2013 has been used to construct the PRISMA flow chart shown in Figure 1.

 FigureFigure 1. Study flow diagram from 2013 search

 

Selection of trials

For this update, 1204 reports were identified by the searches (from databases and other sources) and 104 full-text articles were assessed as potentially eligible. These comprised 40 reports relating to 22 included trials (including the nine trials already identified as included in the initial review), 63 reports relating to 49 excluded trials (including the 33 trials already identified as excluded in the initial review) and one ongoing study which may be eligible (Figure 1).

 

Ongoing trials

We identified one ongoing trial which may be eligible (Macpherson 2012).

 

Included studies

See Characteristics of included studies table for details of each study, a summary of some of the data is given in Additional  Table 1.

There are 22 trials included, published between 1975 and 2012. Six trials were conducted in Sweden (Frostell 1991; Holm 1979; Holm 1984; Koch 1975; Modeer 1984; Sköld 2005), three in Brazil (Arruda 2012; Salazar 2008; Tagliaferro 2011) and China (Chu 2002; Liu 2012; Yang 2008), two in Germany (Borutta 1991; Borutta 2006), Canada (Clark 1985; Lawrence 2008), India (Gugwad 2011; Tewari 1990), UK (Hardman 2007; Milsom 2011), and one in each of the following countries: Spain (Bravo 1997) and USA (Weintraub 2006). Ten trials had multiple publications. Eighteen of the included trials did not mention involvement with a fluoride varnish manufacturer, two acknowledged the supply of varnish (Arruda 2012; Weintraub 2006) and one acknowledged supply of equipment to apply the varnish (Borutta 2006). The only one which acknowledged partial financial support from a fluoride varnish manufacturer (Frostell 1991) also acknowledge support from a sugar company.

Two of the published trials (Hardman 2007; Weintraub 2006) included in this update were listed as ongoing trials in the last published version of this review.

 

Design and methods

All the included trials used parallel group designs (the split-mouth trials were excluded), five being cluster randomised trials (Borutta 2006; Bravo 1997; Hardman 2007; Lawrence 2008; Milsom 2011). Six trials had more than one fluoride varnish treatment group compared to a placebo or no treatment (Borutta 1991; Borutta 2006; Clark 1985; Sköld 2005; Weintraub 2006; Yang 2008). With regard to type of control group used, 14 trials used a no treatment control group, and the remaining eight used a placebo control group, however five of these used an inactive treatment other than varnish ('placebo' solution/distilled water). The study duration (indicated by the total length of follow-up as well as the treatment duration) ranged from one to five years among the included trials (12 of these lasted two years). Studies were of moderate size with seven trials allocating less than 100 children to relevant study groups. The total number of children participating in the 22 included trials (given by the sample analysed at the end of the trial period) was 9595, and ranged from 95 in the smallest trial to 2604 in the largest trial (although this was a cluster trial). Eleven trials conducted the trials in schools or nurseries, eight in clinics and the setting was unclear in the remaining three trials.

 

Participants

The ages of the children at the start of the trials ranged from 1 to 15 years, with similar numbers from both sexes (where these data were reported); 14 trials included participants who were over six years of age at the start, and eight trials included children from one to five (in which primary teeth have been assessed for caries development). Decayed, (missing) and filled permanent surfaces (D(M)FS) at baseline, reported in 11 of the trials, ranged from 0 to 29.2, and from 0 (ds) to 12.4 (dmfs) in the eight trials that reported data for primary dentition. With regard to 'background exposure to other fluoride sources', only three trials were conducted in water fluoridated communities (Holm 1984; Sköld 2005; Weintraub 2006) and only one (Borutta 1991) clearly reported no exposure to fluoride toothpastes; 13 trials reported some other exposure to fluoride (rinses, tablets), with one study mentioning fluoridated milk (Hardman 2007). Seven studies reported that both groups received oral hygiene advice or instruction (Arruda 2012; Chu 2002; Gugwad 2011; Lawrence 2008; Liu 2012; Tagliaferro 2011; Weintraub 2006).

 

Interventions

Teeth were usually painted with a fluoride varnish using a small brush (10 trials), in other trials the use of a probe or cotton swab was reported. The use of NaF-based varnishes (Duraphat, Lawefluor, Bifluorid 12, 3M™ CavityShield™, Fluoridin, Difluorsilane (Fluor Protector) was reported in all trials. The fluoride concentration in 18 trials was 22,600 ppm F; the other trials ranged from 7000 ppm F (Difluorsilane) to 56,300 ppm F (6% NaF + 6% calcium fluoride (CaF) (Borutta 1991)). Two trials had arms with fluoride varnish applied with less than 5% fluoride (Clark 1985; Yang 2008). The application frequency of twice a year was tested in 17 trials and that of four times a year in only three trials (Borutta 1991; Chu 2002; Modeer 1984). One study applied the varnish three times in one week with no other applications (Gugwad 2011). The amount of varnish applied was usually of around 0.5 ml per child (reported in five trials). Where the actual application time was reported it ranged from 1 to 4 minutes. The performance of some form of tooth prophylaxis prior to administering the varnish was reported in seven trials (Clark 1985; Frostell 1991; Gugwad 2011; Holm 1984; Koch 1975; Modeer 1984; Sköld 2005), with four trials with no paste and three with a non-fluoride paste (if with a fluoride paste the trial would have been excluded). The prior tooth cleaning was considered by the review authors as a possible part of the technique of varnish application and not as a separate intervention on its own.

 

Outcome measures

All 22 included trials reported caries increment data at the tooth surface level with D(M)FS reported in 13 trials, 11 trials reporting d(e/m)fs, two trials reporting both D(M)FS and d(e/m)fs (Gugwad 2011; Hardman 2007). Five of the 11 trials reported caries increment data at the tooth level (D(M)FT) and only three trials reported caries increment data for primary teeth at the tooth level (dmft). With regard to the components of the DMFS index used (and types of teeth/surface assessed), 13 trials reported DMFS data (five trials for first molars only and six trials for all tooth surface types) and the other two reported DFS data (one trial for posterior approximal surfaces only and another for first molar fissures only), one also reported DS and FS data separately. (No choice had to be made between DMFS or DFS data in any one trial, but DFS data were chosen over DS/FS data in one of the trials.) All trials reported D(M)FS data on specific teeth or tooth surfaces - first molars, occlusal, mesio-distal (approximal) and/or buco-lingual - but three of these did not report data on all tooth surfaces (whole mouth). D(M)FS data were reported at more than one follow-up time in two trials only; follow-up of two years was the most common among all trials.

Details of all the caries outcomes reported for each trial are given in the Characteristics of included studies table. The caries outcomes used in the meta-analyses are described. Twenty studies included a visual examination, three with the International Caries Detection and Assessment System (ICDAS) (Arruda 2012; Liu 2012; Salazar 2008), three with fibre-optic transillumination (FOTI) (Borutta 2006; Chu 2002; Hardman 2007), and variable use of a probe was reported including tactile criteria. X-rays were used in addition to visual examination in three trials (Frostell 1991; Gugwad 2011; Koch 1975). Two trials diagnosed approximal caries in permanent molars only from X-rays (Modeer 1984; Sköld 2005). Data at the dentine cavitation level of diagnosis were used in the analysis for 16 trials and that for non-cavitated plus cavitated in six trials (Arruda 2012; Gugwad 2011; Lawrence 2008; Sköld 2005; Tewari 1990; Yang 2008;). In seven of the 16 trials with dentine level data, the increment of non-cavitated lesions were also reported (Frostell 1991; Hardman 2007; Holm 1979; Koch 1975; Modeer 1984; Salazar 2008; Tagliaferro 2011). Caries increments on only selected teeth were reported in seven trials: primary anterior teeth (Chu 2002), and permanent molars (Clark 1985; Milsom 2011; Modeer 1984; Sköld 2005; Tagliaferro 2011).

Other dental caries data reported were: caries progression rate (Modeer 1984; Sköld 2005), proportion of children developing new caries (five trials in the permanent dentition, five trials in the primary dentition), proportion of teeth developing new caries and failures (carious teeth) over time (Holm 1984), and 'net' increment data taking account of reversals (Lawrence 2008).

Three studies provided data reporting no adverse effects (Salazar 2008; Sköld 2005; Weintraub 2006). One study reported oral health habits and diet (Arruda 2012) and costs (Bravo 1997).

 

Excluded studies

See Characteristics of excluded studies table for the description of reasons for rejecting each study.

The 49 trials in this section were excluded for a variety of reasons and these have been categorised as related to the study design, intervention/comparison, participant or outcome as given below (some trials appear in more than one category).

 

Study design related

 

Intervention/comparison related

 

Participants related

 

Outcomes related

 

Risk of bias in included studies

 

Allocation

 

Sequence generation

Eight of the included trials (Gugwad 2011; Lawrence 2008; Liu 2012; Milsom 2011; Modeer 1984; Salazar 2008; Tewari 1990; Weintraub 2006) were assessed at low risk of bias for this domain. Six of these used computer generated randomisation sequences, one used the lottery method (Gugwad 2011), and one used random number tables (Modeer 1984). The study by Hardman 2007 was cluster randomised using a computer generated sequence but recruitment into the study was done after randomisation of the clusters and the high rate of pre-recruitment drop-outs (56%) may have led to selection bias so this study was assessed as at unclear risk of bias for this domain. Six trials (Arruda 2012; Bravo 1997; Chu 2002; Frostell 1991; Holm 1979; Tagliaferro 2011) used quasi-random allocation and were assessed at high risk of selection bias. The remaining seven trials provided insufficient information in the study report to enable a judgement to be made and so these were assessed at unclear risk of bias for this domain.

 

Allocation concealment

Allocation was concealed from the investigators in six trials which were assessed at low risk of bias (Gugwad 2011; Hardman 2007; Lawrence 2008; Milsom 2011; Salazar 2008; Weintraub 2006). Six trials reported insufficient information about allocation concealment but the poor randomisation methods used would have made adequate allocation concealment impossible in these trials (Arruda 2012; Bravo 1997; Chu 2002; Frostell 1991; Holm 1979; Tagliaferro 2011) and they were assessed at high risk of bias. In 10 of the included trials there was insufficient information, either in the study report or in response to our emails to study authors, to make a judgement about whether allocation concealment took place so these trials were assessed at unclear risk of bias.

