Pit and fissure sealants versus fluoride varnishes for preventing dental decay in the permanent teeth of children and adolescents

Summary of findings 1. Resin‐based fissure sealant compared with fluoride varnish for preventing dental caries

Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	Number of participants (studies)	Certainty of the evidence (GRADE)	Comments
Resin‐based fissure sealant compared with fluoride varnish for preventing dental caries
Population: children and adolescents Setting: preventive dentistry Intervention: resin‐based fissure sealant applications on occlusal tooth surfaces of permanent first molars Comparison: fluoride varnish applications on occlusal tooth surfaces of permanent first molars
	Assumed risk	Corresponding risk
	Fluoride varnish	Resin‐based fissure sealant
Dentine caries in permanent molars (yes/no) Follow‐up: 2–3 years	228 per 1000	63 fewer per 1000 (from 32 more to 129 fewer)	OR 0.67 (95% CI 0.37 to 1.19)	1683 (4 studies)	⊕⊝⊝⊝ Very low^a,b,c	Data from 1 other study measuring DMFS and DMFT suggested a very small benefit for fissure sealants at 2‐year follow‐up. 4‐ and 9‐year data came from 1 study at high risk of bias and suggested a benefit for fissure sealants.
Adverse effects	None reported
The basis for the assumed risk* was the median risk in the fluoride varnish group. 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; DMFS: decayed, missing and filled permanent surfaces; DMFT: decayed, missing and filled permanent teeth; OR: odds ratio.
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.
^aDowngraded one level as studies at high risk of detection bias. ^bDowngraded one level due to severe heterogeneity (I² = 84%). ^cDowngraded one level for imprecision.

Summary of findings 2. Glass ionomer fissure sealant or resin‐modified glass ionomer fissure sealant compared with fluoride varnish for preventing dental caries

Outcomes	Results	Number of participants (studies)	Certainty of the evidence (GRADE)	Comments
Glass ionomer fissure sealant or resin‐modified glass ionomer fissure sealant compared with fluoride varnish for preventing dental caries
Population: children and adolescents Setting: preventive dentistry Intervention: glass ionomer or resin‐modified glass ionomer sealant applications on occlusal tooth surfaces of permanent first molars Comparison: fluoride varnish applications on occlusal tooth surfaces of permanent first molars
Dentine caries in permanent molars Follow‐up: 1, 2 and 3 years	No evidence of a difference between interventions in caries after 1, 2 and 3 years	995 (3 studies)	⊕⊝⊝⊝ Very low^a,b,c,d	Studies were clinically different so we did not combine them in meta‐analyses. 1 study included oral health education in both arms and found a benefit for sealant among children at high risk of caries.
Adverse effects	None reported
The basis for the assumed risk* (e.g. 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).
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.
^aOne study with high risk of bias comparing resin‐modified glass ionomer versus fluoride varnish after 1 year (Florio 2001). ^bThe other two studies at two years, with incomplete information and analyses, compared chemically cured glass ionomer versus fluoride varnish (Ji 2007). The third study actually evaluated whether additional benefit was derived by using resin‐modified glass ionomer sealants and fluoride varnishes among children receiving regular oral health education (Tagliaferro 2011). ^cOne study at three years comparing chemically cured glass ionomer versus fluoride varnish, assessed as having high risk of bias (extensive incomplete information and analyses) (Ji 2007). ^dDowngraded because a small number of trials had high risk of bias and used different designs and follow‐up times.

Summary of findings 3. Resin‐based fissure sealant plus fluoride varnish versus fluoride varnish alone for preventing dental caries

Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	Number of participants (studies)	Certainty of the evidence (GRADE)	Comments
Resin‐based fissure sealant plus fluoride varnish compared with fluoride varnish alone for preventing dental caries
Population: children and adolescents at school in Germany Setting: preventive dentistry Intervention: resin‐based fissure sealant + fluoride varnish applications on occlusal tooth surfaces of permanent first molars Comparison: fluoride varnish applications to occlusal tooth surfaces of permanent first molars
	Assumed risk	Corresponding risk
	Fluoride‐varnished teeth	Sealed + fluoride‐varnished teeth
Dentine caries in permanent molars Follow‐up: 2 years	223 per 1000	144 fewer per 1000 (from 87 fewer to 176 fewer)	OR 0.30 (95% CI 0.17 to 0.55)	92 (1 study)	⊕⊝⊝⊝ Very low^a,b,c	—
Adverse effects	Not measured
The basis for the assumed risk* (e.g. 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; OR: odds ratio.
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.
^aStudy conducted in the 1990s (Splieth 2001). ^bNo information on caries incidence among control teeth without treatment. Baseline caries of the study population (children five to eight years of age): mean decayed, missing and filled permanent surfaces 0.2. ^cDowngraded three levels because a single study (92 analysed participants) was conducted as early as the 1990s without information on caries incidence among control teeth without treatment, and although the study was otherwise well conducted, lack of blinding to outcome measurement caused further uncertainty about results.

Background

Description of the condition

Dental caries is a multi‐factorial chronic oral disease that affects most populations throughout the world and has been considered the most important global oral health burden (Petersen 2005). Since the 1970s, a reduction in caries prevalence has occurred in most industrialised countries; and has been attributed to improvements in living conditions and oral hygiene, and public health measures such as widespread use of fluoride tooth paste, fluoride products and better disease management (Splieth 2016). However, dental caries is still a problem for some individuals and populations, for example, in many Eastern European and South American countries, the prevalence of caries among 12‐year‐olds has been reported to be moderate or high (WHO 2014). Dental caries incidence is still considered very high despite the decline in the severity of dentine caries and the slower rate of caries progression into dentine amongst children below the age of 12 years (Frencken 2017).

Dental caries can be explained as an interplay between specific acidogenic bacteria in the plaque biofilm, fermentable carbohydrates and tooth structure. The biofilm bacteria produce organic acids that can cause loss of minerals from the tooth surface (demineralisation). In favourable conditions, a reversal, that is, a mineral gain, is possible (remineralisation). If the demineralisation process prevails, visually detectable caries lesions occur. Development of a caries lesion is a dynamic process that may progress, stop or reverse, and assessment of the grade and activity of the lesion is challenging. The International Caries Detection and Assessment System (ICDAS) integrates a definition of dental caries and a system to measure the caries process (ICDAS 2008). In ICDAS, the codes for coronal caries range from 0 to 6, depending on the severity of the lesion: codes from 0 to 3 involve a sound tooth surface to caries in enamel (with or without micro‐cavitation); codes 4 to 6 involve caries in dentine.

For permanent teeth, caries lesion development is most likely in the first few years after the tooth erupts (Carvalho 2014; Mejàre 2014). Most of the detected increment in dental caries among children above six years of age and adolescents is confined to the pit and fissure surfaces of first molars (Batchelor 2004; Brown 1995; McDonald 1992); their anatomy favours biofilm formation and retention and carious lesions often start before teeth fully erupt (Alves 2014; Zenkner 2013). However, the occlusal surfaces of second permanent molars are also vulnerable. The rate of occlusal caries among young people has not fallen as much as the rate of caries on smooth surfaces (Brown 1995).

The efficacy of any caries‐preventive intervention depends on the actual caries risk of an individual (and population), that is, if the risk of developing new lesions within a certain follow‐up period is small even without intervention, then any efficacy estimate of the additional preventive method will be small. Current methods for caries risk assessment comprise a range of strategies such as past caries experience, information about sociodemography, oral hygiene and dietary habits, oral bacteria and saliva characteristics (Mejàre 2014). However, the factors are not stable, for example, oral hygiene and dietary habits can change during follow‐up, decreasing or increasing caries risk.

The evidence on the validity of existing systems to predict future caries risk is limited (Tellez 2013). A review by Twetman 2016, summarising the findings of systematic reviews, concluded that there is no clearly superior method to predict future caries, whereas a systematic review by Mejàre 2014 found that baseline caries experience of the child was the most accurate single predictor for future caries development (moderate/good accuracy in preschool children and limited accuracy in school children/adolescents).

Oral disorders affect 3.5 billion people worldwide, with substantial burden on quality of life, as well as costs to the healthcare system, patients and society. In 2015 alone, the estimated direct costs of providing dental health care were USD 356.8 billion, corresponding to 4.6% of global health expenditure, with a further estimated USD 187.6 billion in indirect costs (Righolt 2018). Much of that expenditure is used to treat largely preventable disease among children and adolescents, with significant cost burden to healthcare payers (patients, governments, insurance). In 2015/2016 alone, tooth decay was the most common reason for hospitalisation among children aged five to nine years in England (Public Health England 2019). In 2018/2019 the national schedule of reference costs data for England, covering secondary care costs, indicated that over 70,000 episodes of care took place to deal with surgical extraction of teeth in people aged 18 years and under, at a total cost of GBP 65.7 million, at a mean cost per procedure of GBP 932, weighted for procedure complexity. A further GBP 4.3 million was spent on hospital‐provided restorations for children (NHS England). There are also substantial costs to primary dental care services. In Scotland, 2018/2019 data showed that there were 186,179 permanent fillings, 4002 endodontics treatments and 136,459 extractions (treatment codes 14, 15, 21) provided for children in primary dental care alone at a total cost of almost GBP 4 million (Public Health Scotland 2019). The cost burden further extends to families with respect to time off work, childcare, lost school days and to society in terms of lost productivity for time spent taking children to receive avoidable complex dental care.

Description of the intervention

Dental sealants

Dental sealants were introduced for preventing caries on occlusal surfaces, but are now considered active agents for controlling and managing initial caries lesions on occlusal surfaces (Splieth 2010), and on approximal surfaces (Dorri 2015; Ekstrand 2012; Splieth 2010). There are numerous occlusal sealant materials, but resins/composites and glass ionomers comprise the main material types.

Options of occlusal sealant materials are numerous but resins/composites and glass ionomers comprise the main material types. A resin material, bisphenol A glycidyl methacrylate (BIS‐GMA), forms the basis for numerous resin‐based dental sealants and composites that are now available. The effectiveness of resin‐based sealants is closely related to the longevity of sealant coverage (i.e. clinical retention) (Ripa 1993). The development of sealants has progressed from first‐generation sealants, which were activated with ultraviolet light, through to second‐ and third‐generation sealants, which are autopolymerised and visible‐light activated, and fourth‐generation sealants, which contain fluoride. First‐generation sealants are no longer marketed. Reports have considered possible adverse oestrogen‐like effects of resin‐based materials including bisphenol A (BPA) (e.g. Azarpazhooh 2008a; Fleisch 2010; Joskow 2006). This synthetic chemical resin is widely used in the production of plastic products intended for everyday use, but its use in dental materials is quite rare (ADA 2003). Although some dental resins can include low‐levels of BPA (e.g. trace material from resin production) (ADA 2016), evidence suggests that use of these resin‐based sealants does not place people at risk of harmful effects (ADA 2016; Azarpazhooh 2008a; Fleisch 2010).

The other main type of sealant is made from glass ionomer cements (combination of silicate and polyacrylate cement system). There is a wide range of glass ionomer materials available. Glass ionomer cements may be used as the original chemically cured type or as the light‐cured type, which is modified with resin, for example, for rapid initiation of the curing process (resin‐modified glass ionomers).

Novel materials called compomers, which were introduced in the 1990s to combine benefits of resins and those of glass ionomer cements, have also been applied as sealants (Nicholson 2007; Ruse 1999).

Allergic reactions to sealant materials are possible but rare (Hallstrom 1993).

Fluoride varnishes

The aim of topical fluoride varnish application is to treat hard tooth surfaces in such a way that caries is arrested or reversed. Although fluoride varnishes have a very high fluoride concentration (e.g. 22,660 ppm in Duraphat fluoride varnish), their use is considered safe because they have a quick‐setting base, release fluoride slowly over time and require comparatively small amounts of varnish for the whole dentition (Petersson 1993). Only a small dose of fluoride is swallowed over several hours, and risk of acute toxic reactions (e.g. nausea, vomiting) is minimal (Bawden 1998; Seppä 1999). Contact allergies to fluoride varnish due to colophony are possible but have been reported in only two cases (Chu 2006; Isaksson 1993).

Sometimes topical fluoride has been combined with sealant application to strengthen overall effectiveness in the prevention of dental caries.

How the intervention might work

Fluoride acts to prevent caries in three ways: 1. by inhibiting the demineralisation, 2. promoting the remineralisation of dental enamel and 3. by inhibiting acid formation by plaque bacteria (Shellis 1994; Ten Cate 1997). It can be applied in various ways; a varnish has the advantage of relative longevity. Dental sealant is applied to a tooth surface to provide a physical barrier that prevents growth of biofilm by blocking nutrition. Resin‐based and composite materials are used most commonly, with glass ionomer cements having the added element of containing fluoride that is released over a prolonged period.

The cost of preventive care is small in comparison to the extensive cost to primary, but especially secondary, care services of complex restorative and surgical dental treatment. Therefore, if preventive measures, such as fissure sealants or fluoride varnish, can demonstrate effectiveness in terms of reduced tooth decay, and can avert long‐term need for restorations and extractions, there is great potential for cost savings to payers (insurance, patients and the health system) and cost‐effectiveness.

Why it is important to do this review

Cochrane Oral Health undertook an extensive prioritisation exercise in 2014 and this review was identified as a priority title by the paediatric dentistry expert panel (see oralhealth.cochrane.org/priority-reviews) (Worthington 2015). Several systematic reviews have shown the substantial effectiveness of resin‐based sealants and fluoride varnishes in preventing or controlling occlusal decay as compared with no intervention (sealants: Ahovuo‐Saloranta 2017; Griffin 2008; Llodra 1993; Mejàre 2003; varnish: Azarpazhooh 2008b; Helfenstein 1994; Marinho 2013; Petersson 2004), but the relative effectiveness remains unclear. Application of sealants is more technique sensitive than application of fluoride varnish; however, sealants usually are applied only once and should be reapplied if failed and maintained based on caries risk, whereas fluoride varnish is applied several times, depending on the caries activity of an individual.

