Question 1. How effective are the different fluoride interventions in preventing dental caries in children under 5 years of age?
The first studies reporting association between the natural fluoride content of drinking-water and decreased prevalence of caries date from 1930s. Currently, it is estimated that around 380 million people regularly consume artificially fluoridated water, in addition to 50 million who consume drinking water containing optimal fluoride concentrations naturally . Recent systematic reviews have summarized the effects of the existing literature and confirmed that fluoridated water reduces the prevalence of dental caries.
One Cochrane review (Iheozor-Ejiofor 2015) evaluated the effects of water fluoridation on the prevention of dental caries . The review authors included prospective controlled studies that assessed caries in a population receiving fluoridated water (naturally or artificially) and in a population receiving non-fluoridated water. The literature search was conducted up to February 2015. The review authors found very little contemporary evidence. Nine observational studies contributed to the meta-analysis on caries in deciduous teeth and were all conducted prior to 2000; six prior to 1980. The data come from Europe (five studies), Australia, Asia, North America and South America. Findings indicate that:
The use of fluoridated water compared to low or non-fluoridated water may reduce caries in dmft, with a mean difference (MD) in the reduction of caries of 1.81 (95% confidence interval [CI] 1.31 to 2.31; 9 studies, 44,268 participants; low certainty evidence). This translates to a 35% reduction in dmft compared to the median control group mean values.
The use of fluoridated water compared to low or non-fluoridated water may increase the percentage of caries free children by 15% in deciduous teeth (95%CI 11 to 19; 10 studies, 39,966 participants; low certainty evidence).
However, the confidence of the review authors in the size of the effect estimates ‘is limited by the observational nature of the study designs, the high risk of bias within the studies and, importantly, the applicability of the evidence to current lifestyles.’
In 2013, the US Community Preventive Services Task Force recommended fluoridation of community water sources ‘based on strong evidence of effectiveness in reducing dental caries’ . These findings were based on an existing systematic review (McDonough 2000) combined with an updated search for recent evidence . Most of the included studies were from the US or other high-income countries. Authors reported ‘a decrease in new dental caries after community water fluoridation began and an increase in new dental caries when it was stopped’. Their main findings showed that water fluoride initiation led to a median decrease of 15.2 percentage points in caries (12 studies), and to a decrease in caries on dmft with a median difference of − 2.25 (interquartile range − 3.63 to − 1.28; 10 studies).
This same document also reported the findings of a systematic review looking at economic evidence, stating that ‘the economic benefit of community water fluoridation is greater than the cost’  (see original document for more details).
‘Since 1986, the WHO International Programme for Milk Fluoridation has promoted and supported programmes aimed at demonstrating the feasibility for community use of fluoridated milk for caries prevention’ . O’Mullane et al. noted the existence of three systematic reviews looking at the effects of milk fluoridation for preventing dental caries, and reported that all included studies showed a ‘reduction in dental decay among those consuming/receiving fluoridated milk’ . We report below the main findings of the most recent systematic review on this topic.
One Cochrane review (Yeung 2015) assessed the effects of fluoridated milk on the prevention of dental caries at a community level . Only randomized controlled trials (RCTs) comparing fluoridated versus non-fluoridated milk with an intervention and follow-up period of at least 2 years were included. The literature search was conducted up to November 2014. Only one trial was identified, conducted in Russia in 2004, unpublished. Authors judged the overall quality of the evidence as low, and found that:
After 3 years, fluoridated milk in children compared to non-fluoridated milk may reduce caries in dmft (MD -1.14; 95%CI − 1.86 to − 0.42; one trial, 166 participants; low certainty evidence), equivalent to a prevented fraction of 31%.
After 3 years, fluoridated milk compared to non-fluoridated milk in children may reduce caries in decayed-missing-filled teeth from the permanent dentition (MD -0.13; 95%CI − 0.24 to − 0.02; one trial, 166 participants; low certainty evidence). The disease level was very low, resulting in a small absolute effect size (not quantified).
O’Mullane et al. reported that studies looking at effect of salt fluoridation for preventing dental caries found similar findings than those obtained with water fluoridation, and that ‘when most salt for human consumption is fluoridated, the community effectiveness of salt fluoridation approximates that of water fluoridation’ . Studies also showed ‘acceptability by the public, no increase in individual salt consumption, no proven related increase in enamel fluorosis, no other negative health impacts reported, and very low per capita costs’.
Individual fluoride supplementation
One Cochrane review (Tubert-Jeannin 2011) looked at the efficacy of fluoride supplements for preventing dental caries in children . Eligible criteria were RCTs or quasi-RCTs comparing fluoride supplements including tablets, drops and lozenges, with no systemic fluoride supplement or with topical fluorides or other preventive measures, with at least 2 years of follow-up. The literature search was conducted up to May 2011. Data for deciduous teeth were provided by four studies out of the 11 included studies in the review. These four studies were conducted in Sweden, Taiwan, the UK and the US, and published between 1985 and 2000. The risk of bias was judged as unclear for most of the domains for all included studies. The main findings were:
Fluoride supplements versus no fluoride supplements: the review authors concluded that ‘the effect of fluoride supplements was unclear on deciduous or primary teeth.’ Indeed, there was a beneficial effect of fluoride supplements in children with a 73% reduction (95%CI 46 to 99) of caries in dmfs. But this was from a single small study (n = 175) with children with cleft lip and/or palate; certainty of the evidence was rated as very low. The effect was estimated with a 46% reduction (95%CI 8 to 83) of caries in dmft. Two studies (696 participants) were included, with high heterogeneity (no significant effect in one study, strong beneficial effect in the other study). The certainty of the evidence was rated as very low.