In summary five trials were at low risk of selection bias (Gugwad 2011; Lawrence 2008; Milsom 2011; Salazar 2008; Weintraub 2006), six trials were at high risk of selection bias (Arruda 2012; Bravo 1997; Chu 2002; Frostell 1991; Holm 1979; Tagliaferro 2011) and the remaining 11 trials were at unclear risk of selection bias.

 

Blinding

Five trials were described as double blind and reported the use of a placebo (Arruda 2012; Borutta 1991; Clark 1985; Salazar 2008; Yang 2008), and we assumed that participants were blinded to allocated intervention and assessed these trials at low risk of performance bias. In a further three trials (Chu 2002; Tewari 1990; Weintraub 2006) the use of a placebo was reported and we assessed that participants were likely to be unaware of allocated treatment. These eight trials were assessed at low risk of performance bias. In the study by Gugwad 2011 participant blinding was unclear and this study was assessed at unclear risk of performance bias. In the remaining 13 trials, there was no placebo used and no participant blinding so we assessed these trials at high risk of performance bias.

Blinding of outcome assessors to allocated treatment group was clearly reported in 20 of the 22 included trials (91%) and these were assessed at low risk of detection bias. In two trials (Holm 1984; Lawrence 2008) blind outcome assessment was not reported, but deemed likely, and these were assessed at unclear risk of detection bias.

 

Incomplete outcome data

Seven of the included trials (Holm 1979; Lawrence 2008; Liu 2012; Milsom 2011; Tagliaferro 2011; Tewari 1990; Yang 2008) reported low overall rates of attrition, with numbers lost and reasons similar in each group, so these were assessed at low risk of attrition bias. Two trials (Hardman 2007; Modeer 1984) were assessed at high risk of attrition bias. In Hardman 2007 the overall rate of post-randomisation attrition was high (664 out of 2091) and in Modeer 1984 there was a big difference in percentage of participants lost in each group and the main reason given, poor co-operation, was unbalanced between the groups. The remaining 13 trials were assessed at unclear risk of attrition bias because either the attrition rate was high (Arruda 2012; Salazar 2008), but similar in both groups, or the reasons for attrition were not described (Borutta 2006; Chu 2002; Clark 1985; Gugwad 2011; Holm 1984; Koch 1975; Sköld 2005; Weintraub 2006), the reasons were not balanced between groups (Borutta 1991; Bravo 1997) or the numbers include in the outcome evaluation were not reported (Frostell 1991).

 

Selective reporting

Ideally we would like to compare the outcomes listed in each study protocol with the outcomes reported in the papers but this was seldom possible. Nineteen included trials were assessed at low risk of reporting bias (Borutta 1991; Bravo 1997; Chu 2002; Clark 1985; Frostell 1991; Hardman 2007; Holm 1979; Holm 1984; Koch 1975; Lawrence 2008; Liu 2012; Milsom 2011; Modeer 1984; Salazar 2008; Sköld 2005; Tagliaferro 2011; Tewari 1990; Weintraub 2006; Yang 2008) because the outcomes reported in the results section were all those listed in the methods of the paper. One trial was assessed at high risk of reporting bias (Borutta 2006) and outcomes were reported without estimates of variance. In the remaining two trials (Arruda 2012; Gugwad 2011) the risk of reporting bias was assessed as unclear because one or more measured outcomes were not reported.

 

Other potential sources of bias

 

Baseline imbalance

We also assessed whether there was a balance of important prognostic factors between the arms of the included trials. Eighteen trials (82%) were assessed at low risk of bias for this domain as the differences between groups in prognostic factors such as caries prevalence at baseline and toothbrushing habits or diet or both during the study were not clinically important. However, four trials were assessed at high risk of bias due to baseline imbalance (Arruda 2012; Borutta 2006; Holm 1979; Modeer 1984) for at least one important prognostic factor.

 

Contamination/co-intervention

Thirteen trials (59%) were assessed at low risk of bias due to co-intervention (Arruda 2012; Chu 2002; Gugwad 2011; Hardman 2007; Holm 1984; Koch 1975; Lawrence 2008; Liu 2012; Milsom 2011; Modeer 1984; Tagliaferro 2011; Tewari 1990; Weintraub 2006). In Sköld 2005, 95% of the study participants, including those in the no treatment control group, had at least one fluoride varnish treatment, so this trial was assessed at high risk of bias due to co-intervention. In the remaining seven included trials there were some differences between the groups with regard to co-interventions or contamination but the risk of bias from these was assessed as unclear.

 

Overall risk of bias

A summary of the risk of bias assessments for each domain across studies is shown in Figure 2 and for each study is shown in Figure 3 . None of the trials included in this review are assessed at low risk of bias for all domains. Most (15 trials, 68%) are at high risk of bias in at least one domain (Arruda 2012; Borutta 2006; Bravo 1997; Chu 2002; Frostell 1991; Hardman 2007; Holm 1979; Holm 1984; Koch 1975; Lawrence 2008; Liu 2012; Milsom 2011; Modeer 1984; Sköld 2005; Tagliaferro 2011) and the remaining seven trials are at unclear risk of bias due to the lack of clear information for at least one domain.

 FigureFigure 2. Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included trials
 FigureFigure 3. Risk of bias summary: review authors' judgements about each risk of bias item for each included study

 

Effects of interventions

See:  Summary of findings for the main comparison

The data from 9595 children were included in the pooled meta-analyses, 6478 in the meta-analysis for permanent teeth and 3804 in the meta-analysis for primary teeth (children from two trials were included in both).

 

Effect of fluoride varnish on caries increment

The effects of fluoride varnishes on caries increment were reported in a variety of different ways in the included trials. One study was not able to be included in the meta-analysis because it was a cluster randomised trial with no standard deviations presented (Borutta 2006) and was judged as part of the qualitative data synthesis only (Figure 1). Data from the other trials have been extracted as appropriate to produce pooled estimates as described in the methods section. The results are reported separately for:

(1) Prevented fraction (PF)

  • decayed, (missing) and filled permanent surfaces prevented fraction (D(M)FS PF) ( Analysis 1.1; 13 trials)
  • decayed, (missing) and filled permanent teeth prevented fraction (D(M)FT PF) ( Analysis 1.2; five trials)
  • decayed, (extraction indicated/missing), and filled primary surfaces prevented fraction (d(e/m)fs PF) ( Analysis 1.3; 10 trials) ( Analysis 1.4; one trial)
  • decayed, (extraction indicated/missing), and filled primary teeth prevented fraction (d(e/m)ft PF) ( Analysis 1.5; two trials) ( Analysis 1.6; one trial).

(2) Developing one or more new caries lesions

Imputation of unreported results

  • In the original version of this review, unreported standard deviations (SD) were estimated from an analysis of the 179 available treatment arms for the series of topical fluoride reviews with complete information (as of October 1999). This resulted in a regression equation of: log (SD caries increment) = 0.64 + 0.55* log (mean caries increment), (R2 = 77%). This equation was applied to results of four trials (Clark 1985; Frostell 1991; Holm 1984; Modeer 1984) where the standard deviations were unreported.
  • Two trials (Gugwad 2011; Yang 2008) did not report caries increment data, reporting instead baseline and final mean caries score. Mean caries increments were calculated and standard deviations of the increments estimated using a correlation coefficient between the baseline and final values of 0.5.

Pooling of cluster randomised trials

In order to estimate the PF for the cluster randomised trials we calculated the effective sample size. One cluster randomised trial reported the results not accounting for clustering of the data (Bravo 1997). An intra-class correlation coefficient of 0.05 (using the value reported in a similar trial (Lawrence 2008)) was used to estimate the design effect. This was then used to adjust the sample size of the control and intervention groups. One trial was not able to be included in the meta-analysis because it was a cluster randomised trial with no standard deviations presented (Borutta 2006).

 

Effect on tooth surfaces permanent dentition: D(M)FS prevented fraction

For all 13 trials combined, the D(M)FS prevented fraction pooled estimate was 0.43 (95% confidence interval (CI) 0.30 to 0.57; P < 0.0001), suggesting a substantial benefit from the use of fluoride varnish. The confidence intervals are relatively wide and substantial heterogeneity in the results could be observed graphically (Chi2 = 48.38 on 12 degrees of freedom, P < 0.0001, I2 = 75%) ( Analysis 1.1). The average treatment effect and its confidence interval do not directly provide information on the potential effectiveness of treatment when applied within an individual study setting. A 95% prediction interval was therefore calculated (Riley 2011). This ranged from -0.02 to 0.89, indicative of a benefit of fluoride varnish.

 
Meta-regression and sensitivity analyses: D(M)FS prevented fraction

Meta-regression results for potential effect modifiers specified a priori are given in Additional  Table 2: Random-effects meta-regression analyses of prevented fractions: D(M)FS.

Univariate meta-regression suggested no significant association between estimates of D(M)FS prevented fractions and the pre-specified factors: baseline caries severity, background exposure to fluoridated water, background exposure to fluoride toothpaste, or background exposure to any reported fluoride source, concentration of fluoride, length of follow-up (duration of study), prior prophylaxis or frequency of application. Further univariate meta-regression analyses showed no significant associations between estimates of D(M)FS prevented fractions and time since treated teeth had erupted (<= two years), whether a placebo or no treatment control was used, and whether individual randomisation or cluster randomised design was used.

In order to determine the influence of data imputation and approximation a sensitivity analysis was undertaken, restricting the pooling of trials to those that were fully reported and suitable for analysis (eight trials). The results of this gave rise to greater PF values than the results of the full meta-analysis (PF = 0.55, 95% CI 0.42 to 0.68) and indicator of heterogeneity reduced from I2 = 75% to 62%.