Statement on cost‐effectiveness of these preventive measures

To make evidence‐based decisions about the effective and efficient allocation of scarce funding resources, policy makers require information about the potential cost‐effectiveness of different preventive interventions to determine if the additional money spent on prevention is an effective and efficient use of scarce funding resources in the longer term. It is also necessary to determine which preventive measures are the most cost‐effective (can achieve greatest benefit for least cost) to ensure dental funding is allocated in the most efficient way possible. This review includes a brief economic commentary (BEC) to add an economic lens to the interpretation of the results.

The aim of this systematic review is to compare the relative effectiveness of fissure sealants and fluoride varnishes alone, or fissure sealants combined with fluoride varnishes and fluoride varnishes alone, for preventing dental caries in children and adolescents.

Objectives

Primary objective

To evaluate the relative effectiveness of dental sealants (i.e. fissure sealant) compared with fluoride varnishes, or fissure sealants plus fluoride varnishes compared with fluoride varnishes alone, for preventing dental caries in the occlusal surfaces of permanent teeth of children and adolescents.

Secondary objectives

To evaluate whether effectiveness is influenced by sealant material type and length of follow‐up.
To document and report on data concerning adverse events associated with sealants and fluoride varnishes.
To report the cost effectiveness of dental sealants versus fluoride varnish in caries prevention.

Methods

Criteria for considering studies for this review

Types of studies

We included randomised controlled trials (RCTs) with at least of 12 months' follow‐up, in which fissure sealants, or fissure sealants plus fluoride varnishes, were compared with fluoride varnishes alone for preventing caries in occlusal surfaces of permanent teeth of children and adolescents. We included both parallel‐group and split‐mouth study designs. The unit of randomisation could be the individual, the group (e.g. school, school class), or the tooth or tooth pair.

Types of participants

Children and adolescents from the general population, younger than 20 years of age at the start of the study.

Types of interventions

Pit and fissure sealants of all materials (except first‐generation resin‐based sealants) versus fluoride varnish.
Pit and fissure sealants plus fluoride varnish versus fluoride varnish.

Intervention group was either the sealant group or the sealant plus fluoride varnish group. The control group was the fluoride varnish group.

We included studies in which applications were placed on occlusal surfaces of permanent posterior teeth for the purpose of preventing caries, regardless of who did the application. Materials could be applied on sound surfaces or on enamel lesions (if scored using the ICDAS II scale, codes 0, 1, 2 and 3 were accepted). The sealant application method used in the study could consist of direct application to the tooth surface or application after mechanical preparation of the enamel surface.

Types of outcome measures

Primary outcomes

Occurrence of new dentinal carious lesions on treated occlusal surfaces of molars or premolars observed within 12 months from the initial treatment: assessed by visual‐tactile clinical assessment as a dichotomous measure using the participant as the unit of analysis in parallel studies and the tooth pair within an individual to be the unit of measurement (yes or no) in split‐mouth studies.
Changes from baseline in decayed, missing and filled (DMF) figures at surface, tooth and whole‐mouth levels.
Progression of dentinal carious lesions into dentine on treated occlusal surfaces of molars or premolars, observed within 12 months from the initial treatment: assessed by visual‐tactile clinical assessment as a dichotomous measure using a tooth/individual/pair of teeth as the unit of measurement.

Secondary outcomes

Time taken to apply pit and fissure sealant or fluoride varnish (minutes).
Number of visits to the dentist for repair of sealant or fluoride varnish application.
Safety of using sealants and fluoride varnishes assessed by presence or absence of adverse events.

Search methods for identification of studies

Electronic searches

Cochrane Oral Health's Information Specialist conducted systematic searches in the following databases for RCTs and controlled clinical trials (CCTs). There were no language, publication year or publication status restrictions:

Cochrane Oral Health's Trials Register (searched 19 March 2020) (Appendix 1);
Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 2) in the Cochrane Library (searched 19 March 2020) (Appendix 2);
MEDLINE Ovid (1946 to 19 March 2020) (Appendix 3);
Embase Ovid (1980 to 19 March 2020) (Appendix 4).

Subject strategies were modelled on the search strategy designed for MEDLINE Ovid. Where appropriate, they were combined with subject strategy adaptations of the highly sensitive search strategy designed by Cochrane for identifying RCTs and CCTs as described in the Cochrane Handbook for Systematic Reviews of Interventions Chapter 6 (Lefebvre 2011).

Searching other resources

We searched the following trial registries for ongoing studies (see Appendix 5):

US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov (clinicaltrials.gov; searched 19 March 2020);
World Health Organization (WHO) International Clinical Trials Registry Platform (apps.who.int/trialsearch; searched 19 March 2020).

We searched the reference lists of included studies and relevant systematic reviews for further studies.

We checked that none of the included studies in this review were retracted due to error or fraud.

We did not perform a separate search for adverse effects of interventions used; we considered adverse effects described in included studies only.

On 19 March 2020, Cochrane Oral Health's information specialist undertook an additional search for cost‐effectiveness studies. MEDLINE Ovid and Embase Ovid were searched using the search strategies presented in Appendix 6.

For previous versions of this review, we also searched SCISEARCH, CAplus, INSPEC, JICST‐EPLUS, NTIS, PASCAL, DARE, HTA and OpenSIGLE (see Appendix 7). However, we decided not to update these searches at this time because in previous versions of the review, these searches yielded no additional information.

Data collection and analysis

Selection of studies

The 2020 update search results were imported into Covidence. Two review authors (WK, PG) independently selected papers on the basis of title, keywords and abstract, and decided on eligibility. The search was designed to be sensitive and include controlled clinical trials; these were filtered out early in the selection process if they were not randomised. We obtained the full text of every study considered for inclusion. If information relevant to the inclusion criteria was not available in the abstract, or if the title was relevant but the abstract was not available, we obtained the full text of the report. Two review authors (WK, PG) independently gathered information and recorded data, and resolved disagreements by discussion with a third review author (HW).

We contacted trial authors to request additional information if the study seemed to fulfil the inclusion criteria for this review but information in the report was insufficient to allow final assessment of inclusion or exclusion. We sought translation for one Dutch trial (Vermaire 2015)), which we later excluded, and one Chinese study (Tang 2014), which is included in this review.

We decided to consider only studies with a full‐text report. We excluded studies reported only as abstracts because methodological research has suggested discrepancies between data reported in an abstract and those provided in the final published full report, and because information on trial quality indicators is often lacking (Chokkalingam 1998; Hopewell 2006). Thus, we decided that the full‐text report was required to ensure reliable data extraction and assessment of risk of bias. To diminish the risk of publication bias, we contacted authors of relevant abstracts to ask whether a full‐text report of the study (unpublished or published) was available.

Data extraction and management

Two review authors (WK, PG) independently extracted relevant data from included studies. The two review authors were in full agreement about data, and discussion with a third review author was not needed. We attempted to contact study authors to request missing information or clarification when necessary.

We extracted the following information on study methods.

Trial design.
Study duration (years of follow‐up).
Year the study began.

We extracted the following characteristics of participants.

Location where study was conducted (country and setting where participants were recruited).
Criteria for accepting participants into the study (intact surfaces and surfaces with enamel lesion allowed).
Age (range and mean age at start) and sex.
Baseline caries prevalence of participants (caries severity at start (mean number of decayed, missing and filled deciduous teeth (dmft); decayed, missing and filled deciduous surfaces (dmfs); decayed, missing and filled permanent surfaces (DMFS); decayed, filled permanent surfaces (DFS); or other measure)).
Number of randomly assigned participants and number of teeth in treatment at study start and follow‐up.
Number of evaluated participants.

We extracted the following characteristics of interventions.

Intervention comparisons (sealant versus fluoride varnish, or sealant plus fluoride varnish versus fluoride varnish).
Sealant and fluoride varnish products used in the study.
Reapplication of sealants and frequency of fluoride varnish application.
Information on who applied sealants and fluoride varnishes (dentist with or without assistant or dental hygienist).
Co‐interventions (e.g. background exposure to other fluoride sources (toothpaste, water, etc.)).

We extracted the following characteristics of outcomes.

Description of outcomes.
Description of outcome measurements.

We extracted the following additional information.

Information related to calibration of examiners and kappa statistics.
Sealant retention figures at follow‐up.
Funding source.
Caries prevalence of population in study area.

Outcome information was extracted for the number of dentinal carious lesions or non‐carious lesions on occlusal surfaces of treatment and control teeth at different follow‐up times. If a filling had been put on the occlusal surface or the tooth had been extracted as the result of caries during the study, we coded it as caries. If the data were not presented in tables, we extracted data presented in graphs and figures when needed.

We presented data from the included studies in Table 1. For the split‐mouth studies, we extracted the 2×2 cross tabulation for the paired data, or the incorrectly reported simple prevalence by independent group, prior to calculation of the treatment effects. For the cluster trial, we obtained the cluster corrected effect estimates and standard errors from the authors.

Table 1. Caries data from studies with binary outcome

Resin FS vs FV: at 2–3 years
Split‐mouth studies	Both sound	FS sound FV carious	FS carious FV sound	Both carious	Proportion of decayed FV tooth surfaces to total FV surfaces	Becker‐Balagtas marginal OR (95% CI)
Raadal 1984 (sealant better)	131	31	15	31	0.30	0.67 (0.48 to 0.93) P = 0.02 ICC 0.44
Parallel‐group studies	Description of data					OR (95% CI)
Bravo 2005 (sealant better)	Calculated OR from data presented in Bravo 1996 (25/238 occlusal surfaces carious in sealant group; 71/252 surfaces carious in fluoride varnish group)					0.30 (0.18 to 0.49)
Liu 2012 (no difference)	OR based on model of multi‐level GEE logistic regression Additional information obtained from study author 124 children in sealant group, 116 in varnish group					0.87 (0.34 to 2.20)
Chestnutt 2017 (no difference)	The results presented as the proportion of children who developed dentine caries (D_4-6MFT) on ≥ 1 FPM at 36 months (19.6% in FS arm and 17.5% in FV arm). Sex and baseline caries prevalence were used to balance the randomisation. An adjusted model was also performed and taken as the primary analysis. 418 children in sealant group, 417 in varnish group					1.15 (0.81 to 1.63)
Pooled						OR 0.67 (0.37 to 1.19)
Resin FS vs FV: 4 years
Parallel‐group studies	Description of data					RR (95% CI)
Bravo 2005 (sealant better)	Results presented as RRs with cluster‐corrected standard error. A school class is a cluster, but several sealed and fluoride‐varnished teeth were present per child. Study authors calculated cluster‐corrected effect estimates when requested.					0.42 (0.21 to 0.84) P = 0.01
Resin FS vs FV: 9 years
Parallel‐group studies	Description of data
Bravo 2005 (sealant better)	Results presented as RRs with cluster‐corrected standard error. A school class is a cluster, but several sealed and fluoride‐varnished teeth were present per child. Study authors calculated cluster‐corrected effect estimates when requested. 26.6% of FS teeth and 55.8% of FV teeth had developed caries after 9 years (76.7% of control teeth without treatments)					0.48 (0.29 to 0.79) P = 0.004
Resin‐modified glass ionomer FS vs FV: 1 year
Parallel‐group studies	Description of data					OR (95% CI)
Florio 2001 (no difference)	Clustered data (several teeth per child). Data decided to analyse at a child level (i.e. data were dichotomised – did a child have caries or not) because decayed teeth were very few. Additional information obtained from study author indicated that the 2 decayed surfaces in the FV group were present in different children. 31 children in sealant group, 11 in varnish group Detailed data (Analysis 2.1)					0.18 (0.01 to 4.27) P = 0.29
Resin FS + FV vs FV: 2 years
Split‐mouth studies	Both sound	FS + FV sound FV carious	FS + FV carious FV sound	Both carious	Proportion of decayed control tooth surfaces to total control surfaces	Becker‐Balagtas marginal OR (95% CI)
Splieth 2001 (FS + FV better than FV alone)	129	32	7	7	0.22	0.30 (0.17 to 0.55) P < 0.0001

CI: confidence interval; FPM: first permanent molar; FS: fissure sealant; FV: fluoride varnish; GEE: generalised estimating equation; ICC: intracluster correlation coefficient; OR: odds ratio.

In addition, we recorded caries increments as changes in decayed, missing and filled permanent surfaces (DMFS)/decayed, missing and filled permanent teeth (DMFT) scores and as progression of caries lesions in enamel or dentine when study authors reported them. We recorded the following secondary outcomes when reported: time taken to apply pit and fissure sealant or fluoride varnish and number of visits to the dentist for repair or reapplication of sealant or fluoride varnish application. We recorded any adverse events reported, such as signs of allergic reaction (tingling, swelling, skin rash) or any other symptoms if it occurred within the first 24 hours of application of the intervention, or any longer‐term adverse events.

In some studies, results were provided at more than one period of follow‐up. We extracted data at one, two, three, four, five years, etc. (annually), and based our analyses on available data at these preselected times.

Assessment of risk of bias in included studies

Two review authors (WK, PG) independently assessed the risk of bias of included studies using the Cochrane tool (Higgins 2011a). We resolved disagreements by consensus. We contacted the authors of included studies to request additional information when required. We assessed seven methodological domains: random sequence generation, allocation concealment, blinding of participants, blinding of outcome assessment, incomplete outcome data, selective outcome reporting and other sources of bias (e.g. baseline comparability). For each study, we judged each domain as having 'low', 'high' or 'unclear' risk of bias, with the latter indicating lack of information or uncertainty over the potential for bias. See Table 2 for the detailed criteria we used in our assessment. We considered the blinding of outcome assessment to be at high risk of bias in all studies as the presence or absence of the sealant would reveal the intervention.