Fluoride supplements versus topical fluorides or other preventive measures: there was no differential effect on deciduous tooth surfaces (13% reduction in d(m)fs; 95%CI − 7 to 33; 2 trials, 1051 participants; moderate certainty evidence).
The systematic review commissioned by the USPSTF to update their recommendations found no new trials since their previous 2004 systematic review that assessed the effectiveness of oral fluoride supplementation in children [2, 13]. Six studies were included in the 2004 systematic review. Among them, only one was a randomized trial, which is also included in the Cochrane review we described above . For fluoride supplementation compared to placebo or no supplementation, authors found relative reductions from 32 to 72% for dmft, and from 38 to 81% for dmfs. The review authors concluded that ‘although the studies had some methodological limitations, such as lack of adjustment for potential confounders, inadequate blinding, or unreported attrition, and were fairly heterogeneous, they support the conclusion that oral fluoride supplementation leads to decreased dental caries in children 5 years and younger who have inadequate fluoridation in their water’ .
According to O’Mullane et al., ‘a number of systematic and other reviews have concluded that the quality of the reviewed studies was generally low and the evidence of a caries preventive effect on the primary and permanent dentitions was inconsistent’ . After the assessment of several factors such as compliance and associated enamel fluorosis, they concluded that oral fluoride supplements have limited application as a public health measure.
Timing and dosage of oral fluoride supplementation
The systematic review commissioned by the USPSTF aimed to look at the evidence for timing and dosage of preventive fluoride interventions . They found no studies that specifically addressed the dosage and timing of oral fluoride supplementation in children with inadequate water fluoridation. Recommendations on the dosage and on the age when to start oral fluoride supplementation are based on several factors including the level of fluoride in the water consumed by the population, and may therefore differ according to settings [2, 16].
Topical fluorides are defined as ‘delivery systems which provide fluoride to exposed surfaces of the permanent and primary dentition, at elevated concentrations for a local protective effect and are therefore not intended for ingestion’ . They can be professionally applied (gels, varnishes, foam, slow-release devices and solutions) or self-applied (toothpastes and mouth rinses).
Fluoride toothpaste is ‘the most widely used method for maintaining a constant low level of fluoride in the oral environment’ and ‘its widespread use is considered to have played an important role in the decline in dental caries in industrialised countries in recent decades’ . Several systematic reviews demonstrated the effectiveness of fluoride toothpastes in preventing dental caries . We report below the findings of the two recent reviews, one published by the Cochrane Library in 2019, and one commissioned by the WHO and published in 2014 [9, 22].
One Cochrane review (Walsh 2019) looked at the effects of toothpastes of different fluoride concentrations in preventing dental caries . The review authors included RCTs that compared tooth brushing with fluoride toothpaste and tooth brushing with a non-fluoride toothpaste or toothpaste of a different fluoride concentration among children between one and 6 years of age, with a minimum of one-year follow-up. The literature search was conducted up to August 2018. Eight studies were included, that were conducted in Brazil (3 studies), the UK (2 studies), China, France and Germany and published between 1982 and 2014. The main findings were:
The use of 1500 ppm fluoride toothpaste compared to a non-fluoride toothpaste probably reduces caries in dmfs (MD of − 1.86; 95% CI − 2.51 to − 1.21; one trial, 998 participants; moderate certainty evidence).
The use of 1450 ppm compared to 440 ppm fluoride toothpaste probably slightly reduces caries in dmft (MD -0.34; 95%CI − 0.59 to − 0.09; 1 trial, 2362 participants; moderate certainty evidence).
The use of 1055 to 1100 ppm compared to 500 to 550 ppm fluoride toothpaste probably has similar effects in reducing caries in dmfs (MD -0.05; 95%CI − 0.38 to 0.28; two trials, 1958 participants; moderate certainty evidence), and in reducing caries in dmft (MD -0.27; 95%CI − 0.60 to 0.60; one trial, 905 participants; low certainty evidence)
The use of 1450 ppm compared to 250 ppm fluoride toothpaste may slightly reduce caries in dmfs (MD -1.20; 95%CI − 2.92 to 0.52; 1 study, 172 participants; low certainty evidence) and in dmft (MD -0.40; 95%CI − 1.14 to 0.34; 1 study, 172 participants; low certainty evidence).