 
Funnel plot: D(M)FS prevented fraction

A funnel plot of the 13 trials in the pooled analysis of D(M)FS prevented fractions indicated no clear asymmetry of prevented fraction and precision. The between-study heterogeneity was large, and as such a formal bias detection tests was not undertaken.

 

Effect on whole teeth permanent dentition: D(M)FT prevented fraction

Five trials reported data which allowed the calculation of the D(M)FT prevented fraction. The pooled estimate of D(M)FT prevented fraction was 0.44 (95% CI 0.11 to 0.76; P = 0.009), suggesting a considerable benefit of fluoride varnish; the confidence intervals are wide, however ( Analysis 1.2). There was, again, substantial heterogeneity between trials (Chi2 = 28.82 on 4 degrees of freedom, P < 0.0001, I2 = 86%).

 

Effect on tooth surfaces primary dentition: d(e/m)fs prevented fraction

Ten trials reported data which allowed the calculation of the d(e/m)fs prevented fraction. The pooled estimate of d(e/m)fs prevented fraction was 0.37 (95% CI 0.24 to 0.51; P < 0.0001), suggesting a substantial benefit of fluoride varnish in the primary dentition ( Analysis 1.3). There was statistically significant heterogeneity between trials (Chi2 = 21.83 on 9 degrees of freedom, P = 0.009, I2 = 59%). A 95% prediction interval for the pooled trials was calculated and ranged from -0.01, 0.76, indicative of a benefit of fluoride varnish in the most part. One trial did not provide data in a format suitable for inclusion in the meta-analysis (Borutta 2006) ( Analysis 1.4).

 
Meta-regression and sensitivity analyses: d(e/m)fs prevented fraction

Meta-regression results for potential effect modifiers specified a priori are reported in Additional  Table 3: Random-effects meta-regression analyses of prevented fractions: d(e/m)fs.

Univariate meta-regression suggested no significant association between estimates of d(e/m)fs prevented fractions and the pre-specified factors: baseline caries severity and background exposure to fluoridated water. The effects of background exposure to fluoride toothpaste and background exposure to any reported fluoride source were inestimable due to collinearity in the data set. Further univariate meta-regression analyses showed no significant association between estimates of d(e/m)fs prevented fractions and concentration of fluoride varnish, length of follow-up (duration of study), frequency of application of varnish, whether a prophylaxis was undertaken prior to application of the varnish, use of a placebo rather than a no treatment control and which study design was used (individual randomisation or cluster randomisation).

In order to determine the influence of data imputation and approximation a sensitivity analysis was undertaken, restricting the pooling of trials to those that were fully reported and suitable for analysis (eight trials). The results of this differed only slightly from the results of the full meta-analysis (PF = 0.45, 95% CI 0.29 to 0.62) and indicator of heterogeneity decreased to 52%.

 
Funnel plot: d(e/m)fs prevented fraction

A funnel plot of the pooled meta-analysis of 10 trials reporting d(e/m)fs prevented fractions indicated no clear relationship between prevented fraction and precision (it appears symmetric). The between-study heterogeneity was large, and as such a formal bias detection test was not undertaken.

 

Effect on whole teeth primary dentition: d(e/m)ft prevented fraction

Two trials reported data which allowed the calculation of the d(e/m)fs prevented fractions. The fixed-effect pooled estimate was 0.65 (95% CI 0.48 to 0.82; P < 0.0001), suggesting a substantial benefit of fluoride varnish in the primary dentition ( Analysis 1.5). There was no evidence of statistically significant heterogeneity between trials (Chi2 = 0.04 on 1 degree of freedom, P = 0.83, I2 = 0%). One study did not provide data in a format suitable for inclusion in the meta-analysis (Borutta 2006) ( Analysis 1.6).

 

Proportion developing new caries

Five trials reported results on the proportion of children developing one or more new caries (whole tooth) in the permanent dentition; five in the primary dentition. There was no evidence of effectiveness of fluoride varnish in the permanent dentition (RR = 0.75, 95% CI 0.53 to 1.05, P = 0.10) ( Analysis 1.7), or the primary dentition (RR = 0.81, 95% CI 0.62 to 1.06, P = 0.13) ( Analysis 1.8). There was substantial heterogeneity in both pooled analyses (Chi2 = 37.18 on 4 degrees of freedom, P < 0.0001, I2 = 89% and Chi2 = 21.68 on 4 degrees of freedom, P = 0.0002, I2 = 82%). However there was a statistically significant difference between the study design subgroups for both analyses, with the individual child randomisation subgroup showing a benefit.

 

Effect of fluoride varnish on other outcomes

Few trials reported data for other relevant outcomes.

 

Discussion

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms
 

Summary of main results

The main question addressed by this review is how effective the use of fluoride varnish for the prevention of caries in children is compared to placebo or no treatment. In this updated review there are now 22 trials published between 1975 and 2012 in which a total of 12,455 children were randomised to treatment with either fluoride varnish or placebo/no treatment. 

The evidence from meta-analysis of the 13 trials assessing the effect of fluoride varnish on the permanent dentition is that the use of fluoride varnish is associated on average with a 43% (95% CI 30% to 57%) reduction in decayed, missing and filled tooth surfaces. The meta-analysis of the 10 trials assessing the effect of fluoride varnish on the primary dentition suggests a 37% (95% CI 24% to 51%) reduction in decayed, missing and filled tooth surfaces. There was considerable statistical heterogeneity in both these estimates.

We explored this heterogeneity in addressing the second, third and fourth objectives of this review which were to examine whether there was any relationship between the caries-preventive effectiveness of fluoride varnish and the initial level of caries severity, background exposure to fluoride (water supply, dentifrice, other fluoride sources), concentration of fluoride, frequency of application and whether prophylaxis was undertaken prior to the application of the varnish. The univariate meta-regressions found no significant associations between any of these pre-specified factors and the estimates of D(M)FS or d(m)fs prevented fractions, despite substantial variations between trials in these factors. As these meta-regression analyses include only a few trials, they have limited power to detect such relationships. However, it is possible that these multiple variations between the included trials is a cause of the substantial heterogeneity associated with both estimates. We also found no significant associations for three factors posed post hoc: time since eruption (for permanent dentition), placebo or no treatment control and study design (individual randomisation versus cluster randomisation).

We performed a sensitivity analysis for the main meta-analysis to take account of the uncertainty we have about the imputations for the missing standard deviations and to take the clustering into account where this had not been done in the cluster randomised trials. The sensitivity analysis showed results with larger effect estimate than the full meta-analysis, with a similar level of heterogeneity.  

 

Overall completeness and applicability of evidence

We found scarce information about the effects of fluoride varnishes on other outcomes such as the proportion of children developing caries or on acceptance of fluoride varnish treatment. Only three studies provided data, reporting no adverse effects. Even though fluoride varnishes are generally considered safe and well accepted, this lack of evidence makes it more difficult for clinicians and policy makers to weigh the benefits of fluoride varnishes in preventing caries against possible shortcomings of the procedure.

In the studies with more than one relevant intervention group and a common control group, such as those comparing different active fluoride agents or concentrations of fluoride ions to a placebo group, summary statistics from the studies (number of children analysed, mean caries increments and standard deviations) from all relevant intervention groups were combined in order to obtain a measure of treatment effect. This enabled the inclusion of all relevant data in the primary meta-analyses, but has limited a secondary investigation of dose-response.

Although we approached the manufacturers of fluoride varnishes requesting additional unpublished trial data, no such data were made available. However, we are aware that at least one additional study has been undertaken, and we have requested the data. If these data are made available to us it will be included in future updates of this review.

This review has evaluated the effects of fluoride varnish alone, versus either placebo or no treatment. We have excluded trials where fluoride varnish plus a complementary intervention, such as toothbrushing or provision of fluoride dentifrice are evaluated. Such trials would answer a different question which may be more relevant to current policy decisions.

The trials included in this review were conducted with participants at a range of caries risk as evidenced by the variability of the caries increments in the control groups. Trials were conducted in a variety of locations with variability in exposure to other sources of fluoride. The prevented fraction appears to be consistent across different populations, levels of caries risk and exposure to other factors. The absolute benefit from fluoride varnish will of course depend on the expected caries increment in the target population. Where expected caries increment is small the absolute benefit of fluoride varnish will be very small.

 

Quality of the evidence

None of the trials included in this review were assessed as at low risk of bias. In fact, 68% were assessed as at high risk of bias, with the remaining at unclear risk. In most of the trials allocation concealment was not reported. As with many long terms trials involving children, there was an average of 19% attrition in the included trials which was not clearly accounted for but is likely to be due to movement of families out of the study area. Overall the quality of the reporting of many of these trials was poor and we were unable to obtain further information from some trials because they were published many years ago.

There is substantial heterogeneity in the body of evidence which addresses the main question of this review. We were unable to find a conclusive explanation for this, but we note that there is substantial variability between the trials in this review with regard to factors which may influence the effect estimate in each study. While we have not been able to demonstrate a significant association between factors such as the initial level of caries severity, background exposure to fluoride (water supply, dentifrice, other fluoride sources), frequency of application, fluoride concentration and whether prophylaxis was undertaken prior to the application of the varnish, neither can we confidently exclude the possibility that one or more of these factors may account for the observed heterogeneity.

 

Potential biases in the review process

A sensitive search strategy was used to identify trials for inclusion in this review and there were no restrictions placed on publication status or language. Many references were translated in order to determine whether or not they reported trials eligible for inclusion in this review.

No clear relationship between prevented fraction and precision could be observed in the funnel plot of the 13 trials (it appeared asymmetric), but as for meta-regression methods, power is limited when the number of trials is small. We cannot eliminate the possibility that bias may have influenced the results of this review.