Table 2. Criteria for 'Risk of bias' assessment

Random sequence generation (selection bias)	Was the method used to generate the allocation sequence appropriate to produce comparable groups?	We graded this domain to 'low' risk of bias if study authors described a random component in the sequence generation process (e.g. random number table, coin tossing, drawing of lots). If information about the random sequence generation process was not provided or was insufficient, we graded this domain to 'unclear' risk.
Allocation concealment (selection bias)	Was the method used to conceal the allocation sequence appropriate to prevent the allocation from being known in advance of, or during, enrolment?	We graded this domain to 'low' risk of bias if study authors described adequate concealment (e.g. by means of central randomisation, or sequentially numbered, opaque and sealed envelopes) and to 'high' risk of bias if inadequate concealment was documented (e.g. alternation, use of case record numbers, date of birth or day of the week) or if allocation concealment was not used. If insufficient or no information on allocation concealment was provided, the judgement was graded 'unclear' risk.
Blinding (performance bias)	Performance bias is looked at differently for the parallel‐group and split‐mouth studies.	Due to characteristics of each intervention, both participants and personnel are aware which of the 2 active preventive treatments has been applied. For parallel‐group studies, it was not possible to ensure that both groups followed a similar oral hygiene routine. The risk of bias was high. However, for the split‐mouth studies it is unlikely that the children undertook different oral hygiene practices in different areas of the mouth so performance bias was assumed to be of low risk.
Blinding of outcome assessment (detection bias)	Were outcome assessors blinded to the intervention a participant had received?	As sealant materials are visible, blinding of the outcome assessor is possible only if a sealant has been lost. Thus, outcome measurement is related to sealant retention and blinding of outcome assessor is usually impossible. However, it is difficult to assess how likely (or unlikely) it is that the outcome measurement is influenced by lack of blinding of outcome assessors in preventive sealant studies. Although the outcome assessors could not be blinded, the potential for bias could not be ignored. We decided to grade this domain as having 'low' risk of bias if study authors stated that the outcome assessor was not involved in the study design, and as having 'unclear' risk of bias if the study simply reported blinded outcome assessment or if blinding was indicated (e.g. examinations performed independently of previous records, outcome assessors not involved in applying treatments). If a trial reported nothing about blinding of outcome measurement, our judgement was 'high' risk of bias in this domain.
Incomplete outcome data (attrition bias)	How complete were the outcome data for primary caries outcomes? Were dropout rates and reasons for withdrawals reported? Were missing data imputed appropriately?	In caries prevention studies, follow‐up times can last several years. Studies with long follow‐up have the problem of high dropout rates causing uncertainty about data. We decided to base the judgement of this domain on caries efficacy outcome at 24 or 36 months (commonly used follow‐up times in sealant studies). When both follow‐up times were reported, we based our judgement on 24 months. If either of these 2 follow‐up times was not reported, we based our judgement on the first caries efficacy outcome reported in the study (which in this review should be ≥ 1 year). The risk of bias was assessed separately and was reported in the 'Risk of bias' table for caries outcomes for all reported follow‐up times. These assessments were taken into account in the overall risk of bias assessment for caries outcomes within a study. We decided to grade this domain as having 'low' risk of bias if the total proportion of missing outcome data was marginal (< 5%); or if the proportion of missing outcome data was < 25% regardless of the follow‐up time and groups (in parallel‐group studies) were balanced in numbers for missing data; or if missing data had been imputed using appropriate methods. If no information on reasons for dropout across intervention groups was provided, or if the proportion of missing data was documented as total proportion (5–25%), not by group in parallel‐group studies, our judgement was 'unclear' risk. Classifying missing data > 25% as having 'high' risk of bias in all study designs was a pragmatic approach to this domain to make the judgement uniform and transparent. If several teeth were sealed in a child's mouth (a child is a cluster), missing outcome data had to be stated (or counted) at child level (not at tooth level).
Selective reporting (reporting bias)	Were appropriate outcomes reported and were key outcomes missing?	To be included in this review, caries outcomes had to be reported. However, studies could report the outcome in different ways, e.g. incidence of dentinal carious lesion on treated occlusal surfaces of molars or premolars (yes or no); changes in mean figures of decayed, missing and filled surfaces (DMFS); or progression of caries lesion into enamel or dentine. In this review, selective outcome reporting was graded as 'low' risk of bias if the study's prespecified caries outcomes had been reported in the prespecified way.
Other sources of bias	This domain included information on comparability of intervention and control groups, and possible use of co‐interventions by group	Comparability of groups We decided to base our judgement of comparability of groups on baseline information given to groups available at follow‐up times because if only information provided at the start of the study is available, it is impossible to assess whether groups are balanced with each other after follow‐up time as well. The comparability of groups after follow‐up is especially problematic when small studies include children with several teeth and the dropout rate is high, even if dropouts are balanced in numbers and reasons between groups. If no information on the groups was available at follow‐up time, we decided that if the dropout rate (regardless of follow‐up time) was < 25% and dropouts were balanced in numbers and reasons by group, our judgement would be based on information given for groups at the start of the study. We decided to grade this domain as having 'low' risk of bias if groups were balanced in demographic characteristics (such as sex, age and social class) and in baseline caries risk level, or if possible imbalance of groups at baseline or after follow‐up (or both) had been taken adequately into account in the analyses. If baseline characteristics in parallel‐group studies were not given to groups available at follow‐up and the dropout rate was > 25%, we graded the study as having 'unclear' risk. Co‐interventions We decided to grade this domain as having 'low' risk of bias if groups were balanced in number and quality of co‐interventions, or if no co‐interventions were included in the protocol, and as having 'high' risk of bias if groups received different numbers or quality of co‐interventions during the trial. If no information was provided on co‐interventions, our judgement was 'unclear' risk.

Summary assessments of 'Risk of bias'

To draw conclusions about the overall risk of bias for caries outcomes within a study, we classified the studies into three categories: studies with low, unclear or high risk of bias. We determined caries outcomes from data of the included studies (all caries data were extracted at preselected times – annually, at one, two, three, four, five years, etc.).

Our classification was based on the seven domains that we deemed most fundamental in assessing risk of study bias: random sequence generation, allocation concealment, blinding of participants, blinding of outcome assessment, incomplete outcome data, selective outcome reporting and other sources of bias .

We assessed performance bias as at high risk of bias for the parallel‐group studies, but not for the split‐mouth studies. In relation to blinding of outcome assessment, we considered this to be at high risk of bias in all of the included studies as we strongly believe that blinding cannot be achieved with these interventions because the examiner will see the sealant on the occlusal surfaces of the included teeth unless it has been lost.

We defined overall risk of bias categories as follows; however, all studies will be deemed as at high risk of bias due to the unavoidable presence of detection bias.

Low risk of bias (plausible bias unlikely to seriously alter results) if all domains defined above were graded as low risk of bias.
Unclear risk of bias (plausible bias that raises some doubt about results) if all of the domains were graded as low or unclear risk of bias.
High risk of bias (plausible bias that seriously weakens confidence in the results) if one or more domains were graded as high risk of bias.

Measures of treatment effect

We calculated odds ratios (ORs) for differences in sealant and fluoride varnish groups as to whether occlusal surfaces were carious, along with appropriate standard errors and 95% confidence intervals (CIs), using Review Manager 2014. For split‐mouth studies, we calculated ORs using the Becker‐Balagtas method (BB OR) outlined in Curtin 2002. We chose the Becker‐Balagtas method because we intended to pool data from split‐mouth studies and parallel‐group studies in the same meta‐analyses, and the Becker‐Balagtas method facilitates this data synthesis (as outlined by Stedman 2011). The split‐mouth studies included in the review presented paired data by tooth pairs, and the intracluster correlation coefficient (ICC) (needed for BB OR calculations) could be calculated from paired data. If we had included split‐mouth studies presenting data only in marginals (as parallel‐group studies, not as cross‐classification), we would have chosen the conservative ICC of 0.5, and in parallel‐group studies, an ICC of 0. The authors of a cluster‐randomised study provided risk ratio (RR) values that took the clustering into account, and as this was the best estimate, we used these values for the four‐year and nine‐year data for this study (Bravo 2005).

For continuous outcomes and data, we used means and standard deviations (SD) to obtain mean differences (MDs) and 95% CIs.

Unit of analysis issues

In parallel‐group studies and cluster‐randomised studies, we chose the individual to be the unit of analysis.

In split‐mouth studies, we chose the tooth pair within an individual to be the unit of analysis. In some studies, more than one pair of tooth surfaces per child might be treated. These pairs are not independent and should be analysed as 'paired data' on a per‐child basis. However, we were unable to do this from the data presented in these studies. This means that CIs are slightly narrower than they should be, and this was taken into consideration when we interpreted the results.

Dealing with missing data

We contacted trial authors to retrieve missing data when necessary or feasible. We performed analyses using an available‐case data analysis approach, as described in the Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (Higgins 2011b). This approach for calculating response rates uses as a denominator the total number of participants for whom data were recorded for the outcome in question.

In caries‐prevention studies, follow‐up times can be several years. Studies with long follow‐up have the problem of high dropout rates, causing uncertainty in the data. The identified reasons for dropout in the included studies were that children moved away from the study area, moving from the town/city or school change. In Chestnutt 2017, one dropout was because parents decided to not continue in the trial without giving any reason. We decided to include, in the analyses, data from all studies (regardless of dropout rates). We assessed studies with a high dropout rate (i.e. greater than 25% regardless of follow‐up time) to be at high risk of bias. We had intended to evaluate in the sensitivity analyses the effect of risk of bias judgement on study results.

Assessment of heterogeneity

If a sufficient number of studies had been included in any meta‐analyses, we would have assessed clinical heterogeneity by examining the characteristics of studies and the similarity between types of participants (especially baseline caries prevalence levels), interventions and outcomes as specified in the criteria for included studies.

We assessed the significance of discrepancies in estimates of treatment effects from various studies using Cochrane's test for heterogeneity and the I² statistic. The I² statistic describes the percentage of variability in effect estimates that is due to heterogeneity rather than to sampling error. A value greater than 50% may represent substantial heterogeneity (Higgins 2003).

Assessment of reporting biases

If sufficient numbers of trials had been included in any meta‐analysis, we would have assessed the risk of publication bias according to the recommendations on testing for funnel plot asymmetry provided in the Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (Sterne 2011). If asymmetry had been identified, we would have examined possible causes.

Data synthesis

We grouped and analysed studies on the basis of sealant material type (resin‐based sealant and glass ionomer‐based sealant: glass ionomer and resin‐modified glass ionomer) and follow‐up period (short term (up to 12 months); medium term (from 12 months to three years); long term (more than four years). We conducted meta‐analyses in Review Manager 2014, using the generic inverse variance method. In meta‐analyses that included two or three studies, we planned to use the fixed‐effect model, and in meta‐analyses with four or more studies, we planned to use the random‐effects model. We planned to pool data from studies in each comparison regardless of the risk of bias classification of these studies.

When feasible, we pooled in the same meta‐analysis ORs from parallel‐group studies and from split‐mouth studies by using BB ORs in split‐mouth studies, as outlined in the article by Stedman 2011.

Subgroup analysis and investigation of heterogeneity

If a sufficient number of studies had been included in any meta‐analyses, we would have examined the relative effectiveness of sealants and fluoride varnishes at different caries prevalence levels. As data were insufficient, it was not possible to create subgroups for further analyses.

Sensitivity analysis

If a sufficient number of studies had been included in any meta‐analyses, we would have undertaken sensitivity analyses to assess the robustness of results (for caries outcomes) by excluding studies with unclear or high risk of overall bias.

Summary of findings and assessment of the certainty of the evidence

We generated 'Summary of findings' tables, in which we planned to present data related to the occurrence of new dentine carious lesions on occlusal surfaces of permanent molars and data related to any adverse event. No adverse event was reported as a result of applying FV, FS or both of them together. We followed GRADE methods (GRADE 2004) and used GRADEpro GDT software to provide overall grading of the certainty of evidence for caries outcomes for the following comparisons: resin‐based sealant versus fluoride varnish (summary of findings Table 1); glass ionomer or resin‐modified glass ionomer sealant versus fluoride varnish (summary of findings Table 2); and resin‐based sealant plus fluoride varnish versus fluoride varnish alone (summary of findings Table 3). We assessed the certainty of the body of evidence with reference to overall risk of bias of included studies at each outcome, directness of evidence, consistency of results, precision of estimates and risk of publication bias.

Incorporating economic evidence

We have provided a "brief economic commentary" (BEC) to incorporate an economic perspective into the review. The methodology for the BEC follows that described in Chapter 20 of the Cochrane Handbook for Systematic Reviews of Interventions version 6.0 (Shemilt 2019). The aim was to summarise the availability and principal findings of trial‐ and model‐based full economic evaluations (defined as a comparative assessment of costs and outcomes within a cost‐effectiveness, cost‐utility or cost‐benefit analysis framework.

Full economic evaluations that compared fissure sealants with fluoride varnish or fissure sealant plus fluoride varnish compared to fluoride varnish alone in children or adolescents up to age 20 years with at least one permanent molar were included for the BEC. The BEC focuses on the principal findings of the eligible economic evaluations and discusses the likely implications regarding whether the considered preventive approaches are likely to be cost‐effective, and if so, which approaches offer the best value for money from a health system, patient and societal perspective.

An initial search of PubMed was conducted to identify cost‐of‐illness studies describing, measuring and valuing the total resources used in the management of the most common oral diseases, with a focus on data reported for children and adolescents. The results of this search were used to inform the Background section of the review. A supplementary search strategy was conducted to identify relevant health economic evaluations to inform the BEC. The search process to identify full economic evaluation studies included a search of NHSEED up until March 2015 and a supplementary search of MEDLINE (1946 to March 2020) and Embase (1980 to March 2020) using the Scottish Intercollegiate Guideline Network filters for identifying economic studies. The full search strategy for the identification of economic evidence is available in Appendix 6.