 

Agreements and disagreements with other studies or reviews

The findings of this updated Cochrane review do not differ from those of the initial review, published first in 2002. The general direction of findings presented is in keeping with those of other reviews (Carvalho 2010; Petersson 2004) which also found evidence for the effectiveness of fluoride varnish. Carvalho 2010 evaluated the effectiveness of fluoride varnish in decreasing dental caries incidence in pre-school children and added two RCTs to the body of evidence assessed in the 2002 version of this review. Azarpazhooh 2008 added four RCTs and three cohort trials to the body of evidence assessed in the previous version of this Cochrane review (Marinho 2002), to produce a body of evidence comprising 13 RCTs and three cohort trials. The review by Azarpazhooh 2008 concluded that there is "clear evidence of the efficacy of fluoride varnish in preventing dental caries in children and adolescents" but in the absence of a meta-analysis, no estimate of the magnitude of the expected benefit was reported, and we are unhappy about the methodological quality of this review. The systematic review by Petersson 2004 based their conclusions on 15 included trials (both RCTs and CCTs) and reported a mean prevented fraction of 30% (0% to 69%) when fluoride varnishes were compared to placebo or no treatment.

This updated Cochrane review includes an additional 13 RCTs compared to the previous version (Marinho 2002). None of the additional included trials is included in the Petersson 2004 review, four are included in the Azarpazhooh 2008 review, and two are included in the Carvalho 2010 review. The large body of evidence contained in this updated Cochrane review provided the best available evidence of the effectiveness of fluoride varnish compared to either placebo or no treatment.

 

Authors' conclusions

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms

 

Implications for practice

This review has found that the application of fluoride varnishes two to four times a year, either in the permanent or primary dentition, is associated with a substantial reduction in caries increment. We found that this relative effect applies in populations with different levels of caries risk and exposure to other sources of fluoride. We also found no evidence that this relative effect was dependent on frequency of varnish application, length of follow-up, whether a prophylaxis was undertaken prior to application of the varnish, concentration of fluoride in the varnish and use of a placebo rather than a no treatment control, although these results should be interpreted with caution. The review does not provide any information on the likelihood of side effects with this treatment and inconclusive information on acceptability.

 
Implications for research

This review of 22 RCTs shows that fluoride varnish, compared to placebo or no treatment, is effective in the prevention of caries in children and adolescents. Despite the large number of trials identified, there is still a paucity of evidence from high quality randomised trials assessing the effectiveness of fluoride varnishes for the prevention of caries in children. It is also important that future trials should include the assessment of other relevant outcomes such as potential side effects (e.g. oral allergic reactions) and those related to acceptability of treatment. The reporting of caries at both the cavitated and non-cavitated level would improve interpretation. Also future trials should consider evaluating the effects of complex interventions incorporating fluoride varnish with other caries preventive strategies, conducted in either the setting of a dental practice or a community site such as a school.

 

Acknowledgements

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms

We would like to acknowledge the considerable amount of work undertaken by Julian Higgins, Stuart Logan and Aubrey Sheiham who were authors on the previous version of this review published in 2002. We would also like to thank the following investigators who provided additional information about their trials: M Bravo (University of Granada), A Borutta (Friedrich-Schiller University), G Davies (Mancunian Community Health NHS Trust), G Frostell (Karolinska Institute), I Mejare (Sweden), A Treide (University of Leipzig), and J Weintraub (University of California). We would also like to thank the help and expertise of the following: R Wents and A Schreiber (German translations), H Pikhart (Russian translations), Chunjie Li (Chinese translations), L Fernandez-Mauleffinch (Portuguese translation) and K Turai (Hungarian and Russian translations); B Anagnostelys, L Jones (Systematic Reviews Training Unit, London), A Littlewood, P Riley and L Fernandez-Mauleffinch (Cochrane Oral Health Group), O Onwood and B Bhandari (QMUL, London). Finally, we would like to thank those who have provided comments and editorial input to this review: S Furness, J Leese and R Floate (Cochrane Oral Health Group), James Bader (University of North Carolina), Elizabeth Treasure (University of Cardiff), Chris Deery (Univeristy of Dundee), Derek Richards (NHS Forth Valley, Stirling), and Iain Pretty (The University of Manchester).

 

Data and analyses

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms
Download statistical data

 
Comparison 1. Fluoride varnish versus placebo/no treatment

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 D(M)FS increment (prevented fraction - nearest to 3 years (13 trials))13Prevented Fraction (Random, 95% CI)0.43 [0.30, 0.57]

 2 D(M)FT increment (prevented fraction - nearest to 3 years (5 trials))5Prevented fraction (Random, 95% CI)0.44 [0.11, 0.76]

 3 d(e/m)fs increment (prevented fraction - nearest to 3 years (10 trials))103804Prevented Fraction (Random, 95% CI)0.37 [0.24, 0.51]

 4 d(e/m)fs increment (prevented fraction - 2 years (incomplete data))Other dataNo numeric data

 5 d(e/m)ft increment (prevented fraction - nearest to 3 years (2 trials))2322Prevented Fraction (Fixed, 95% CI)0.65 [0.48, 0.82]

 6 d(e/m)ft increment (prevented fraction - 2 years (incomplete data))Other dataNo numeric data

 7 Developing one or more new caries (D(M)FT, 5 trials)53253Risk Ratio (M-H, Random, 95% CI)0.75 [0.53, 1.05]

 8 Developing one or more new caries (d(e/m)ft, 5 trials)51228Risk Ratio (M-H, Random, 95% CI)0.81 [0.62, 1.06]

 

Appendices

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms
 

Appendix 1. Cochrane Oral Health Group's Trials Register search strategy

((deminerali* or caries or carious or DMF* or fissure* or decay* or cavit* or "white spot*") AND (fluor* or "PPM F" or "PPMF" or "APF" or "NAF" or "sodium F" or "amine F" or "SNF2" or "stannous F" or acidulat* or "phosphat* fluorid*" or "fluorophosphat* sodium fluorid*" or "amine* fluorid*" or"stannous* fluorid*" or SMFP or "MFP" or monofluor*) AND (varnish* or paint* or laquer* or lacker* or lakk* or coating* or silane* or polyurethane* or duraphat* or "fluor protect*"))

 

Appendix 2. CENTRAL search strategy

#1 MeSH descriptor Tooth demineralization explode all trees 
#2 (carie in All Text or carious in All Text or caries in All Text or DMF* in All Text) 
#3 ( (dental in All Text or tooth in All Text or teeth in All Text or enamel in All Text or dentin* in All Text) and (decay* in All Text or cavit* in All Text or deminerali* in All Text or reminerali* in All Text or "white spot*" in All Text) ) 
#4 (#1 or #2 or #3) 
#5 MeSH descriptor Fluorides explode all trees
#6 (fluoride* in All Text or fluor in All Text or "PPM F" in All Text or PPMF in All Text or APF in All Text or NAF in All Text or "sodium F" in All Text or "amine F" in All Text or SNF2 in All Text or "stannous F" in All Text or "phosphat* f" in All Text or "acidulat* F" in All Text or "acidulat* fluor*" in All Text or "phosphat* fluor*" in All Text or fluorophosphat* in All Text or "amin* fluor*" in All Text or "sodium* fluor*" in All Text or "stannous* fluor*" in All Text or SMFP in All Text or MFP in All Text or monofluor* in All Text)
#7 (#5 or #6) 
#8 (varnish* in All Text or lacquer* in All Text or laquer* in All Text or lacker* in All Text or lakk* in All Text or polyurethane* in All Text)
#9 (#7 and #8)
#10 (duraphat in All Text or "fluor protector" in All Text or "bifluorid 12" in All Text or "cavity shield" in All Text or cavityshield in All Text or duraflor in All Text or Flulak in All Text or "omni varnish" in All Text or "prevident varnish" in All Text or clearshield in All Text or "clear shield" in All Text or allsolutions in All Text)
#11 (#9 or #10)
#12 (#4 and #11)

 

Appendix 3. MEDLINE (OVID) search strategy

1. exp Tooth demineralization/         
2. (carie or caries or carious or DMF$ or ((dental or tooth or teeth or enamel or dentin$) and (decay$ or cavit$ or deminerali$ or reminerali$ or white spot$))).mp.
3. 1 or 2                         
4. exp Fluorides/                                  
5. (fluoride$ or fluor or "PPM F" or PPMF or APF or NAF or "Sodium F" or "Amine F" or SNF2 or "Stannous F" or "phosphat$ F" or "acidulat$ F" or "acidulat$ fluor$" or "phosphat$ fluor$" or fluorphosphat$ or "amin$ fluor$" or "sodium$ fluor$" or "stannous$ fluor$" or SMFP or MFP or monofluor$).mp.
6. 4 or 5                         
7. (varnish$ or lacquer$ or laquer$ or lacker$ or lakk$ or polyurethane$).mp.
8. 6 and 7                                  
9. (duraphat or "fluor protector" or "bifluorid 12" or "cavity shield" or cavityshield or duraflor or Flulak or "omni varnish" or "prevident varnish" or clearshield or "clear shield" or allsolutions).mp.
10. 8 or 9                         
11. 3 and 10

The above subject search was linked to the Cochrane Highly Sensitive Search Strategy (CHSSS) for identifying randomised trials in MEDLINE: sensitivity maximising version (2008 revision) as referenced in Chapter 6.4.11.1 and detailed in box 6.4.c of theCochrane Handbook for Systematic Reviews of Interventions version 5.1.0 [updated March 2011] (Higgins 2011).