The review author who is a health economist (DB) screened the articles and extracted basic data on study characteristics, including the analytical framework (trial‐ or model‐based analysis), type of economic valuation (cost‐effectiveness, cost‐utility, cost‐benefit analysis), analytical perspectives, time horizon, setting, main cost items (including currency and price year). He also extracted the principal findings of analyses including verbatim text on conclusions drawn by authors and text that summarised any uncertainty surrounding the authors’ principal conclusions (in the form of the results of any sensitivity analyses conducted).

We did not critically appraise any identified economic evaluations. The BEC is simply intended to focus on the extent to which principal findings of eligible economic evaluations indicated that different preventive interventions might be judged favourably (or unfavourably) over others from an economic perspective. A narrative summary of the findings of the BEC are provided in the Effects of interventions section of the review.

Results

Description of studies

Results of the search

From the database searches for this update, we identified 141 records after duplicates were removed. We identified two other potential studies. We rejected 106 records after reading the title or abstract, and we obtained the full text of 37 reports to assess eligibility for inclusion, contacting authors if additional information was required. We translated all non‐English language reports for study assessment. Review authors could read reports in English, German and Scandinavian. For this update, we consulted translators to identify and assess the non‐English reports that had potential for inclusion: Dutch (Vermaire 2015) and Chinese (Liu 2014) studies, which were excluded, and another Chinese study, which was included (Tang 2014).

Of the 37 full‐text reports, we excluded 20 because they had ineligible study design, participant population or setting (see Characteristics of excluded studies tables), and 14 were ongoing studies (see Characteristics of ongoing studies table). We identified three new studies for inclusion (Chestnutt 2017; Kalnina 2016; Tang 2014). We brought forward eight studies from the previous version, bringing the total number of included studies to 11 (15 references). See Figure 1.

Figure 1

Study flow diagram.

The search for cost‐effectiveness studies retrieved 87 references, 38 remained after the removal of duplicates.

Included studies

This update includes 11 studies (Bravo 2005; Chestnutt 2017; Florio 2001; Ji 2007; Kalnina 2016; Liu 2012; Raadal 1984; Salem 2014; Splieth 2001; Tagliaferro 2011; Tang 2014).

The 11 included studies evaluated the relative effectiveness of fissure sealants (resin based or glass ionomer) compared with fluoride varnishes, or fissure sealants plus fluoride varnishes compared with fluoride varnishes alone, for preventing dental caries in the occlusal surfaces of permanent molars and premolars of children and adolescents. Dentinal caries means caries of a level of severity that would require intervention with restorative treatment.

Comparisons

Pit and fissure sealants versus fluoride varnishes: resin‐based fissure sealant versus fluoride varnish (seven studies) (Bravo 2005; Chestnutt 2017; Kalnina 2016; Liu 2012; Raadal 1984; Salem 2014; Tang 2014).
Glass ionomer fissure sealant versus fluoride varnish (one study) (Ji 2007); and resin‐modified glass ionomer fissure sealant versus fluoride varnish (two studies) (Florio 2001; Tagliaferro 2011).
- Tagliaferro 2011 actually evaluated whether additional benefit is derived by using sealants and fluoride varnish among children receiving regular oral health education (the evaluation was carried out separately in populations with high risk and low risk of caries).
Pit and fissure sealant plus fluoride varnish versus fluoride varnish alone: resin‐based fissure sealant plus fluoride varnish versus fluoride varnish alone (one study) (Splieth 2001).

Study designs

Six of the 11 studies were of parallel‐group design (Chestnutt 2017; Florio 2001; Ji 2007; Kalnina 2016; Liu 2012; Tagliaferro 2011), two were split‐mouth studies, in which the two interventions (fissure sealant versus fluoride varnish (Raadal 1984) and fissure sealant plus fluoride varnish versus fluoride varnish alone (Splieth 2001)) were randomly allocated to teeth within a tooth pair. The studies by Bravo 2005, Salem 2014 and Tang 2014 were cluster‐randomised trials, the cluster being the school class. Details of studies are summarised in the Characteristics of included studies table.

Settings

Two studies were conducted in Brazil (Florio 2001; Tagliaferro 2011), three in China (Ji 2007; Liu 2012; Tang 2014), one in Germany (Splieth 2001), one in Iran (Salem 2014), one in Latvia (Kalnina 2016), one in Norway (Raadal 1984), one in Spain (Bravo 2005), and one in the UK (Chestnutt 2017). In 10 studies, children were recruited from public dental clinics or schools, and in the other study, children were enrolled from a private dental practice (Splieth 2001). The age range of the children in the studies was five to 10 years.

Interventions

In 10 studies, sealants and fluoride varnishes were applied to occlusal surfaces of permanent first molars. In one study, sealants and fluoride varnishes were applied to occlusal surfaces of premolars (Kalnina 2016); however, this study did not contribute data to our analyses as caries outcomes were zero in both groups at 12 months. Applications were done on sound surfaces (Bravo 2005; Ji 2007; Kalnina 2016; Salem 2014; Tagliaferro 2011), on surfaces with enamel lesions (Florio 2001), or in the same study on sound surfaces or on surfaces with enamel lesions (Chestnutt 2017; Liu 2012; Raadal 1984; Splieth 2001). In Raadal 1984, surfaces with initial caries in enamel to be sealed were prepared mechanically and caries removed before sealant was applied. In Tang 2014, sealants were applied for the permanent premolars or molars and sealant used only on sound surfaces or on enamel lesions (if scored using the ICDAS II scale, codes 0, 1, 2 and 3 are accepted); surface should not be sealed before.

The sealant material in Ji 2007 was glass ionomer; Florio 2001 and Tagliaferro 2011 used resin‐modified glass ionomer; and the other seven studies used resin‐based sealant materials: light‐polymerised resin sealant (Bravo 2005; Chestnutt 2017; Salem 2014; Splieth 2001; Tang 2014), light‐polymerised resin sealant with fluoride (Kalnina 2016; Liu 2012), and autopolymerised resin sealant (Raadal 1984). Five studies reported reapplication of sealants: Bravo 2005 reapplied sealants if partial or total loss had occurred since the previous examination after six, 12, 18, 24 and 36 months; Salem 2014 repaired or reapplied partially and completely lost sealants once if needed after six months; Splieth 2001 examined children semi‐annually for two years, and resealed sealants if necessary; Chestnutt 2017 examined the sealants six, 12, 18, 24 and 36 months, and reapplied if the existing sealant had become detached; and Kalnina 2016 resealed surfaces after six months if necessary.

Complete retention of resin‐based sealants after three years was 74.5% in maxillary molars and 91.4% in mandibular molars (Chestnutt 2017); after two years, complete retention of resin‐based sealants varied from 43% (Salem 2014) to 81% (Splieth 2001). Bravo 2005, with longer follow‐up time, reported complete resin sealant retention of 63% after four years and 39% after nine years. Retention of glass ionomer sealants was fairly high (66% complete retention after one year (Florio 2001 with resin‐modified glass ionomer); 84% after two years (Tagliaferro 2011 with resin‐modified glass ionomer); and 61% after three years (Ji 2007 with chemically cured glass ionomer)).

The fluoride varnishes used were: Durafluor 5% sodium fluoride (Medicom Worldwide Inc., Morrisville, PA, USA) (Salem 2014); Fluor Protector S (0.1%, or 1000 ppm fluoride) (Ivoclar Vivadent Inc., Amherst, NY, USA) (Ji 2007); Fluocal solute (Septodont, France) (Kalnina 2016); and Duraphat (5% sodium fluoride) (Colgate Oral Pharmaceuticals, New York, NY, USA) in the other seven studies. Eight studies applied fluoride varnish biannually to teeth of children in the varnish groups (Chestnutt 2017; Florio 2001; Ji 2007; Kalnina 2016; Liu 2012; Raadal 1984; Salem 2014; Tagliaferro 2011), and one study biannually to all teeth (Splieth 2001). Bravo 2005 applied Duraphat to newly erupted molars and reapplied it to all molars that had remained healthy after six, 12, 18, 24, 30, 36 and 42 months.

Co‐interventions

Six studies included other interventions in combination with the sealants and varnish. In Florio 2001, tap water was fluoridated and all children received professional prophylaxis during dental examination visits. In Raadal 1984, participants followed a fluoride rinsing programme at schools during follow‐up, and use of fluoride tablets was recommended. Splieth 2001 reported that 5% of children used fluoride tablets during the trial; however, it was not clear which participants were involved. Six studies reported motivation and instruction of participants towards good oral hygiene and use of fluoridated toothpaste (Florio 2001; Liu 2012; Raadal 1984; Salem 2014; Splieth 2001; Tagliaferro 2011).

Participants

Age and sex

The studies randomised 3374 children aged five to 10 years to sealant or varnish groups, and evaluated 2553 children. All studies included both boys and girls.

Caries prevalence at baseline

All studies except Ji 2007 and Salem 2014 stated the baseline caries prevalence of the study population. The only study from the 1980s stated that initial mean decayed, missing, filled deciduous teeth (dmft) was 4.7 (SD 3.3) (Raadal 1984).

The three studies conducted in the 1990s stated baseline caries prevalence as follows: in Florio 2001, mean dmfs in the sealant group was 3.8 (SD 2.5), and in the fluoride varnish group 4.5 (SD 2.7); and in Splieth 2001, initial mean DMFS was 0.2. In Bravo 2005, baseline mean decayed, filled deciduous teeth (dft) in the sealant group was 2.2 (SD 2.6), and in the varnish group 2.4 (SD 3.3).

The five studies from the 2010s stated baseline caries prevalences as follows: in Tagliaferro 2011, the baseline mean DMFT index was 4.51 (SD 2.81) for the HRS group (high‐caries‐risk children receiving sealants) and 4.28 (SD 2.54) for the HRV group (high‐caries‐risk children receiving fluoride varnishes), and in low‐caries‐risk groups, dmft plus DMFT was zero. In Liu 2012, baseline mean dmft in the sealant group was 3.19 (SD 2.68) and in the varnish group 3.58 (SD 2.25) for children eight to 10 years of age. In Tang 2014, the baseline mean DMFT index for seven‐ to eight‐year‐old children was 0.08. In Kalnina 2016, the baseline mean DMFT index for 10‐year‐old school children was 1.97. In Chestnutt 2017, the baseline mean DMFT index for six‐ to seven‐year‐old children was 3.2.

Dietary habits

Four studies gave information on diet (e.g. snacking habits of children). In Splieth 2001, during the trial, the mean frequency of cariogenic food intake per day was 15%, including a large number of sweetened drinks. In Liu 2012, at study baseline, 13% of children in the sealant group and 31% in the fluoride varnish group frequently consumed snacks twice a day or more (no information was provided on snacking habits during the trial). In Kalnina 2016, at study baseline, about 90% of children in both groups consumed snacks (with a mean of 2.06 times in sealant group and of 2.6 times in varnish group). Chestnutt 2017 distributed a questionnaire to the participants' parents and used it to collect information about dietary intake and habit, fluoride exposure and dental attendance. At baseline, about 60% of participants who responded to the questionnaire showed that children consumed a cariogenic diet (e.g. chocolate and sweets) between never and four to six times per week, with no significant differences between comparison groups. Throughout the study, there were no significant differences between intervention groups related to diet or other oral health‐related habits.

Outcome measures

An overview of the outcomes reported in each study is given in Table 3.

See: Summary of findings 1 Resin‐based fissure sealant compared with fluoride varnish for preventing dental caries; Summary of findings 2 Glass ionomer fissure sealant or resin‐modified glass ionomer fissure sealant compared with fluoride varnish for preventing dental caries; Summary of findings 3 Resin‐based fissure sealant plus fluoride varnish versus fluoride varnish alone for preventing dental caries

Table 3. Outcomes for each study

Study	New caries lesion (yes/no)	Changes in caries from baseline DMFS on occlusal surfaces	Changes in caries from baseline DMFS on all surfaces	Changes in caries from baseline DMFT on all teeth	Progression of enamel carious lesions into dentine on treated occlusal surfaces	Time taken to apply intervention	Number of visits to repair sealant or apply varnish	Adverse events
Bravo 2005	Yes at 2, 4, 9 years	—	—	—	—	—	Yes, over 4 years	Yes, over 4 years
Chestnutt 2017	Yes, at 3 years	—	—	—	—	—	—	Yes, over 3 years
Florio 2001	Yes, at 1 year	—	—	—	Yes, at 1 year	—	—	—
Ji 2007	Yes, at 3 years	—	—	—	—	—	—	—
Kalnina 2016	Yes, at 1 year but unable to use as 0 in both groups	—	—	—	—	—	—	Yes, over 1 year
Liu 2012	Yes, at 2 years	—	—	—	—	—	—	Yes, over 2 years
Raadal 1984	Yes, at 2 years	—	—	—	—	—	—	—
Salem 2014	Yes, at 2 years but unable to use data	—	—	—	—	—	—	—
Splieth 2001	Yes, at 2 years	—	Yes	—	—	Yes, over 2 years	—	Yes, over 2 years
Tagliaferro 2011	—	Yes, at 2 years	—	—	—	—	—	—
Tang 2014	—	—	Yes, at 2 years	Yes, at 2 years	—	—	—	—

DMFS: decayed, missing and filled permanent surfaces; DMFT: decayed, missing and filled permanent teeth.

Ten studies reported the incidence of dentinal carious lesions on treated occlusal surfaces of first permanent molars in dichotomous form (yes/no). Tagliaferro 2011 reported data in continuous form as mean DMF increments. All studies used visual‐tactile caries diagnostic methods; In addition to visual‐tactile methods, some of the studies used additional methods to assess the caries progression. One study reported the endoscopic examination to be used (Florio 2001); and three studies reported X‐rays: digital X‐rays (Florio 2001), traditional X‐rays (Raadal 1984), and bitewing X‐rays were taken at baseline and after 12 months (Kalnina 2016). Salem 2014 reported caries incidences using two visual‐tactile measures: the WHO criteria (DMF) (WHO 1997) and Nyvad criteria (Nyvad 1999).