1. randomized controlled trial.pt.
2. controlled clinical trial.pt.
3. randomized.ab.
4. placebo.ab.
5. drug therapy.fs.
6. randomly.ab.
7. trial.ab.
8. groups.ab.
9. or/1-8
10. exp animals/ not humans.sh.
11. 9 not 10

The previous version of this review used the following search strategy for MEDLINE via SILVERPLATTER (search undertaken 2001):

[(CARIE* or (DENT* near CAVIT*) or TOOTH* DECAY* or DMF* or (explode "DENTAL-CARIES"/ ALL SUBHEADINGS))
and ((FLUOR* or explode "FLUORIDES"/ ALL SUBHEADINGS) and ((VARNISH*) or (LACQUER* or LAQUER*) or (VERNIZ*) or (LACKER*) or (LAKK*) or (SILANE* or POLYURETHANE*)) or (DURAPHAT* or FLUOR PROTECTOR*)]

A search was undertaken for the fluoride series of reviews (considering varnish, gels, toothpastes, mouthrinses) in 1997, using the search strategy below for MEDLINE via SILVERPLATTER:

(a) [("DENTAL-CARIES" explode all subheadings or "DENTAL-CARIES-ACTIVITY-TESTS" all subheadings or "DENTAL-CARIES-SUSCEPTIBILITY" all subheadings or CARIE* or DMF*) and (("FLUORIDES" explode all subheadings or "FLUORIDES,-TOPICAL" explode all subheadings or FLUOR* or AMF or AMINE F OR SNF2 OR STANNOUS F OR NAF OR SODIUM F OR APF OR SMFP OR MFP OR MONOFLUOR*) or ("CARIOSTATIC-AGENTS" explode all subheadings or "DENTAL-PROPHYLAXIS" explode all subheadings or "DENTIFRICES" explode all subheadings or "MOUTHWASHES" explode all subheadings or CARIOSTA* or PROPHYLA* or ANTICARI* or ANTI CARI* or VARNISH* or LACQUER* or DURAPHAT or GEL* or TOOTHPASTE* or TOOTH PASTE* or PASTE* or DENTIFRIC* or MOUTHRINS* or MOUTH RINS* or RINS* or MOUTHWASH* or MOUTH WASH*))].
(b) [((explode FLUORIDES/ all subheadings) or (explode FLUORIDES-TOPICAL/ ALL SUBHEADINGS) or (FLUOR*) or (AMF or AMINE F OR SNF2 OR STANNOUS F OR NAF OR SODIUM F OR APF OR MFP OR SMFP OR MONOFLUOR* OR DURAPHAT)) and ((CARI*) or (DMF*) or (TOOTH*) or (TEETH*) or (DENT* in TI, in AB, in MESH)) or ((explode CARIOSTATIC-AGENTS/ all subheadings) or (ANTICARI* or ANTI CARI*) or (explode MOUTHWASHES/ all subheadings) or (MOUTHWASH* or MOUTH WASH*) or (MOUTHRINS* or MOUTH RINS*) or (VARNISH* or LACQUER*))]

 

Appendix 4. EMBASE (OVID) search strategy

1. exp Tooth demineralization/         
2. (carie or caries or carious or DMF$ or ((dental or tooth or teeth or enamel or  dentin$) and (decay$ or cavit$ or deminerali$ or reminerali$ or white spot$))).mp.
3. 1 or 2                         
4. exp Fluorides/                                  
5. (fluoride$ or fluor or "PPM F" or PPMF or APF or NAF or "Sodium F" or "Amine F" or SNF2 or "Stannous F" or "phosphat$ F" or "acidulat$ F" or "acidulat$ fluor$" or "phosphat$ fluor$" or fluorphosphat$ or "amin$ fluor$" or "sodium$ fluor$" or "stannous$ fluor$" or SMFP or MFP or monofluor$).mp.
6. 4 or 5                         
7. (varnish$ or lacquer$ or laquer$ or lacker$ or lakk$ or polyurethane$).mp.
8. 6 and 7                                  
9. (duraphat or "fluor protector" or "bifluorid 12" or "cavity shield" or cavityshield or duraflor or Flulak or "omni varnish" or "prevident varnish" or clearshield or "clear shield" or allsolutions).mp.
10. 8 or 9                         
11. 3 and 10

The above subject search was linked to the Cochrane Oral Health Group filter for EMBASE via OVID:

1. random$.ti,ab.
2. factorial$.ti,ab.
3. (crossover$ or cross over$ or cross-over$).ti,ab.
4. placebo$.ti,ab.
5. (doubl$ adj blind$).ti,ab.
6. (singl$ adj blind$).ti,ab.
7. assign$.ti,ab.
8. allocat$.ti,ab.
9. volunteer$.ti,ab.
10. CROSSOVER PROCEDURE.sh.
11. DOUBLE-BLIND PROCEDURE.sh.
12. RANDOMIZED CONTROLLED TRIAL.sh.
13. SINGLE BLIND PROCEDURE.sh.
14. or/1-13
15. ANIMAL/ or NONHUMAN/ or ANIMAL EXPERIMENT/
16. HUMAN/
17. 16 and 15
18. 15 not 17
19. 14 not 18

 

Appendix 5. CINAHL (EBSCO) search strategy

S1 (MH "Tooth demineralization+") 
S2 (carie or caries or carious or DMF* or cavit* or deminerali* or reminerali* or "white spot"*)          
S3 S1 or S2 
S4 (MH "Fluorides+") 
S5 (fluoride* or fluor or "PPM F" or PPMF or APF or NAF or "Sodium F" or "Amine F" or SNF2 or "Stannous F" or "phosphat* F" or "acidulat* F" or "acidulat* fluor*" or "phosphat* fluor*" or fluorphosphat* or "amin* fluor*" or "sodium* fluor*" or "stannous* fluor*" or SMFP or MFP or monofluor*) 
S6 S4 or S5 
S7 (varnish* or lacquer* or laquer* or lacker* or lakk* or polyurethane*)            
S8 S6 and S7    
S9 (duraphat or "fluor protector" or "bifluorid 12" or "cavity shield" or cavityshield or duraflor or Flulak or "omni varnish" or "prevident varnish" or clearshield or "clear shield" or allsolutions) 
S10 S8 or S9  
S11 S3 and S10 

 

Appendix 6. LILACS/BBO (BIREME) search strategy

((Mh Fluorides or fluoride$ or fluoruro$ or fluoreto$) AND (varnish$ or barniz$ or verniz$ or laquer$ or lacquer or polyurethane)) [Words] and (Mh Dental caries or carie$ or carious) [Words]

The above subject search was linked to the Brazilian Cochrane Center filter for LILACs/BBO via BIREME:

Pt randomized controlled trial OR Pt controlled clinical trial OR Mh randomized controlled trials OR Mh random allocation OR Mh double-blind method OR Mh single-blind method) AND NOT (Ct animal AND NOT (Ct human and Ct animal)) OR (Pt clinical trial OR Ex E05.318.760.535$ OR (Tw clin$ AND (Tw trial$ OR Tw ensa$ OR Tw estud$ OR Tw experim$ OR Tw investiga$)) OR ((Tw singl$ OR Tw simple$ OR Tw doubl$ OR Tw doble$ OR Tw duplo$ OR Tw trebl$ OR Tw trip$) AND (Tw blind$ OR Tw cego$ OR Tw ciego$ OR Tw mask$ OR Tw mascar$)) OR Mh placebos OR Tw placebo$ OR (Tw random$ OR Tw randon$ OR Tw casual$ OR Tw acaso$ OR Tw azar OR Tw aleator$) OR Mh research design) AND NOT (Ct animal AND NOT (Ct human and Ct animal)) OR (Ct comparative study OR Ex E05.337$ OR Mh follow-up trials OR Mh prospective trials OR Tw control$ OR Tw prospectiv$ OR Tw volunt$ OR Tw volunteer$) AND NOT (Ct animal AND NOT (Ct human and Ct animal)))and not (Ct ANIMAL AND NOT (Ct HUMAN and Ct ANIMAL)))

The previous version of this review used the following search strategy for LILACS via BIREME (search undertaken 1999):

[(fluor$ or ppmf or ppm f or amf or snf or naf or apf or mfp or smfp or monofluor$ or duraphat$) and (carie$ or dmf$ or cpo$ or tooth$ or teeth$ or dent$ or dient$ or anticarie$ or cario$ or mouthrins$ or mouth rins$ or rinse$ or bochech$ or enjuag$ or verniz$ or varnish$ or barniz$ or laca$ or gel or gels)] and [random$ or aleatori$ or acaso$ or azar$ or blind$ or mask$ or cego$ or cega$ or ciego$ or ciega$ or placebo$ or(clinic$ and (trial$ or ensaio$ or estud$)) or (control$ and (trial$ or ensaio$ or estud$))]

 

Appendix 7. Proquest Dissertations and Theses search strategy

all(fluoride*) AND all((varnish* OR laquer* or lacquer* or paint*))

 

Appendix 8. Web of Science Conference Proceedings search strategy

# 1  TS=(deminerali* or caries or carious or DMF* or fissure* or decay* or cavit* or "white spot*")
# 2  TS=(varnish* or paint* or laquer* or lacker* or lakk* or coating* or silane* or polyurethane* or duraphat* or "fluor protect*")
# 3  TS=(fluoride* or "PPM F" or "PPMF" or "APF" or "NAF" or "sodium F" or "amine F" or "SNF2" or "stannous F" or acidulat* or "phosphat* fluorid*" or "fluorophosphat* sodium fluorid*" or "amine* fluorid*" or"stannous* fluorid*" or SMFP or "MFP" or monofluor*)
# 4  #1 and #2 and #3

 

Appendix 9. ClinicalTrials.gov search strategy

fluoride* and varnish*

 

What's new

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms

Last assessed as up-to-date: 13 May 2013.


DateEventDescription

18 February 2014AmendedMinor edit to additional reference.



 

History

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms

Protocol first published: Issue 3, 2000
Review first published: Issue 3, 2002


DateEventDescription

9 July 2013New search has been performedSearches updated May 2013.

9 July 2013New citation required but conclusions have not changedReview update completed with 22 included trials (9 in previously published version of the review).
Changes in authorship.

27 August 2008AmendedConverted to new review format.



 

Contributions of authors

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms

Valeria Marinho (VM) has conceived, designed, written and co-ordinated the original review, and the updated review. VM performed extensive work in the original review that was the foundation of the updated review, including all data analysis. For both the original and current versions, VM has designed and undertaken search strategies, screened search results, organised retrieval of papers, screened papers against eligibility criteria, selected studies, extracted data, undertaken risk of bias assessments, entered data into Excel and RevMan, written to authors of trial reports, obtained and provided additional data about reports, provided advice on multiple aspects of the review, including analysis, written and revised the update.

Helen Worthington (HW) contributed to the development of the update, undertook screening of full search, extracted data for the 'Characteristics of included studies' tables, undertook risk of bias, extracted outcome data, undertook analysis including meta-regression, crafted PRISMA flow chart and 'Summary of findings' table, and wrote the update.