Other outcomes reported were caries progression rate (Florio 2001), changes in DMF scores on a whole‐mouth level (Splieth 2001), mean treatment time for sealing and varnish application (Splieth 2001), and mean DMFS (Tang 2014). Five studies considered adverse events (Bravo 2005; Chestnutt 2017; Kalnina 2016; Liu 2012; Tagliaferro 2011). The reported secondary outcomes in Florio 2001 were the number of permanent first molars remaining free of dentinal caries per child for those molars included in the trial; the caries status of treated or untreated caries on each surface of each first molar and the binary outcome of caries occurrence on occlusal versus non‐occlusal surfaces of each included first molar.

Details of all outcomes reported for each study are given in the Characteristics of included studies table.

Five studies stated intra‐examiner and inter‐examiner agreement for caries diagnosis: Liu 2012 reported the Kappa coefficient for intra‐examiner reliability to be over 0.9, Tagliaferro 2011 over 0.90, Salem 2014 about 0.8, and Bravo 2005 greater than 0.68. In Chestnutt 2017, inter‐ and intra‐examiner reproducibility were both high, with mean kappa scores of 0.82 for inter‐examiner and 0.89 for intra‐examiner.

Funding source

Six studies were supported by governmental or academic sources or by independent research foundations (Bravo 2005; Chestnutt 2017; Florio 2001; Liu 2012; Salem 2014; Tagliaferro 2011). The other five studies provided no information on funding.

Excluded studies

We excluded 20 for reasons presented in the Characteristics of excluded studies table. Reasons for exclusion varied, and for some studies, we identified several reasons for exclusion. The main reasons were: no randomisation or no mention of randomisation; not comparing sealant with fluoride varnish and flaws in outcome data.

Risk of bias in included studies

We contacted the authors of seven studies to request additional information for assessment of risk of bias, as information in the report was insufficient to permit final decisions (Bravo 2005; Florio 2001; Liu 2012; Raadal 1984; Salem 2014; Splieth 2001; Tagliaferro 2011). The studies by Ji 2007 and Tang 2014 were translated and data extracted by translators. 'Risk of bias' assessments for each individual study are presented in the 'Risk of bias' tables included under Characteristics of included studies, and results are presented graphically by domain over all studies (Figure 2) and by individual study (Figure 3).

Figure 2

'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

Figure 3

'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.

Allocation

Random sequence generation was adequate, indicating low risk of bias in eight studies (72%) (Chestnutt 2017; Florio 2001; Liu 2012; Raadal 1984; Salem 2014; Splieth 2001; Tagliaferro 2011; Tang 2014). Random sequence was generated most often by using random numbers or tossing coins. We assessed one study at high risk of bias (Bravo 2005), and two at unclear risk of bias (Ji 2007; Kalnina 2016).

We graded allocation concealment at low risk of bias in six studies (Chestnutt 2017; Liu 2012; Raadal 1984; Salem 2014; Splieth 2001; Tagliaferro 2011). In four studies, allocation concealment was unclear (Florio 2001: Ji 2007; Kalnina 2016; Tang 2014), and in one study, it was at high risk of bias (Bravo 2005).

Blinding

Performance bias is possible in parallel trials (see Table 2) because personnel and participants are likely to know which of the two active preventive treatments a child is given, though it could be argued it is unlikely to affect dental behaviour of a child during the trial, especially when follow‐up is long (one or more years in this review). In split‐mouth trials, performance bias less of a risk as participants are very unlikely to perform oral hygiene differently in different parts of the mouth (Raadal 1984; Splieth 2001).

We assessed blinding of outcome measurement/assessment as high in all studies as the presence or absence of the sealant reveals if it has been used, assuming it has not been lost.

Incomplete outcome data

Two studies had follow‐up of 12 months: we assessed them at high risk of bias because dropout rates were unevenly distributed between study groups (Florio 2001; Kalnina 2016). The studies providing data at 24 months of follow‐up were at low risk of attrition bias (Ji 2007; Liu 2012; Raadal 1984; Salem 2014; Splieth 2001; Tagliaferro 2011; Tang 2014). The two studies providing data at 36 months of follow‐up were at low risk of bias in this domain (Chestnutt 2017; Ji 2007). The only study providing data at 48 months of follow‐up was at unclear risk of bias because no information on dropouts was provided by study group (there was 18% dropout across the study) (Bravo 2005). Bravo 2005 also measured outcomes at nine years of follow‐up and was at high risk of attrition bias at this time point as the proportion of participants assessed and included in the analysis was only 33%.

Selective reporting

All studies reported their prespecified outcomes adequately so were at low risk of bias.

Other potential sources of bias

Baseline imbalance

We assessed the comparability of study groups and possible co‐interventions during the trial as balanced between study groups in six studies (Bravo 2005; Liu 2012; Raadal 1984; Salem 2014; Splieth 2001; Tagliaferro 2011). Two of the six studies were of split‐mouth design, where conditions are the same for both teeth within a tooth pair (Raadal 1984; Splieth 2001); the other four studies were parallel‐group studies (Bravo 2005; Liu 2012; Salem 2014; Tagliaferro 2011). There was no information on comparability of study groups in Ji 2007, so our judgement was unclear risk of bias. Study groups in Kalnina 2016 were comparable in terms of age, sex and baseline caries, with no significant differences in caries risk factors (i.e. child's toothbrushing habits, snacking habits and family‐related factors); however, it was assessed as at unclear risk of bias as there was no information about randomisation and concealment 15 participants dropped out. We assessed Florio 2001 at high risk of bias due to imbalance at baseline.

Overall risk of bias

The overall risk of bias was high for all studies due to being unable to blind the interventions when undertaking outcome assessment.

Effects of interventions

We present a summary of main results for the following comparisons: resin‐based sealant versus fluoride varnish (summary of findings Table 1); glass ionomer or resin‐modified glass ionomer fissure sealant versus fluoride varnish (summary of findings Table 2); and resin‐based fissure sealant plus fluoride varnish versus fluoride varnish alone (summary of findings Table 3).

Results from nine studies are incorporated in this review (Bravo 2005; Chestnutt 2017; Florio 2001; Ji 2007; Liu 2012; Raadal 1984; Splieth 2001; Tagliaferro 2011; Tang 2014). Although the study by Salem 2014 met the inclusion criteria, results and data (complex multi‐level model with teeth nested in a child nested in a school class nested in a school) were not provided in useable form. In addition, the study by Kalnina 2016 met the inclusion criteria; however, the caries outcomes for both groups of fissure sealant and fluoride varnish at 12 months were zero so this did not contribute to the analysis. Kalnina 2016 applied interventions to the occlusal surfaces of premolars, but all other studies applied sealants and fluoride varnish to occlusal surfaces of permanent first molars.

Sealant versus fluoride varnish

Primary outcome – occurrence of new dentinal carious lesion on treated occlusal surfaces of molars or premolars

Resin fissure sealant versus fluoride varnish

Five studies compared resin‐based fissure sealant versus fluoride varnish: three reported results at two years (the split‐mouth study by Raadal 1984 and the parallel‐group studies by Liu 2012 and Tang 2014); one parallel‐group study reported results at three years (Chestnutt 2017); and one parallel‐group study reported results at two, four and nine years (Bravo 2005) (see Table 1).

In order to provide a more useful summary estimate of effect (rather than several single estimates of effect), we pooled the data for four studies with follow‐up periods between two and three years. This assumes that the OR, which is a relative measure, does not change over the follow‐up time period of two or three years. This meta‐analysis pooling the effect estimates of Bravo 2005, Chestnutt 2017, Liu 2012, and Raadal 1984, showed that we are uncertain whether resin fissure sealants are better than fluoride varnish in preventing dentinal carious lesions on treated occlusal surfaces of molars or premolars within the period of two to three years after initial treatment (OR 0.67, 95% CI 0.37 to 1.19; 1683 evaluated participants; Analysis 1.1). It should be stressed that these studies assessed odds of caries at different levels – person/child (Chestnutt 2017; Bravo 2005), tooth (Liu 2012), and surfaces (Raadal 1984), which could have affected precision of different estimates. There was high heterogeneity (I² = 84%). We judged the certainty of the evidence to be very low. Tang 2014 found slight benefit of resin‐based sealant with DMFT at two‐year follow‐up (MD 0.08, 95% CI –0.14 to –0.02; 542 participants). The slight benefit that was observed in DMFT seems not to be clinically important on a scale from 0 to 28/32; however, if only existing permanent teeth of a child are taken into account when assessing this index, the difference could be relevant (Analysis 1.4).

Bravo 2005 found a significant difference in favour of visible‐light‐polymerised resin sealant compared with fluoride varnish, with an RR of 0.42 (95% CI 0.21 to 0.84; Analysis 1.2) at four years and 0.48 (95% CI 0.29 to 0.79; Analysis 1.3) at nine years of follow‐up (five years after the four years of active intervention; Analysis 1.3). As expected, dropout rates were high after nine years of follow‐up in Bravo 2005.

Glass ionomer fissure sealant versus fluoride varnish

Three studies evaluated glass ionomer fissure sealant versus fluoride varnish (Florio 2001; Ji 2007; Tagliaferro 2011). We were unable to perform any meta‐analyses and assessed the certainty of the evidence to be very low.

Resin‐modified glass ionomer fissure sealant versus fluoride varnish at one year

One small study, at high risk of bias, provided results for one year of follow‐up (Florio 2001; Table 1). This study found no significant difference between intervention groups at one year of follow‐up (OR 0.18, 95% CI 0.01 to 4.27; Analysis 2.1). All occlusal surfaces under examination had enamel lesions before applications.

Glass ionomer fissure sealant versus fluoride varnish at two years and three years

One study with incomplete information and analyses compared glass ionomer fissure sealant versus fluoride varnish at two years and three years (Ji 2007). In the statistical analyses of this study, clustering of teeth within a child was not taken into account (with adequate standard errors of estimates), and no information on numbers of children at follow‐up times was available for re‐analysis of data. However, because the numbers of decayed teeth were small in both groups, we decided to report the absolute numbers of decayed tooth surfaces in sealant and fluoride varnish groups without effect estimates (ignoring the clustered data). We noted no significant differences in rates of caries development between groups (at 24 months, 11/321 (3.4%) sealed surfaces and 13/320 (4.1%) fluoride‐varnished surfaces were decayed, and at 36 months, 22/311 (7.1%) sealed surfaces and 24/320 (7.5%) fluoride‐varnished surfaces were decayed). The rate of caries in the control group without intervention was 14% (48/348) at 24 months and 21% (71/340) at 36 months.

Resin‐modified glass ionomer cement plus oral health education versus fluoride varnish plus oral health education at two years

One study provided results for comparison of resin‐modified glass ionomer cement plus oral health education every three months versus fluoride varnish application biannually plus oral health education every three months (Tagliaferro 2011). The comparison was performed separately for high‐caries‐risk children and for low‐caries‐risk children. Groups to be compared were HRS (high‐risk children with sealant application plus oral health education) versus HRV (high‐risk children with fluoride varnish application plus oral health education); and LRS (low‐risk children with sealant application plus oral health education) versus LRV (low‐risk children with fluoride varnish application plus oral health education).

Investigators reported results as follows: after 24 months, the HRS group showed significantly smaller caries increments when compared with the HRV group (mean DMF increments on occlusal surfaces of first permanent molars was 0.06 (SD 0.25) in the HRS group and 0.29 (SD 0.68) in the HRV group (MD 0.23, 95% CI 0.02 to 0.44; P = 0.03). For low‐risk groups, there were no statistically significant differences among treatments with mean DMF increment of 0.02 (SD 0.15) for LRS and 0.09 (SD 0.29) for LRV groups (MD 0.07, 95% CI –0.03 to 0.17; P = 0.16). Study authors concluded "that in a 2‐year period, oral health education was sufficient to control occlusal caries in low‐risk children while for high‐risk children, sealant application in addition to oral health education was considered the best strategy."

Heterogeneity

Results of the meta‐analysis of four studies evaluating fissure sealants versus fluoride varnishes at two to three years showed no evidence that one intervention is more effective than another although the result is uncertain (Bravo 2005; Chestnutt 2017; Liu 2012; Raadal 1984). It should be noted that the superiority of sealants noted in the Norwegian split‐mouth study by Raadal 1984 may have been influenced by the carry‐over effect of fluoride varnish, even though this is unlikely due to a fast‐setting base and a small amount of fluoride varnish applied to one or two control teeth. Further, this split‐mouth study provided no information on caries incidence in control teeth without treatment and was conducted in early 1980s. It might be the possibility that the risk of caries was higher in 1980s have influenced the superiority of sealants noted in the Norwegian split‐mouth study by Raadal 1984.

In the British study by Chestnutt 2017, the fissure sealants were placed on sound occlusal surfaces of first permanent molars and reapplied when partially or totally lost during the 36 months of follow‐up, whereas the fluoride varnish was applied biannually. The sealant retention at 36 months was reported as 74.5% in maxillary first permanent molars and 91.4% in mandibular first permanent molars. The proportion of children who developed dentine caries dmft on at least one molar at 36 months was generally similar in both intervention arms (19.6% the fissure sealant arm and 17.5% in the fluoride varnish arm).

In the Chinese study conducted by Liu 2012, numbers of decayed tooth surfaces in all groups were small (at 24 months of follow‐up, proportions of pit/fissure sites with dentine caries in the sealant group was 1.6%, fluoride varnish group 2.4% and control group 4.6%). In Liu 2012, the low incidence of fissure caries in the control group without treatment may be explained in part by today's slower dental caries progression rate (Frencken 2017).

Two studies included surfaces with enamel caries lesions, in addition to sound surfaces (Liu 2012; Raadal 1984). Raadal 1984 opened surfaces with enamel lesions mechanically before sealant application, but researchers provided no information on the number of such surfaces included. In the study by Liu 2012, 35% of tooth sites had early‐stage caries at baseline. In the study by Raadal 1984, retention of sealants after 23 months of follow‐up was better (63%) than in the study by Liu 2012, which reported 46% retention of sealants. Both studies reported prevalence of caries in primary teeth at baseline, and it was slightly lower in Liu 2012 (baseline mean dmft 3.19 (SD 2.68) in sealant group and 3.58 (2.25) in fluoride varnish group). In Raadal 1984, the mean dmft was 4.7 (SD 3.3).

The Spanish study by Bravo 2005 (started in 1990), which placed sealants on sound surfaces and reapplied them when partially or totally lost during the four‐year active preventive programme, found resin sealants better than fluoride varnishes at four years and nine years of follow‐up. Complete sealant retention was 63% at four years and 39% at nine years. The incidence of caries in the control group after nine years was 77% on occlusal surfaces, whereas 26.6% of sealant teeth and 55.8% of fluoride‐varnished teeth had developed caries at nine years. Caries prevalence among primary teeth at baseline was stated as mean dmft in the sealant group 2.24 (SD 2.59) and in the fluoride varnish group 2.42 (SD 3.26). The total dropout rate of Bravo 2005 at nine years of follow‐up was high (67%), undermining the reliability of results.

The Chinese study by Tang 2014 applied the fluoride varnish biannually (four times in two years) and placed fissure sealants once on sound occlusal surfaces of first permanent molars. Sealant retention was 90.12% at two years. The increment of dental caries was less in the sealant group (DMFT 0.06 (SD 0.26); DMFS 0.06 (SD 0.26)) compared to the varnish group (DMFT 0.14 (SD 0.44); DMFS 0.15 (SD 0.45)).

Primary outcome – changes from baseline in decayed, missing and filled figures at surface, tooth and whole‐mouth levels

The studies did not report changes from baseline in DMF figures at surface, tooth and whole‐mouth levels.

Primary outcome – progression of dentinal carious lesions into enamel or dentine

One study, which compared resin‐modified glass ionomer fissure sealant versus fluoride varnish at one year, included at baseline only enamel caries lesions and reported at 12 months whether arrestment of enamel caries lesions or progression into dentine caries with both interventions (Analysis 2.1) (Florio 2001). We are uncertain if the sealant is better than fluoride varnish in preventing the progression of caries on treated surfaces from enamel to dentin as the effect was very imprecise due to small sample size (OR 0.18, 95% CI 0.01 to 4.27).

Secondary outcome – time taken to apply pit and fissure sealant or fluoride varnish

None of the studies measured time taken to apply pit and fissure sealant or fluoride varnish.

Secondary outcome – number of visits to the dentist for repair of sealant or fluoride varnish application

One study directly reported the number of visits for repair or reapplication of sealants or fluoride varnish applications (Bravo 2005). The mean number of treatment visits per child during the active phase of the programme was 2.2 (SD 1.1) (maximum 6) for children in the resin sealant group and 7.3 (SD 1.0) (maximum 8) for children in the varnish group (MD 5.02, 95% CI 4.55 to 5.94; fewer visits in the sealant group). This difference is great because the sealant was reapplied only when partial or total loss occurred, whereas the varnish was systematically reapplied.

Secondary outcome – safety of using sealants and fluoride varnishes assessed by presence or absence of adverse events

Five studies considered adverse events associated with sealants and fluoride varnishes (Bravo 2005; Chestnutt 2017; Kalnina 2016; Liu 2012; Tagliaferro 2011). Participants detected and reported no adverse events.

Sealant plus fluoride varnish versus fluoride varnish alone

One split‐mouth study compared resin‐based fissure sealant plus fluoride varnish versus fluoride varnish alone, and analysed 92 children after two years (Splieth 2001).

Primary outcome – occurrence of new dentinal carious lesions on treated occlusal surfaces of molars or premolars

Investigators found a significant difference in favour of the sealant plus fluoride varnish compared with fluoride varnish alone (OR 0.30, 95% CI 0.17 to 0.55; Analysis 3.1; Table 1). There was a caries increment of 5.5% (9 children) in sealed teeth compared to 17.5% (30 children) in teeth that received fluoride varnish only. This study considered both sound occlusal surfaces and surfaces with enamel lesions. Incomplete blinding of outcome measurement caused some uncertainty in the results, although the study was otherwise well conducted. We assessed the certainty of the evidence as very low because of the risk of detection bias, small number of participants, age of the study (conducted in the 1990s) and lack of information on caries incidence among control teeth without treatment.

Primary outcome – changes from baseline in decayed, missing and filled figures at surface, tooth and whole‐mouth level

Splieth 2001 reported changes in DMF index at the whole‐mouth level during this study. The mean DMFS score of the whole mouth in the study population increased from 0.2 to 0.6 after one year and to 1.1 after two years. Study authors reported that most caries still occurred on occlusal surfaces of first permanent molars (50.9%).

Primary outcome – progression of dentinal carious lesions into enamel or dentine

The study did not report progression of dentinal carious lesions into enamel or dentine.

Secondary outcome – time taken to apply pit and fissure sealant or fluoride varnish

Splieth 2001 reported a mean treatment time for sealing and fluoride varnish application. Total time needed for sealing and resealing of two teeth was on average 29 minutes during two years, of which most of the time was spent on initial sealants (about 17 minutes). Mean treatment time for each fluoride varnish application was under three minutes (total time during intervention: nine minutes; SDs not presented).

Secondary outcome – number of visits to the dentist for repair of sealant or fluoride varnish application

The study did not measure the number of visits to the dentist for repair of sealant or fluoride varnish application.

Secondary outcome – safety of using sealants and fluoride varnishes assessed by presence or absence of adverse events

Splieth 2001 did not measure adverse events, but five other studies in this review that did evaluate sealants and fluoride varnish reported there were no adverse events for either intervention (see 'Sealant versus fluoride varnish').

Brief economic commentary

To supplement the main systematic review of the effectiveness, we sought to identify trial‐ and decision model‐based economic evaluations of pit and fissure sealants compared to fluoride varnish or fissure sealant plus fluoride varnish compared to fluoride varnish alone for children or adolescents in permanent teeth. Our search identified four relevant economic evaluations.

Two studies conducted Markov decision analysis models to assess the cost‐effectiveness of fissure sealant versus fluoride varnish (Chestnutt 2017 in the UK; Khouja 2018 in the USA). Chestnutt 2017 conducted a within‐trial and model‐based (five‐ and 10‐year time horizon) economic evaluation to assess the cost‐effectiveness (cost per 1% proportion of caries into dentine prevented) and cost‐utility (cost per quality‐adjusted life year (QALY)) of resin‐based fissure sealant (checked and replaced as necessary) compared to fluoride varnish (six‐monthly over 30 months). The study was conducted in children aged six and seven years with at least one fully erupted first permanent molar free of caries into dentine, attending mobile dental clinics at primary schools in Wales. A healthcare payer and partial societal (including costs to families) perspective were considered. The within‐trial analysis found that, over three years of follow‐up, fissure sealants were more costly from both an NHS (2015 data: MD GBP 68.13, 95% CI GBP 5.63 to GBP 130.63; P = 0.033) and partial societal (2015 data: MD GBP 71.96, 95% CI GBP 7.21 to GBP 136.71; P = 0.029) perspective. Given the trial demonstrated no differences in effects, or QALYs, the within‐trial analysis found that fluoride varnish was the most likely cost‐effective strategy, with a probability of cost‐effectiveness of 70% at a threshold willingness to pay for a QALY gain of GBP 20,000. The Markov extrapolation model found that fluoride varnish was also less costly and more effective in the longer term, with a probability of cost‐effectiveness in excess of 95% at the same threshold value. Despite some limitations around the short time horizon of the economic model, which the authors explain was due to a lack of robust long‐term data in dentistry, this appears to be a methodologically robust economic evaluation, in the context of the current data availability. The authors appropriately acknowledge that there is a need for future work to develop and improve on preference‐based utility instruments to aid economic evaluation of dental care interventions.

Khouja 2018 conducted a cost‐effectiveness analysis (cost per first carious lesion averted), using a Markov model with nine‐year time horizon, in a USA general dental practice setting, in children with first permanent molars. The study found that, assuming all fissure sealants would be replaced, fissure sealants were less expensive, with cost savings of USD 324.09 per case (2011 data) and more effective (+0.31 additional first cases of caries avoided) compared to fluoride varnish in preventing occlusal dental caries lesions, and were thus deemed likely to be cost‐effective. It is relevant to note, however, that the study considers only the costs of intervention delivery, and does not consider the potential cost savings associated with avoidance of expensive restorative treatment for carious lesions for the more effective intervention. If the underpinning clinical effectiveness data are robust, and based on sound methodology, then the inclusion of downstream treatment costs would likely improve the cost‐effectiveness case for fissure sealants in this scenario.

Two further studies conducted simple calculations of mean cost‐effectiveness ratios in Australian and US settings (Enno 1982 in Australia; Neidell 2016 in the USA). Enno 1982 found that over two years, the ratio of cost savings in terms of caries treatment avoided to intervention delivery costs for preventive care was 2.1:1 (over three years) for fluoride varnish and 0.77:1 (over two years) for fissure sealants. Mean cost‐effectiveness ratios for fluoride varnish were AUD 3.49 (1982 values over three years) per surface saved for fissure sealants and AUD 18.49 (1982 values over two years) per surface saved for fluoride varnish. It should be noted that these mean cost‐effectiveness ratios were based on a naive comparison of effectiveness between two potentially quite heterogeneous studies, with different follow‐up periods, and should thus be interpreted cautiously. Neidell 2016 conducted a simple calculation of the mean cost per 1% caries reduction for fissure sealants (with possibility of re‐application) and fluoride varnish (every six months) over a 3.5‐year time horizon in a USA school‐based setting. The study included only intervention costs, from the healthcare provider perspective and did not consider longer‐term cost implications. The average cost‐effectiveness ratio (ACER) (year not reported) for fissure sealants was USD 136.63, compared to USD 85 to USD 102 across different percentage reduction in caries explored for fluoride varnish. The study concluded that fluoride varnish may be more cost‐effective because fissure sealants are more costly to deliver. However, the author's conclusions require cautious interpretation. The study excluded any longer‐term cost savings associated with treatment of decay avoided as a result of the more clinically effective intervention. The study was conducted over a short time and may not have captured all the costs and benefits of relevance to decision makers (e.g. the full extent of long‐term benefits).

Discussion

Summary of main results

Resin fissure sealants versus fluoride varnishes

The conclusion of this review has now changed with the addition of one new large, good‐quality study (Chestnutt 2017). We are uncertain whether sealants were superior to fluoride varnish (or vice versa) over 36 months of follow‐up. Four studies with follow‐up times of two to three years contributed to a pooled estimate found no differences in effectiveness. There was substantial heterogeneity and we assessed the certainty of the evidence as very low, in contrast to the last published version of the review, which assessed the certainty as low. One study found a slightly greater reduction in caries increment with sealants (Raadal 1984), but this study was conducted more than 30 years ago when caries incidence was higher and progression more rapid. At four and nine years of follow‐up, results from one small study suggested a benefit for sealant, but we considered this limited evidence to be very low certainty (Bravo 2005). Overall, we interpret the current body of evidence to suggest that there may be no difference in effectiveness between resin fissure sealants and fluoride varnish when applied to occlusal surfaces of permanent molars, with both interventions reducing caries incidence. It should also be stressed that Chestnutt 2017 investigated the sample with apparently the lowest risk of caries among four analysed trials while the effect of sealants is more visible in high‐risk populations. In future studies, grouping of studies by baseline risk might give more clear answers. In addition the results of Tang 2014 on DMFT data and Bravo 2005 on RR data, both point toward significant improvement of outcomes by the use of sealants as intervention; however, in the case of Tang 2014 it is probably not clinically important.

Glass ionomers and resin‐modified glass ionomers versus fluoride varnishes

Three studies – one with traditional glass ionomer (Ji 2007) and two with resin‐modified glass ionomer (Florio 2001; Tagliaferro 2011) – compared glass ionomer versus fluoride varnish. Meta‐analysis was not possible. The small study by Florio 2001 analysed 21 participants and reported no differences between resin‐modified glass ionomer sealant and fluoride varnish at one year. Retention of sealant was 66%. In contrast, Tagliaferro 2011 concluded that over a two‐year period, sealant application in addition to oral health education was the best strategy for children at high risk of caries. The retention rate was high (84% after 24 months). In Ji 2007, numbers of decayed teeth were small in both treatment groups, after two years of follow‐up (at 24 months: 3.4% of sealed surfaces and 4% of fluoride‐varnished surfaces were decayed; at 36 months: 7.1% of sealed surfaces and 7.5% of fluoride‐varnished surfaces were decayed). Rates of caries in control group teeth without intervention were 14% at 24 months and 21% at 36 months. Sealant retention was 60% after three years. Again we are uncertain that glass ionomer and resin modified glass ionomer sealants were superior to fluoride varnish.

Sealant plus fluoride varnish versus fluoride varnish alone

The German split‐mouth study found that sealant given concurrently with fluoride varnish was better than fluoride varnish alone at 24 months' follow‐up (Splieth 2001). Children were examined twice a year for two years; sealants were resealed if necessary and fluoride varnish was applied to all teeth at the time of examination (including the sealed tooth). Study authors reported that the study was conducted in a low‐caries‐risk population and that retention rate of the sealants was high (81%). However, the mean frequency of cariogenic food intake per day was reported to be 15, including a large number of sweetened drinks. Oral hygiene was moderate.

Safety of using sealants and fluoride varnishes assessed by presence or absence of adverse events

Five studies assessed or considered adverse events of sealants and fluoride varnishes (Bravo 2005; Chestnutt 2017; Kalnina 2016; Liu 2012; Tagliaferro 2011). Participants did not detect or report any adverse events during or in the 48 hours after treatment in intervention groups and no adverse event were reported during the follow‐up period.