Tanya Walsh (TW) undertook screening of full search, extracted data for the 'Characteristics of included studies' tables, undertook risk of bias, extracted outcome data, undertook analysis including meta-regression and prediction intervals, wrote the results section.

Jan Clarkson (JC) contributed to the development of the update, assisted with screening, extracted data for the 'Characteristics of included studies' tables, checked risk of bias and wrote the update.

 

Declarations of interest

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms

Tanya Walsh and Helen Worthington were authors of the report of the Milsom 2011 trial but had no involvement with the risk of bias assessment for this study.

 

Sources of support

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms
 

Internal sources

  • Queen Mary University of London, UK.
  • Department of Epidemiology and Public Health (UCL), UK.
  • Systematic Reviews Training Unit, Institute of Child Health (UCL), UK.
  • Medical Research Council, UK.
  • The University of Manchester, UK.
  • Manchester Academic Health Sciences Centre (MAHSC), UK.
    The Cochrane Oral Health Group is supported by MAHSC and the NIHR Manchester Biomedical Research Centre

 

External sources

  • CAPES - Ministry of Education, Brazil.
  • Cochrane Oral Health Group Global Alliance, UK.
    All reviews in the Cochrane Oral Health Group are supported by Global Alliance member organisations (British Orthodontic Society, UK; British Society of Paediatric Dentistry, UK; Canadian Dental Hygienists Association, Canada; National Center for Dental Hygiene Research & Practice, USA and New York University College of Dentistry, USA) providing funding for the editorial process (http://ohg.cochrane.org/)
  • National Institute for Health Research (NIHR), UK.
    CRG funding acknowledgement:
    The NIHR is the largest single funder of the Cochrane Oral Health Group
    Disclaimer:
    The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the NIHR, NHS or the Department of Health

 

Differences between protocol and review

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms

We have removed mention of school year from the 'Types of studies' section and now require all included studies to have at least a 12-month follow-up.
We have removed 'unacceptability of drop-outs during the trial/post-randomisation exclusions (in non-placebo trials)' as we now do not feel that this can be looked at in this way due to the large numbers of drop-outs in both groups, for other reasons.

* Indicates the major publication for the study

References

References to studies included in this review

  1. Top of page
  2. Abstract
  3. Summary of findings
  4. Background
  5. Objectives
  6. Methods
  7. Results
  8. Discussion
  9. Authors' conclusions
  10. Acknowledgements
  11. Data and analyses
  12. Appendices
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Sources of support
  18. Differences between protocol and review
  19. Characteristics of studies
  20. References to studies included in this review
  21. References to studies excluded from this review
  22. References to ongoing studies
  23. Additional references
  24. References to other published versions of this review
Arruda 2012 {published data only}
Borutta 1991 {published and unpublished data}
  • Borutta A, Kunzel W, Rubsam F. The caries-protective efficacy of 2 fluoride varnishes in a 2-year controlled clinical trial [Kariesprotektive Wirksamkeit zweier Fluoridlacke in einer klinisch kontrollierten Zweijahresstudie]. Deutsche Zahn Mund und Kieferheilkunde Zentralblatt 1991;79:543-9.
Borutta 2006 {published and unpublished data}
  • Borutta A, Hufnagl S, Möbius S, Reuscher G. Caries inhibition of fluoride varnishes among pre-school children: results after one-year. Oralprophylaxe 2006;28(1):8-14.
  • Borutta A, Reuscher G, Hufnagl S, Möbius S. Caries prevention with fluoride varnishes among preschool children [Kariesprophylaxe mit Fluoridlacken bei Vorschulkindern]. Gesundheitswesen 2006;68(11):731-4.
  • Terekhova TN, Borutta A, Shakovets NV, Klenovskaia MI, Minchenia OV. Dependence of caries protective effect of fluoride varnishes applications on first permanent molars in schoolchildren on the intensity of caries of temporary teeth. Stomatologiia 2011;90(6):61-5.
Bravo 1997 {published and unpublished data}
  • Bravo M, Baca P, Llodra JC, Osorio E. A 24-month study comparing sealant and fluoride varnish in caries reduction on different permanent first molar surfaces. Journal of Public Health Dentistry 1997;57:184-6.
  • Bravo M, García Anllo I, Baca P, Llodra JC. A 48-month survival analysis comparing sealant (Delton) with fluoride varnish (Duraphat) in 6- to 8-year-old children. Community Dentistry and Oral Epidemiology 1997;25:247-50.
  • Bravo M, Llodra JC, Baca P, Osorio E. Effectiveness of visible light fissure sealant (Delton) versus fluoride varnish (Duraphat): 24-month clinical trial. Community Dentistry and Oral Epidemiology 1996;24:42-6.
  • Bravo M, Montero J. Effectiveness of visible light fissure sealant (Delton) versus fluoride varnish (Duraphat): a 9-year clinical trial. Journal of Dental Research 2002;81(Spec Iss A):A-185 (Abs No 1347).
  • Bravo M, Montero J, Bravo JJ, Baca P, Llodra JC. Sealant and fluoride varnish in caries: a randomized trial. Journal of Dental Research 2005;84(12):1138-43.
  • Bravo Pérez M, Llodra Calvo JC, Baca García P, Osorio Ruiz E, Junco Lafuente P. Fissure sealants versus fluorine varnish on the first permanent molars: economic assessment [Selladores de fisuras frente a barniz de flúor en primeros molares permanentes: evaluación económica]. Atención Primaria 1995;15(3):143-7.
Chu 2002 {published data only}
  • Chu CH, Lo EC, Lin HC. Effectiveness of silver diamine fluoride and sodium fluoride varnish in arresting dentin caries in Chinese pre-school children. Journal of Dental Research 2002;81:767-70.
  • Lo EC, Chu CH, Lin HC. A community-based caries control program for pre-school children using topical fluorides: 18-month results. Journal of Dental Research 2001;80(12):2071-4.
  • Wong MC, Lam KF, Lo EC. Analysis of multilevel grouped survival data with time-varying regression coefficients. Statistics in Medicine 2011;30(3):250-9.
  • Wong MC, Lam KF, Lo EC. Bayesian analysis of clustered interval-censored data. Journal of Dental Research 2005;84(9):817-21.
Clark 1985 {published data only (unpublished sought but not used)}
  • Clark DC, Stamm JW, Quee TC, Robert G. Results of the Sherbrooke-Lac Megantic fluoride varnish study after 20 months. Community Dentistry and Oral Epidemiology 1985;13:61-4.
  • Clark DC, Stamm JW, Robert G, Tessier C. Results of a 32-month fluoride varnish study in Sherbrooke and Lac- Megantic, Canada. Journal of the American Dental Association 1985;111:949-53.
  • Clark DC, Stamm JW, Tessier C, Robert G. The final results of the Sherbrooke-Lac Megantic fluoride varnish study. Journal of the Canadian Dental Association 1987;53:919-22.
Frostell 1991 {published and unpublished data}
  • Frostell G, Birkhed D, Edwardsson S, Goldberg P, Petersson LG, Priwe C, et al. Effect of partial substitution of invert sugar for sucrose in combination with Duraphat treatment on caries development in preschool children: the Malmö Study. Caries Research 1991;25(4):304-10.
  • Peyron M, Matsson L, Birkhed D. Progression of approximal caries in primary molars and the effect of Duraphat treatment. Scandinavian Journal of Dental Research 1992;100:314-8.
Gugwad 2011 {published and unpublished data}
  • Gugwad SC, Shah P, Lodaya R, Bhat C, Tandon P, Choudhari S, et al. Caries prevention effect of intensive application of sodium fluoride varnish in molars in children between age 6 and 7 years. Journal of Contemporary Dental Practice 2011;12:408-13.
Hardman 2007 {published and unpublished data}
  • Hardman MC, Davies GM, Duxbury JT, Davies RM. A cluster randomised controlled trial to evaluate the effectiveness of fluoride varnish as a public health measure to reduce caries in children. Caries Research 2007;41:371-6.
Holm 1979 {published data only}
Holm 1984 {published and unpublished data}
Koch 1975 {published data only}
Lawrence 2008 {published data only}
  • Lawrence HP, Binguis D, Douglas J, McKeown L, Switzer B, Figueiredo R, et al. A 2-year community-randomized controlled trial of fluoride varnish to prevent early childhood caries in Aboriginal children. Community Dentistry and Oral Epidemiology 2008;36:503-16.
  • Lawrence HP, Binguis D, Switzer B, McKeown L, Figueiredo R, Laporte A, et al. Randomized fluoride varnish trial for preventing ECC in Aboriginal communities. Canadian Journal of Dental Hygiene 2007;41(2):113.
Liu 2012 {published data only}
Milsom 2011 {published data only}
  • Milsom KM, Blinkhorn AS, Walsh T, Worthington HV, Kearney-Mitchell P, Whitehead H, et al. A cluster-randomized controlled trial: fluoride varnish in school children. Journal of Dental Research 2011;90:1306-11.
Modeer 1984 {published and unpublished data}
  • Modeer T, Twetman S, Bergstrand F. Three-year study of the effect of fluoride varnish (Duraphat) on proximal caries progression in teenagers. Scandinavian Journal of Dental Research 1984;92:400-7.
Salazar 2008 {published data only}
  • Salazar M. [Efetividade da aplicação semestral de verniz fluoretado no controle da cárie dentária em pré-escolares: resultados após 12 meses de acompanhamento]. Effectiveness of Bi-Annual Fluoride Varnish Application in the Control of Dental Caries in Preschool Children: Results after 12 Months of Follow-Up [Thesis]. Rio de Janeiro, Brazil: Universidade do Estado do Rio de Janeiro, 2008.
Sköld 2005 {published data only}
  • Sköld U, Petersson LG, Lith A, Birkhed D. Effect of school-based fluoride varnish programmes on approximal caries in adolescents from different caries risk areas. Caries Research 2005;39(4):273-9.
  • Sköld UM. On caries prevalence and school-based fluoride programmes in Swedish adolescents. Swedish Dental Journal. Supplement 2005;(178):11-75.
Tagliaferro 2011 {published and unpublished data}
  • Tagliaferro EP, Pardi V, Ambrosano GM, Meneghim Mde C, da Silva SR, Pereira AC. Occlusal caries prevention in high and low risk schoolchildren. A clinical trial. American Journal of Dentistry 2011;24:109-14.
Tewari 1990 {published data only (unpublished sought but not used)}
  • Tewari A, Chawla HS, Utreja A. Caries preventive effect of three topical fluorides (1 1/2 years clinical trial in Chandigarh school children of North India). Journal of the International Association of Dentistry for Children 1984;15:71-81.
  • Tewari A, Chawla HS, Utreja A. Comparative evaluation of the role of NaF, APF & Duraphat topical fluoride applications in the prevention of dental caries--a 2 1/2 years study. Journal of the Indian Society of Pedodontics and Preventative Dentistry 1990;8:28-35.
Weintraub 2006 {published and unpublished data}
  • Eakle WS, Featherstone JD, Weintraub JA, Shain SG, Gansky SA. Salivary fluoride levels following application of fluoride varnish or fluoride rinse. Community Dentistry and Oral Epidemiology 2004;32(6):462-9.
  • Weintraub JA, Ramos-Gomez F, Jue B, Shain S, Hoover CI, Featherstone JD, et al. Fluoride varnish efficacy in preventing early childhood caries. Journal of Dental Research 2006;85(2):172-6.
Yang 2008 {published data only}
  • Yang G, Lin JH, Wang JH, Jiang L. Evaluation of the clinical effect of fluoride varnish in preventing caries of primary teeth. West China Journal of Stomatology 2008;26(2):159-61.