However, some systematic reports have considered the possible oestrogen‐like effects of resin‐based materials including BPA (Azarpazhooh 2008a; Fleisch 2010). This synthetic chemical resin is widely used in the production of plastic products intended for everyday life but are rarely used as such in dental materials (ADA 2003). Dental resins include primarily BPA derivatives (e.g. bisphenol A‐glycidyl methacrylate, bisphenol A dimethacrylate) rather than pure BPA. These derivatives can hydrolyse to BPA and can be detected transiently in saliva (Arenholt‐Bindslev 1999; Schmalz 1999). BPA has been detected in saliva for up to three hours after application of resin sealants (Fleisch 2010). Evidence suggests that patients are not at risk for oestrogen‐like effects when sealants are used (ADA 2003; Azarpazhooh 2008a; Fleisch 2010). The American Dental Association has concluded that estimated BPA exposure from dental materials is recorded as very low compared with total estimated daily BPA exposure from food and environmental sources (ADA 2003).

Brief economic commentary

We did not subject the identified economic evaluations to a formal critical appraisal and we did not attempt to draw any firm or general conclusions regarding the relative costs or efficiency of different preventive programmes. However, evidence collected from economic evaluations with more rigorous methodological quality (i.e. Chestnutt 2017) indicates that fluoride varnish may achieve similar outcomes to fissure sealants, but at lower costs. However, it is noted that this study was conducted in the UK setting and that the findings may not be transferable to other settings or health systems. The BEC notes that other studies, of generally low quality, draw varying conclusions regarding the most cost‐effective preventive strategy. End users of this review will need to assess the extent to which methods and results of the higher quality Chestnutt 2017 evaluation may be applicable (or transferable) to their own setting or country's health system. It is possible that further context‐specific health economic evaluations may be required.

Overall completeness and applicability of evidence

Date

Two studies were undertaken since the last review update in 2016 (Chestnutt 2017; Kalnina 2016). Eight studies were conducted between 2000 and 2014 (including one added in this update, Tang 2014), and one was in the 1980s.

Setting

Most studies recruited children from schools or public‐oriented dental clinics. One study enrolled children from a private dental practice (Splieth 2001). In general, these studies were conducted in well‐equipped dental settings.

Diagnosis

This review compared sealants versus fluoride varnishes for prevention or control of caries, and we accepted studies with sound occlusal surfaces of molars and premolars or with enamel lesions. Seven of the 11 included studies reported applications only on sound surfaces (Bravo 2005; Chestnutt 2017; Ji 2007; Kalnina 2016; Salem 2014; Tagliaferro 2011; Tang 2014); one study only on surfaces with enamel lesions (Florio 2001); and three studies on sound surfaces or on surfaces with enamel lesions (Liu 2012; Raadal 1984; Splieth 2001). In addition to clinical‐tactile caries diagnostic methods, two studies used other diagnostic methods before applications. Liu 2012 used the DIAGNOdent laser fluorescence device (KaVo Dental Corporation, Lake Zurich, IL, USA) to rule out molars with caries in dentine and fissures with potential dentine caries, and Florio 2001 used digital radiographic and endoscopic examinations to evaluate restricted enamel decay lesions.

Caries diagnosis on occlusal surfaces can, however, be challenging. Conventional visual, tactile and radiographic methods in the diagnosis of occlusal caries have not been accurate enough to identify whether a lesion extends into the dentine (McComb 2001). New technologies such as laser fluorescence methods (e.g. DIAGNOdent device) may be sensitive in detecting occlusal dentinal caries (Bader 2004; Twetman 2013), but the likelihood of false‐positive diagnoses may increase when laser fluorescence is used rather than visual methods (Bader 2004). Regardless of the caries diagnostic method used, the condition of an occlusal surface to be sealed or varnished remains in any case somewhat unclear.

Ongoing studies

There are 10 ongoing trials that may contribute to our next update and help clarify our findings.

Quality of the evidence

Resin‐based sealant versus fluoride varnish

We assessed the certainty of the body of evidence for resin‐based pit and fissure sealants compared with fluoride varnishes as very low according to GRADE assessment criteria (summary of findings Table 1). The pooled estimate of four studies found no evidence to conclude that resin sealants or fluoride varnishes were superior at two to three years (OR 0.67, 95% CI 0.37 to 1.19); the studies were well conducted (Bravo 2005; Chestnutt 2017; Liu 2012; Raadal 1984), but incomplete blinding of outcome measurements/assessments may have caused bias in the results. At four and nine years, the only study evaluating this comparison (with high dropout rates) found more caries on fluoride‐varnished occlusal surfaces than on resin‐sealed surfaces (Bravo 2005).

Two of the studies individually showed similar effectiveness between resin sealants and fluoride varnishes. One was conducted in the 2000s; the other was conducted between 2011 and 2013 (Chestnutt 2017). One study did not contribute to the analyses as there was no caries development in either group at 12 months (Kalnina 2016). The two studies favouring sealants were conducted earlier in the 1980s and 1990s. It has been stated that the progression rate of caries in permanent teeth has become slower (Whelton 2004), and varies between populations, making the evidence uncertain, especially when the follow‐up time is fairly short. Effectiveness of resin‐based sealants is strongly related to retention of sealant, and retention also depends on follow‐up time.

Glass ionomer and resin‐modified glass ionomer versus fluoride varnishes

We assessed the certainty of the body of evidence for glass ionomer sealants (one study with original chemically cured material, and two studies with a light curable type modified with resin) compared with fluoride varnishes as very low according to GRADE assessment criteria (summary of findings Table 2). This rating implies that we are very uncertain about the estimates. Although all three studies comparing glass ionomer versus fluoride varnish reported similar results (no differences between interventions), we downgraded the evidence by three levels because of the small number of trials, with different designs and follow‐up times, which were at high or unclear risk of bias. Further, Tagliaferro 2011 evaluated whether additional benefit was derived from sealants and fluoride varnishes among children receiving regular oral health education.

Sealant plus fluoride varnish versus fluoride varnish alone

We assessed the body of evidence comparing resin‐based sealant plus fluoride varnish versus fluoride varnish alone at very low certainty according to GRADE assessment criteria (summary of findings Table 3). We downgraded the certainty of the evidence by three levels because the comparison included one study (92 analysed participants) conducted in the 1990s and there was no information on caries incidence of control teeth without treatment, and, although the study was otherwise well conducted, there was no blinding of outcome measurement.

Potential biases in the review process

Study design

In a split‐mouth design, it could be assumed that varnish applied to control teeth might also impact teeth in the intervention group through saliva. However, Sköld‐Larsson 2000 showed that fluoride varnish application elevated fluoride concentrations of dental plaque locally in the treated teeth quadrant but not in the opposite untreated quadrant. Any carry‐over effect of fluoride varnishes would most probably be dose dependent, and we assessed carry‐over effects on sealed occlusal surfaces to be insignificant because they have a fast‐setting base and only a small amount of fluoride varnish was applied to one or two control teeth. Therefore, we decided to accept split‐mouth studies into this review. We grouped the studies based on the used sealants material. Although sealants will work as physical barrier, they still have different properties based on their materials which presumably may influence their performance and longevity.

Reporting bias

We decided to consider only studies with a full‐text report. We excluded studies reported only as abstracts because evidence has shown discrepancies between data reported in the abstract and provided in the final published full report, and has indicated that information on trial quality indicators is often lacking (Chokkalingam 1998; Hopewell 2006). Thus, we judged that the full‐text report was required to ensure reliable data extraction and assessment of risk of bias. To diminish risk of publication bias, we contacted the authors of potential abstracts to ask whether a full‐text report of the study (unpublished or published) was available.

Agreements and disagreements with other studies or reviews

Neusser 2014 considered fissure sealants versus fluoride varnishes and presented conclusions based on the trials of Bravo 2005, Raadal 1984, and Tagliaferro 2011 (which are also included in this review), and on a previous version of this Cochrane systematic review (Hiiri 2010). The review by Neusser 2014 concluded, "The studies and literature reviews have shown protective effects of pit and fissure sealants compared to the professional application of fluorides, particularly in children and adolescents at high caries risk. However, because of methodological flaws, the results of the RCTs should be interpreted with caution."

Another well‐conducted systematic review was undertaken by Wright 2016 and included three studies at two to three years' follow‐up, one of which was Liu 2012. The review concluded that there was beneficial effect of using sealant compared to varnish; however, they emphasised that this was not statistically significant and the studies were of low quality.

A recent systematic review combined slightly different studies in their main meta‐analysis but reached the same conclusion as this review, that the evidence does not suggest either intervention is superior (Li 2020).

Figure 1

Study flow diagram.

Figure 2

'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

Figure 3

'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.

Analysis 1.1

Comparison 1: Resin fissure sealant versus fluoride varnish, Outcome 1: Dentinal caries at 2–3 years (yes/no)

Analysis 1.2

Comparison 1: Resin fissure sealant versus fluoride varnish, Outcome 2: Dentinal caries at 4 years (yes/no)

Analysis 1.3

Comparison 1: Resin fissure sealant versus fluoride varnish, Outcome 3: Dentinal caries at 9 years (yes/no)

Analysis 1.4

Comparison 1: Resin fissure sealant versus fluoride varnish, Outcome 4: Increment in decayed, missing and filled permanent teeth at 2 years

Analysis 1.5

Comparison 1: Resin fissure sealant versus fluoride varnish, Outcome 5: Increment in decayed, missing and filled permanent surfaces at 2 years

Analysis 2.1

Comparison 2: Resin‐modified glass ionomer fissure sealant versus fluoride varnish, Outcome 1: Dentinal caries at 12 months (yes/no)

Analysis 3.1

Comparison 3: Resin fissure sealant plus fluoride varnish versus fluoride varnish, Outcome 1: Dentinal caries at 24 months (yes/no)

Summary of findings 1. Resin‐based fissure sealant compared with fluoride varnish for preventing dental caries

Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	Number of participants (studies)	Certainty of the evidence (GRADE)	Comments
Resin‐based fissure sealant compared with fluoride varnish for preventing dental caries
Population: children and adolescents Setting: preventive dentistry Intervention: resin‐based fissure sealant applications on occlusal tooth surfaces of permanent first molars Comparison: fluoride varnish applications on occlusal tooth surfaces of permanent first molars
	Assumed risk	Corresponding risk
	Fluoride varnish	Resin‐based fissure sealant
Dentine caries in permanent molars (yes/no) Follow‐up: 2–3 years	228 per 1000	63 fewer per 1000 (from 32 more to 129 fewer)	OR 0.67 (95% CI 0.37 to 1.19)	1683 (4 studies)	⊕⊝⊝⊝ Very low^a,b,c	Data from 1 other study measuring DMFS and DMFT suggested a very small benefit for fissure sealants at 2‐year follow‐up. 4‐ and 9‐year data came from 1 study at high risk of bias and suggested a benefit for fissure sealants.
Adverse effects	None reported
The basis for the assumed risk* was the median risk in the fluoride varnish group. 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; DMFS: decayed, missing and filled permanent surfaces; DMFT: decayed, missing and filled permanent teeth; OR: odds ratio.
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.
^aDowngraded one level as studies at high risk of detection bias. ^bDowngraded one level due to severe heterogeneity (I² = 84%). ^cDowngraded one level for imprecision.

Summary of findings 1. Resin‐based fissure sealant compared with fluoride varnish for preventing dental caries

Summary of findings 2. Glass ionomer fissure sealant or resin‐modified glass ionomer fissure sealant compared with fluoride varnish for preventing dental caries

Outcomes	Results	Number of participants (studies)	Certainty of the evidence (GRADE)	Comments
Glass ionomer fissure sealant or resin‐modified glass ionomer fissure sealant compared with fluoride varnish for preventing dental caries
Population: children and adolescents Setting: preventive dentistry Intervention: glass ionomer or resin‐modified glass ionomer sealant applications on occlusal tooth surfaces of permanent first molars Comparison: fluoride varnish applications on occlusal tooth surfaces of permanent first molars
Dentine caries in permanent molars Follow‐up: 1, 2 and 3 years	No evidence of a difference between interventions in caries after 1, 2 and 3 years	995 (3 studies)	⊕⊝⊝⊝ Very low^a,b,c,d	Studies were clinically different so we did not combine them in meta‐analyses. 1 study included oral health education in both arms and found a benefit for sealant among children at high risk of caries.
Adverse effects	None reported
The basis for the assumed risk* (e.g. 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).
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.
^aOne study with high risk of bias comparing resin‐modified glass ionomer versus fluoride varnish after 1 year (Florio 2001). ^bThe other two studies at two years, with incomplete information and analyses, compared chemically cured glass ionomer versus fluoride varnish (Ji 2007). The third study actually evaluated whether additional benefit was derived by using resin‐modified glass ionomer sealants and fluoride varnishes among children receiving regular oral health education (Tagliaferro 2011). ^cOne study at three years comparing chemically cured glass ionomer versus fluoride varnish, assessed as having high risk of bias (extensive incomplete information and analyses) (Ji 2007). ^dDowngraded because a small number of trials had high risk of bias and used different designs and follow‐up times.

Summary of findings 2. Glass ionomer fissure sealant or resin‐modified glass ionomer fissure sealant compared with fluoride varnish for preventing dental caries

Summary of findings 3. Resin‐based fissure sealant plus fluoride varnish versus fluoride varnish alone for preventing dental caries

Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	Number of participants (studies)	Certainty of the evidence (GRADE)	Comments
Resin‐based fissure sealant plus fluoride varnish compared with fluoride varnish alone for preventing dental caries
Population: children and adolescents at school in Germany Setting: preventive dentistry Intervention: resin‐based fissure sealant + fluoride varnish applications on occlusal tooth surfaces of permanent first molars Comparison: fluoride varnish applications to occlusal tooth surfaces of permanent first molars
	Assumed risk	Corresponding risk
	Fluoride‐varnished teeth	Sealed + fluoride‐varnished teeth
Dentine caries in permanent molars Follow‐up: 2 years	223 per 1000	144 fewer per 1000 (from 87 fewer to 176 fewer)	OR 0.30 (95% CI 0.17 to 0.55)	92 (1 study)	⊕⊝⊝⊝ Very low^a,b,c	—
Adverse effects	Not measured
The basis for the assumed risk* (e.g. 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; OR: odds ratio.
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.
^aStudy conducted in the 1990s (Splieth 2001). ^bNo information on caries incidence among control teeth without treatment. Baseline caries of the study population (children five to eight years of age): mean decayed, missing and filled permanent surfaces 0.2. ^cDowngraded three levels because a single study (92 analysed participants) was conducted as early as the 1990s without information on caries incidence among control teeth without treatment, and although the study was otherwise well conducted, lack of blinding to outcome measurement caused further uncertainty about results.

Summary of findings 3. Resin‐based fissure sealant plus fluoride varnish versus fluoride varnish alone for preventing dental caries

Table 1. Caries data from studies with binary outcome

Resin FS vs FV: at 2–3 years
Split‐mouth studies	Both sound	FS sound FV carious	FS carious FV sound	Both carious	Proportion of decayed FV tooth surfaces to total FV surfaces	Becker‐Balagtas marginal OR (95% CI)
Raadal 1984 (sealant better)	131	31	15	31	0.30	0.67 (0.48 to 0.93) P = 0.02 ICC 0.44
Parallel‐group studies	Description of data					OR (95% CI)
Bravo 2005 (sealant better)	Calculated OR from data presented in Bravo 1996 (25/238 occlusal surfaces carious in sealant group; 71/252 surfaces carious in fluoride varnish group)					0.30 (0.18 to 0.49)
Liu 2012 (no difference)	OR based on model of multi‐level GEE logistic regression Additional information obtained from study author 124 children in sealant group, 116 in varnish group					0.87 (0.34 to 2.20)
Chestnutt 2017 (no difference)	The results presented as the proportion of children who developed dentine caries (D_4-6MFT) on ≥ 1 FPM at 36 months (19.6% in FS arm and 17.5% in FV arm). Sex and baseline caries prevalence were used to balance the randomisation. An adjusted model was also performed and taken as the primary analysis. 418 children in sealant group, 417 in varnish group					1.15 (0.81 to 1.63)
Pooled						OR 0.67 (0.37 to 1.19)
Resin FS vs FV: 4 years
Parallel‐group studies	Description of data					RR (95% CI)
Bravo 2005 (sealant better)	Results presented as RRs with cluster‐corrected standard error. A school class is a cluster, but several sealed and fluoride‐varnished teeth were present per child. Study authors calculated cluster‐corrected effect estimates when requested.					0.42 (0.21 to 0.84) P = 0.01
Resin FS vs FV: 9 years
Parallel‐group studies	Description of data
Bravo 2005 (sealant better)	Results presented as RRs with cluster‐corrected standard error. A school class is a cluster, but several sealed and fluoride‐varnished teeth were present per child. Study authors calculated cluster‐corrected effect estimates when requested. 26.6% of FS teeth and 55.8% of FV teeth had developed caries after 9 years (76.7% of control teeth without treatments)					0.48 (0.29 to 0.79) P = 0.004
Resin‐modified glass ionomer FS vs FV: 1 year
Parallel‐group studies	Description of data					OR (95% CI)
Florio 2001 (no difference)	Clustered data (several teeth per child). Data decided to analyse at a child level (i.e. data were dichotomised – did a child have caries or not) because decayed teeth were very few. Additional information obtained from study author indicated that the 2 decayed surfaces in the FV group were present in different children. 31 children in sealant group, 11 in varnish group Detailed data (Analysis 2.1)					0.18 (0.01 to 4.27) P = 0.29
Resin FS + FV vs FV: 2 years
Split‐mouth studies	Both sound	FS + FV sound FV carious	FS + FV carious FV sound	Both carious	Proportion of decayed control tooth surfaces to total control surfaces	Becker‐Balagtas marginal OR (95% CI)
Splieth 2001 (FS + FV better than FV alone)	129	32	7	7	0.22	0.30 (0.17 to 0.55) P < 0.0001
CI: confidence interval; FPM: first permanent molar; FS: fissure sealant; FV: fluoride varnish; GEE: generalised estimating equation; ICC: intracluster correlation coefficient; OR: odds ratio.

Table 1. Caries data from studies with binary outcome

Table 2. Criteria for 'Risk of bias' assessment

Random sequence generation (selection bias)	Was the method used to generate the allocation sequence appropriate to produce comparable groups?	We graded this domain to 'low' risk of bias if study authors described a random component in the sequence generation process (e.g. random number table, coin tossing, drawing of lots). If information about the random sequence generation process was not provided or was insufficient, we graded this domain to 'unclear' risk.
Allocation concealment (selection bias)	Was the method used to conceal the allocation sequence appropriate to prevent the allocation from being known in advance of, or during, enrolment?	We graded this domain to 'low' risk of bias if study authors described adequate concealment (e.g. by means of central randomisation, or sequentially numbered, opaque and sealed envelopes) and to 'high' risk of bias if inadequate concealment was documented (e.g. alternation, use of case record numbers, date of birth or day of the week) or if allocation concealment was not used. If insufficient or no information on allocation concealment was provided, the judgement was graded 'unclear' risk.
Blinding (performance bias)	Performance bias is looked at differently for the parallel‐group and split‐mouth studies.	Due to characteristics of each intervention, both participants and personnel are aware which of the 2 active preventive treatments has been applied. For parallel‐group studies, it was not possible to ensure that both groups followed a similar oral hygiene routine. The risk of bias was high. However, for the split‐mouth studies it is unlikely that the children undertook different oral hygiene practices in different areas of the mouth so performance bias was assumed to be of low risk.
Blinding of outcome assessment (detection bias)	Were outcome assessors blinded to the intervention a participant had received?	As sealant materials are visible, blinding of the outcome assessor is possible only if a sealant has been lost. Thus, outcome measurement is related to sealant retention and blinding of outcome assessor is usually impossible. However, it is difficult to assess how likely (or unlikely) it is that the outcome measurement is influenced by lack of blinding of outcome assessors in preventive sealant studies. Although the outcome assessors could not be blinded, the potential for bias could not be ignored. We decided to grade this domain as having 'low' risk of bias if study authors stated that the outcome assessor was not involved in the study design, and as having 'unclear' risk of bias if the study simply reported blinded outcome assessment or if blinding was indicated (e.g. examinations performed independently of previous records, outcome assessors not involved in applying treatments). If a trial reported nothing about blinding of outcome measurement, our judgement was 'high' risk of bias in this domain.
Incomplete outcome data (attrition bias)	How complete were the outcome data for primary caries outcomes? Were dropout rates and reasons for withdrawals reported? Were missing data imputed appropriately?	In caries prevention studies, follow‐up times can last several years. Studies with long follow‐up have the problem of high dropout rates causing uncertainty about data. We decided to base the judgement of this domain on caries efficacy outcome at 24 or 36 months (commonly used follow‐up times in sealant studies). When both follow‐up times were reported, we based our judgement on 24 months. If either of these 2 follow‐up times was not reported, we based our judgement on the first caries efficacy outcome reported in the study (which in this review should be ≥ 1 year). The risk of bias was assessed separately and was reported in the 'Risk of bias' table for caries outcomes for all reported follow‐up times. These assessments were taken into account in the overall risk of bias assessment for caries outcomes within a study. We decided to grade this domain as having 'low' risk of bias if the total proportion of missing outcome data was marginal (< 5%); or if the proportion of missing outcome data was < 25% regardless of the follow‐up time and groups (in parallel‐group studies) were balanced in numbers for missing data; or if missing data had been imputed using appropriate methods. If no information on reasons for dropout across intervention groups was provided, or if the proportion of missing data was documented as total proportion (5–25%), not by group in parallel‐group studies, our judgement was 'unclear' risk. Classifying missing data > 25% as having 'high' risk of bias in all study designs was a pragmatic approach to this domain to make the judgement uniform and transparent. If several teeth were sealed in a child's mouth (a child is a cluster), missing outcome data had to be stated (or counted) at child level (not at tooth level).
Selective reporting (reporting bias)	Were appropriate outcomes reported and were key outcomes missing?	To be included in this review, caries outcomes had to be reported. However, studies could report the outcome in different ways, e.g. incidence of dentinal carious lesion on treated occlusal surfaces of molars or premolars (yes or no); changes in mean figures of decayed, missing and filled surfaces (DMFS); or progression of caries lesion into enamel or dentine. In this review, selective outcome reporting was graded as 'low' risk of bias if the study's prespecified caries outcomes had been reported in the prespecified way.
Other sources of bias	This domain included information on comparability of intervention and control groups, and possible use of co‐interventions by group	Comparability of groups We decided to base our judgement of comparability of groups on baseline information given to groups available at follow‐up times because if only information provided at the start of the study is available, it is impossible to assess whether groups are balanced with each other after follow‐up time as well. The comparability of groups after follow‐up is especially problematic when small studies include children with several teeth and the dropout rate is high, even if dropouts are balanced in numbers and reasons between groups. If no information on the groups was available at follow‐up time, we decided that if the dropout rate (regardless of follow‐up time) was < 25% and dropouts were balanced in numbers and reasons by group, our judgement would be based on information given for groups at the start of the study. We decided to grade this domain as having 'low' risk of bias if groups were balanced in demographic characteristics (such as sex, age and social class) and in baseline caries risk level, or if possible imbalance of groups at baseline or after follow‐up (or both) had been taken adequately into account in the analyses. If baseline characteristics in parallel‐group studies were not given to groups available at follow‐up and the dropout rate was > 25%, we graded the study as having 'unclear' risk. Co‐interventions We decided to grade this domain as having 'low' risk of bias if groups were balanced in number and quality of co‐interventions, or if no co‐interventions were included in the protocol, and as having 'high' risk of bias if groups received different numbers or quality of co‐interventions during the trial. If no information was provided on co‐interventions, our judgement was 'unclear' risk.

Table 2. Criteria for 'Risk of bias' assessment

Table 3. Outcomes for each study

Study	New caries lesion (yes/no)	Changes in caries from baseline DMFS on occlusal surfaces	Changes in caries from baseline DMFS on all surfaces	Changes in caries from baseline DMFT on all teeth	Progression of enamel carious lesions into dentine on treated occlusal surfaces	Time taken to apply intervention	Number of visits to repair sealant or apply varnish	Adverse events
Bravo 2005	Yes at 2, 4, 9 years	—	—	—	—	—	Yes, over 4 years	Yes, over 4 years
Chestnutt 2017	Yes, at 3 years	—	—	—	—	—	—	Yes, over 3 years
Florio 2001	Yes, at 1 year	—	—	—	Yes, at 1 year	—	—	—
Ji 2007	Yes, at 3 years	—	—	—	—	—	—	—
Kalnina 2016	Yes, at 1 year but unable to use as 0 in both groups	—	—	—	—	—	—	Yes, over 1 year
Liu 2012	Yes, at 2 years	—	—	—	—	—	—	Yes, over 2 years
Raadal 1984	Yes, at 2 years	—	—	—	—	—	—	—
Salem 2014	Yes, at 2 years but unable to use data	—	—	—	—	—	—	—
Splieth 2001	Yes, at 2 years	—	Yes	—	—	Yes, over 2 years	—	Yes, over 2 years
Tagliaferro 2011	—	Yes, at 2 years	—	—	—	—	—	—
Tang 2014	—	—	Yes, at 2 years	Yes, at 2 years	—	—	—	—
DMFS: decayed, missing and filled permanent surfaces; DMFT: decayed, missing and filled permanent teeth.

Table 3. Outcomes for each study

Comparison 1. Resin fissure sealant versus fluoride varnish

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1.1 Dentinal caries at 2–3 years (yes/no) Show forest plot	4		Odds Ratio (IV, Random, 95% CI)	0.67 [0.37, 1.19]

1.1.1 Split‐mouth studies with paired data	1		Odds Ratio (IV, Random, 95% CI)	0.67 [0.48, 0.93]
1.1.2 Parallel‐group studies	3		Odds Ratio (IV, Random, 95% CI)	0.66 [0.26, 1.73]
1.2 Dentinal caries at 4 years (yes/no) Show forest plot	1		Risk Ratio (IV, Fixed, 95% CI)	0.42 [0.21, 0.84]

1.3 Dentinal caries at 9 years (yes/no) Show forest plot	1		Risk Ratio (IV, Fixed, 95% CI)	0.48 [0.29, 0.79]

1.4 Increment in decayed, missing and filled permanent teeth at 2 years Show forest plot	1	542	Mean Difference (IV, Fixed, 95% CI)	‐0.08 [‐0.14, ‐0.02]

1.5 Increment in decayed, missing and filled permanent surfaces at 2 years Show forest plot	1	542	Mean Difference (IV, Fixed, 95% CI)	‐0.09 [‐0.15, ‐0.03]

Comparison 1. Resin fissure sealant versus fluoride varnish

Comparison 2. Resin‐modified glass ionomer fissure sealant versus fluoride varnish

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
2.1 Dentinal caries at 12 months (yes/no) Show forest plot	1	21	Odds Ratio (M‐H, Fixed, 95% CI)	0.18 [0.01, 4.27]

Comparison 2. Resin‐modified glass ionomer fissure sealant versus fluoride varnish

Comparison 3. Resin fissure sealant plus fluoride varnish versus fluoride varnish

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
3.1 Dentinal caries at 24 months (yes/no) Show forest plot	1		Odds Ratio (IV, Fixed, 95% CI)	0.30 [0.17, 0.55]

Comparison 3. Resin fissure sealant plus fluoride varnish versus fluoride varnish