References to studies excluded from this review

  1. Top of page
  2. Abstract
  3. Summary of findings
  4. Background
  5. Objectives
  6. Methods
  7. Results
  8. Discussion
  9. Authors' conclusions
  10. Acknowledgements
  11. Data and analyses
  12. Appendices
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Sources of support
  18. Differences between protocol and review
  19. Characteristics of studies
  20. References to studies included in this review
  21. References to studies excluded from this review
  22. References to ongoing studies
  23. Additional references
  24. References to other published versions of this review
Alves 1997 {published data only}
  • Alves AC, Medeiros UV. Fluoride varnish: Therapeutic effect in children of high caries risk. Journal of Dental Research 1997;76(5):951 (Abs No 6).
Autio-Gold 2001 {published data only}
  • Autio J, Courts F. Effect of fluoride varnish on caries progression. Journal of Dental Research 2000;79(Spec Iss 1):210 (Abs No 532).
  • Autio-Gold JT. Caries Prevention in High-Risk Preschool Children in the United States [Thesis]. Oulu, Finland: Oulu University Press, 2005.
  • Autio-Gold JT, Courts F. Assessing the effect of fluoride varnish on early enamel carious lesions in the primary dentition. Journal of the American Dental Association 2001;132:1247-53.
Billy-Pryga 1983 {published data only}
  • Billy-Pryga Z, Zakrzewka-Pysz E, Ilewicz L. [Klinische untersuchung der schutzwirkung des Fluor-Protector-Lackes in der kariesprophylaxe]. Dental Revue 1980;10:16-8.
  • Billy-Pryga Z, Zakrzewska-Pysz E. Clinical evaluation of Duraphat and Fluor-Protector preparations in caries prevention [Ocena kliniczna preparatow Duraphat i Fluor-Protector w profilaktyce prochnicowej]. Czasopismo Stomatologiczne 1983;36(2):109-15.
Bodnar 1984 {published data only}
  • Bodnar Z, Tarjan I, Keri I. Clinical experience with the use of Duraphat lacquer [A "Duraphat" lakk alkalmazasaval kapcsolatos klinikai tapasztalatok]. Fogorvosi Szenile 1984;77:279-82.
Demito 2011 {published data only}
  • Demito CF, Rodrigues GV, Ramos AL, Bowman SJ. Efficacy of a fluoride varnish in preventing white-spot lesions as measured with laser fluorescence. Journal of Clinical Orthodontics 2011;45(1):25-9.
Dülgergil 2005 {published data only}
  • Dülgergil CT, Ercan E, Yildirim I. A combined application of ART-fluoride varnish for immigrant junior field-workers: 12-months follow-up field trial in rural Anatolia. Oral Health & Preventive Dentistry 2005;3:97-104.
Grodzka 1982 {published and unpublished data}
Hetzer 1973 {published data only}
  • Hetzer G, Irmisch B. Caries prevention using fluoride varnish (Duraphat)--clinical results and experiences [Kariesprotektion durch Fluorlack (Duraphat)--Klinische Ergebnisse und Erfahrungen]. Deutsche Stomatologie 1973;23:917-22.
Heuser 1968 {published data only}
  • Heuser H, Schmidt HF. Dental caries prophylaxis by deep impregnation of the dental enamel with fluorine lac [Zahnkariesprophylaxe durch Tiefenimpragnierung des Zahnschmelzes mit Fluor-Lack]. Stoma Heidelb 1968;21:91-100.
  • Schmidt H. Caries prevention by means of deep impregnation of the dental enamel with fluoride lacquer. Deutsche Stomatologie 1971;21:139-42.
Hochstein 1975 {published data only}
  • Hochstein HJ, Hochstein U, Breitung L. Experience with the fluoride lacker Duraphat [Erfahrungen mit dem Fluorlack Duraphat]. ZWR 1975;84:26-30.
Ivanova 1990 {published data only (unpublished sought but not used)}
  • Ivanova EN. The comparative efficacy of local anticaries agents [Sravnitel'naia effektivnost' mestnykh protivokarioznykh sredtsv]. Stomatologiia Mosk 1990;69:60-1.
Ji 2007 {published data only (unpublished sought but not used)}
  • Ji PH, Xu QL, Ba Y. Clinical evaluation of fluor protector and glass-ionomer cement used as pit and fissure sealant for preventing pit and fissure caries in children. Shanghai Kou Qiang Yi Xue 2007;16:374-6.
Kolehmainen 1979 {published data only}
  • Kolehmainen L, Kerosuo E. The clinical effect of application of a urethane lacquer containing silane fluorine. A one-year study. Proceedings of the Finnish Dental Society 1979;75:69-71.
Kolehmainen 1981 {published data only}
Kunin 1991 {published data only}
  • Kunin AA, Kharin OV. The use of a fluoride varnish and helium-neon laser light in preventing caries of the primary teeth [Ispol'zovanie ftoristogo laka i sveta gelii-neonovogo lazera v profilaktike kariesa vremennykh zubov]. Stomatologiia Mosk 1991;(4):71-2.
Lagutina 1978 {published data only}
  • Lagutina NJ, Vorobjev VS, Grabetskij AA, Stepanov AV. Clinical evaluation of home fluoride-containing varnish. Quintessence International 1978;9:63-6.
Lieser 1978 {published data only}
  • Lieser O, Schmidt HF. Caries preventive effect of fluoride lacquer after several year's use in children [Kariesprophylaktische Wirkung von Fluorlack nach mehrjahriger Anwendung in der Jugendzahnpflege]. Deutsche Zahnarztliche Zeitschrift 1978;33:176-8.
Lindquist 1989 {published data only}
  • Lindquist B, Edward S, Torell P, Krasse B. Effect of different carriers preventive measures in children highly infected with mutans streptococci. Scandinavian Journal of Dental Research 1989;97:330-7.
Maiwald 1974 {published data only (unpublished sought but not used)}
  • Maiwald HJ. Topical application of fluoride varnish for dental caries prevention in collectives following a 3-year testing period [Lokalapplikation von Fluorschulzlack zur Kariespravention in Kollektiven nach dreij''ahriger Kontrollzeit]. Stomatologie der DDR 1974;24:123-5.
  • Maiwald HJ, Geiger L. Local application of fluorine protective varnish for caries prevention in collectivities [Lokalapplikation von Fluorschutzlack zur Kariesprophylaxe in Kollektiven]. Deutsche Stomatologie 1973;23:56-63.
Maiwald 1978 {published data only}
  • Maiwald HJ, Kunzel W, Weatherell J. The use of a fluoride varnish in caries prevention. Journal of the International Association of Dentistry for Children 1978;9:31-5.
Mari 1988 {published data only}
  • Mari A, Toth K, Kiss Z, Szita V. The effect of Fluor Protector lacquer on the primary and permanent teeth in children consuming fluoridated table salt [A Fluor Protector lakk hatasa fluorozott sot fogyaszto gyermekek tej- es maradofogazatanak allapotara]. Fogorvosi Szemle 1988;81:225-30.
Mari 1988a {published data only}
  • Mari A, Toth K, Kiss Z, Savay G. The effect of Duraphat lacquer on the condition of the permanent teeth in children consuming fluoridated table salt [A Duraphat lakk hatasa fluorozott sot fogyaszto gyermek maradofogazatanak allapotara]. Fogorvosi Szemle 1988;81:169-74.
Murray 1977 {published data only}
Pashaev 1977 {published data only}
  • Pashaev KP. Comparative assessment of the caries prevention effectiveness of different fluorine preparations [Sravnitel'naia otsenka kariesprofilakticheskoi effektivnosti razlichnykh preparatov ftora]. Stomatologiia Mosk 1977;56:82-4.
Petersson 1998 {published data only}
Ramos 1995 {published data only}
  • Ramos SB. Effect of Fortnightly Rinsing with a 0.2 per cent NaF Solution and a Fluoride Varnish with 5 per cent NaF in Dental Caries Prevention: Comparative Study in Students of the Northern Region of Sao Paulo city, Brazil, 1992-1993 [Thesis]. Sao Paulo, Brazil: Universidade de Sao Paulo, 1995.
Ramos-Gomez 2012 {published data only}
  • Ramos-Gomez FJ, Gansky SA, Featherstone JD, Jue B, Gonzalez-Beristain R, Santo W, et al. Mother and youth access (MAYA) maternal chlorhexidine, counselling and paediatric fluoride varnish randomized clinical trial to prevent early childhood caries. International Journal of Paediatric Dentistry 2012;22(3):169-79.
Riethe 1977 {published data only}
  • Riethe P, Streib W, Schubring G. Clinical trials of Nuva Seal, Epoxylite 9070 and Fluor-Protector [Klinische Untersuchungen mit Nuva Seal, Epoxylite 9070 und Fluor-Protector]. Deutsche Zahnarztliche Zeitschrift 1977;32:853-5.
Rodríguez Miró 1988 {published data only}
  • Rodríguez Miró MJ, Vega Valdés D. Evaluation of semiannual combined-treatment with fluoride-chlorhexidine varnish and toothbrushing with chlorhexidine toothpaste for 15 days every 3 months in hypercariogenic children [Valoración del tratamiento combinado de aplicaciones semestrales de barniz-flúor-clorhexidine y del cepillado dental por 15 días cada tres meses con la crema dental con clorhexidine en niños hipercariogénicos]. Revista Cubana de Estomatología 1988;25(3):28-35.
Ruszynska 1978 {published data only}
  • Ruszynska H, George B, Anholcer H, Haber Milewska T. Clinical evaluation of fluor-protector varnish in dental caries prevention [Badania kliniczne nad skutecznoscia stosowania lakieru fluor-protektor w zapobieganiu prochnicy]. Czasopismo Stomatologiczne 1978;31:1021-5.
Salem 1979 {published data only}
  • Salem LV, Raschio AJ, Montoya VC. [Klinische untersuchung über die karieshemmende langzeitwirkung des Fluor-Protector-Lackes]. Kariesprophylaxe 1979;1:145-8.
Schioth 1981 {published data only}
  • Schioth JT. Effect of fluoride lacquering on the need of dental care in a group of adolescent school pupils [Effekten av fluorlakkering pa tannbehandlings-behovet hos en gruppe ungdomsskoleelever]. Norske Tannlaegeforenings Tidende 1981;91:123-6.
Schmidt 1970 {published data only}
  • Schmidt HF. Caries prophylaxis by means of local application of sodium fluoride with special reference to long term fluoridation [Untersuchungen zur Prophylaxe der Zahnkaries durch ortliche Applikation von Natriumfluorid unter besonderer Berucksichtigung der Langzeitfluoridierung]. Stoma Heidelb 1970;23:5-40.
Seppä 1982 {published data only}
  • Birkeland JM. Trials - results - conclusions. Duraphat - Fluor Protector [Forsok - funn - konklusjon. Duraphat - Fluor Protector]. Den Norske Tannlaegeforenings Tidende 1981;91(10):368-9.
  • Seppä L, Hausen H, Luoma H. Relationship between caries and fluoride uptake by enamel from two fluoride varnishes in a community with fluoridated water. Caries Research 1982;16:404-12.
  • Seppä L, Hausen H, Tuutti H, Luoma H. Effect of a sodium fluoride varnish on the progress of initial caries lesions. Scandinavian Journal of Dental Research 1983;91:96-8.
  • Seppä L, Tuutti H, Luoma H. A 2-year report on caries prevention by fluoride varnishes in a community with fluoridated water. Scandinavian Journal of Dental Research 1981;89:143-8.
  • Seppä L, Tuutti H, Luoma H. Post-treatment effect of fluoride varnishes in children with a high prevalence of dental caries in a community with fluoridated water. Journal of Dental Research 1984;63:1221-2.
  • Seppä L, Tuutti H, Luoma H. Three-year report on caries prevention of using fluoride varnishes for caries risk children in a community with fluoridated water. Scandinavian Journal of Dental Research 1982;90:89-94.
Shobha 1987 {published data only (unpublished sought but not used)}
  • Shobha T, Nandlal B, Prabhakar AR, Sudha P. Fluoride varnish versus acidulated phosphate fluoride for schoolchildren in Manipal. Journal of the Indian Dental Association 1987;59:157-60.
Slade 2011 {published data only}
  • Roberts-Thomson KF, Slade GD, Bailie RS, Endean C, Simmons B, Leach AJ, et al. A comprehensive approach to health promotion for the reduction of dental caries in remote Indigenous Australian children: a clustered randomised controlled trial. International Dental Journal 2010;60(3 Suppl 2):245-9.
  • Slade GD, Bailie RS, Roberts-Thomson K, Leach AJ, Raye I, Endean C, et al. Effect of health promotion and fluoride varnish on dental caries among Australian Aboriginal children: results from a community-randomized controlled trial. Community Dentistry and Oral Epidemiology 2011;39(1):29-43.
Splieth 2000 {published data only}
  • Splieth CH, Baekken S, Rosin M. Effectiveness of different topical fluoride applications in schoolchildren. European Journal of Paediatric Dentistry 2000;1:107-42.
Suntsov 1991 {published data only}
  • Suntsov VG, Distel' VA, Zhorova TN, Buiankina RG, Toropov VN, Bulanova EL, et al. The trace efficacy of dental caries prevention in children [Sledovaia effektivnost' profilaktiki kariesa zubov u detei]. Stomatologiia Mosk 1991;(2):69-71.
Suwansingha 2011 {published data only}
  • Suwansingha O, Rirattanapong P. Effect of fluoride varnish on caries prevention of partially erupted of permanent molar in high caries risk. The Southeast Asian Journal of Tropical Medicine and Public Health 2012;43(3):808-13.
Todorashko 1983 {published data only}
  • Todorashko OV. Results of the combined use of remodent and fluorine lacquer for dental caries prevention in preschoolers [Rezul'taty sochetannogo primeneniia remodenta i ftorlaka dlia profilaktiki kariesa zubov u doshkol'nikov]. Stomatologiia Mosk 1983;62:12-3.
Tranaeus 2001 {published data only}
  • Tranaeus S, Al-Khateeb S, Björkman S, Twetman S, Angmar-Månsson B. Application of quantitative light-induced fluorescence to monitor incipient lesions in caries-active children. A comparative study of remineralisation by fluoride varnish and professional cleaning. European Journal of Oral Sciences 2001;109:71-5.
Treide 1980 {published and unpublished data}
  • Treide A, Hebenstreit W, Gunther A. Collective preschool caries prevention using a fluoride-containing varnish [Kollektive Kariespravention im Vorschulalter unter Verwendung eines fluoridhaltigen Lackes]. Stomatologie der DDR 1980;30:734-9.
van Eck 1984 {published data only (unpublished sought but not used)}
  • Groeneveld A, Theuns HM, Kwant GW. Effect of a fluoride-containing lacquer on dental caries. Journal of Dental Research 1982;61:569.
  • Theuns HM, Groeneveld A, van Eck AA. Clinical experimental field trials of the caries-preventive effect of a fluoride lacquer [Een klinisch experimenteel veldonderzoek naar het caries- preventieve effect van een fluoridelak]. Netherlands Tijdschrift voor Tandheelkunde 1985;92:66-9.
  • van Eck AA, Theuns HM, Groeneveld A. Effect of annual application of polyurethane lacquer containing silane-fluoride. Community Dentistry and Oral Epidemiology 1984;12:230-2.
Wacińska-Drabińska 1987 {published data only}
  • Wacińska-Drabińska M. Effect of Fluor-Protector varnish on the inhibition of the carious process in milk teeth [Wplyw lakieru Fluor-Protector na zahamowanie procesu prochnicowego w zebach mlecznych]. Czasopismo Stomatologiczne 1987;40(8):528-32.
Wegner 1976 {published data only}
  • Wegner H. The clinical effect of application of fluoride varnish. Caries Research 1976;10:318-20.
Winter 1975 {published data only}
  • Winter K. Caries prophylaxis by local application of sodium fluoride lacquer [Kariesprophylaxe durch Lokalapplikation von Natriumfluorid-Lack]. Zahnarztlicher Gesundheitsdienst 1975;(3):1-2.
  • Winter K. Caries prophylaxis by means of local application of sodium fluoride lacquer [Kariesprophylaxe durch Lokalapplikation von Natriumfluorid-Lack]. Zahnarztliche Mitteilungren 1975;65:215-21.
Wojtowicz 1986 {published data only}
  • Wojtowicz D, Banach J. Clinical evaluation of Duraphat varnish in the prevention of dental caries in children and in the control of cervical hypersensitivity in adults [Ocena kliniczna laku Duraphat w profilaktyce prochnicy zebow u dzieci oraz w zwalczaniu wrazliwosci szyjek zebow u doroslych]. Czasopismo Stomatologiczne 1986;39:213-8.
Xhemnica 2008 {published data only}
  • Xhemnica L, Sulo D, Rroço R, Hysi D. Fluoride varnish application: a new prophylactic method in Albania. Effect on enamel carious lesions in permanent dentition. European Journal of Paediatric Dentistry 2008;9:93-6.
Zimmer 1999 {published data only}

References to ongoing studies

  1. Top of page
  2. Abstract
  3. Summary of findings
  4. Background
  5. Objectives
  6. Methods
  7. Results
  8. Discussion
  9. Authors' conclusions
  10. Acknowledgements
  11. Data and analyses
  12. Appendices
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Sources of support
  18. Differences between protocol and review
  19. Characteristics of studies
  20. References to studies included in this review
  21. References to studies excluded from this review
  22. References to ongoing studies
  23. Additional references
  24. References to other published versions of this review
Macpherson 2012 {unpublished data only}
  • Macpherson L. Comparison of the caries-protective effect of fluoride varnish (Duraphat®) with treatment as usual in nursery school attendees receiving preventive oral health support through the Childsmile Oral Health Improvement Programme: an RCT. http://clinicaltrials.gov/show/NCT01674933.

Additional references

  1. Top of page
  2. Abstract
  3. Summary of findings
  4. Background
  5. Objectives
  6. Methods
  7. Results
  8. Discussion
  9. Authors' conclusions
  10. Acknowledgements
  11. Data and analyses
  12. Appendices
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Sources of support
  18. Differences between protocol and review
  19. Characteristics of studies
  20. References to studies included in this review
  21. References to studies excluded from this review
  22. References to ongoing studies
  23. Additional references
  24. References to other published versions of this review
Ammari 2003
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