Another systematic review (Wright 2014) assessed the efficacy of fluoride toothpaste use in caries prevention among children younger than 6 years . The literature search was conducted up to April 2015. Authors included all study designs other than case reports and narrative reviews. Fourteen trials that met their inclusion criteria (outcome caries) were selected, including six of the eight RCTs included in the Walsh Cochrane review. The authors judged all 14 trials with an overall high risk of bias. Their main findings were:
Fluoride toothpaste versus control or placebo, in participants classified as ‘high-risk populations’:
○ The use of 1000 to 1500 ppm toothpaste probably slightly reduces caries in dmfs (MD -0.24; 95%CI − 0.36 to − 0.13; six trials [one included in Walsh 2019]; certainty of the evidence not graded) and in dmft (MD -0.24; 95%CI − 0.41 to − 0.06; three trials [none included in Wash 2019]; certainty of the evidence not graded).
○ The use of toothpaste with < 1000 ppm may slightly reduce or have similar effect on caries in dmfs (MD -0.24; 96%CI: − 0.66 to 0.18; two trials [none included in Walsh 2019]; certainty of the evidence not graded) and in dmft (MD -0.16; 95%CI − 0.46 to 0.15; two trials [none included in Walsh 2019]; certainty of the evidence not graded).
High versus low fluoride concentration:
○ The use of high (1055–1450 ppm) versus low (250–550 ppm) fluoride concentration probably has similar effects in reducing caries in dmfs (MD -0.04; 95%CI − 0.12 to 0.03; three trials [all three included in Walsh 2019]; certainty of the evidence not graded), but may slightly reduce caries in dmft (MD -0.10; 95%CI − 0.14 to − 0.05; four trials [three of them included in Walsh 2019]; certainty of the evidence not graded).
Overall, while the evidence supports the benefits of fluoride toothpastes for preventing caries in children, the evidence for the effects of the different levels of fluoride concentration is more limited. Risk of dental fluorosis for different fluoride concentrations (see below under ‘Safety of fluoride interventions’) should be considered when choosing an optimal fluoride toothpaste concentration.
Other topical fluoride interventions: gels and varnishes
Although mouth rinses are another topical fluoride intervention used in the prevention of dental caries, we do not review its effectiveness in this document, as we focus in children under the age of 5 years.
One Cochrane review (Marinho 2015) looked at the effectiveness of topically applied fluoride gels for preventing dental caries in children and adolescents . The review authors included RCTs and quasi-RCTs in which the intervention was applied for at least 1 year. The literature search was conducted up to November 2014. Among the 28 included trials, three of them looked at the effectiveness of fluoride gels among children under 6 years of age for preventing dental caries in primary teeth. These three trials were conducted in Germany, the Netherlands and the US, and were published between 1978 and 2004. The two oldest trials were judged at high risk of attrition bias. Findings showed that fluoride gel versus placebo or no treatment result in a 20% reduction in dmfs (95%CI 1 to 38; three trials, 1254 participants; low certainty evidence). There were no data in dmft. We do not report findings on permanent surfaces and teeth as this is beyond the scope of this summary.
Another Cochrane review from the same first author (Marinho 2013), assessed the effectiveness of topically applied fluoride varnishes for preventing dental caries in children and adolescents . Authors included RCTs and quasi-RCTs that assessed topical fluoride varnishes, using any fluoride agent at any concentration, with any technique of application and with a frequency of application of at least once a year. The literature search was up to May 2013. Twenty-two trials were included; eight were in children between one and 5 years of age for assessing caries prevention in primary teeth. However, ten trials reported data on primary teeth and were included in the meta-analysis. These ten trials were conducted in Canada (two trials), China (two trials), Sweden (two trials), Brazil, India, the UK and the US, and were published prior to 2000 (three trials) and between 2000 and 2011 (seven trials). Findings showed that fluoride varnish compared to placebo or no treatment result in a 37% reduction in d(e/m) fs (95%CI 24 to 51; 10 trials, 3804 participants; moderate certainty evidence), and in a 65% reduction in d(e/m) ft. (95%CI 48 to 82; two trials, 323; certainty of the evidence not graded). We do not report findings on permanent surfaces and teeth as this is beyond the scope of this summary.
The systematic review commissioned by the USPSTF to update their recommendations found three new trials since their previous 2004 systematic review that assessed professionally applied topical fluoride varnish in children aged 5 years and younger . Two of them are included in the Cochrane review described above . The third one was conducted in an Australian aboriginal community with water fluoridation levels of 0.6 ppm for more than 90% of participants, using a cluster design. It was published in 2011. They found similar findings with an association between use of fluoride varnish and decreased incidence of caries after 2 years. For the three recent studies identified, the absolute mean reductions in the number of affected tooth surfaces ranged from 1.0 to 2.4 [2, 13].
Overall, professionally-applied topical fluorides such as gels and varnishes are effective in preventing dental caries, and are generally indicated for persons at high risk of dental caries and for patients with special needs, especially in communities with low exposure to fluoride [4, 16].
Timing and dosage of topical fluoride interventions
No studies addressed the age at which to start and stop the use of fluoride varnish . The USPSTF review authors noted that ‘available trials of fluoride varnish enrolled children ages 3 to 5 years; however, given the mechanism of action of this intervention, benefits are very likely to accrue starting at the time of primary tooth eruption.’
Regarding the effect of frequency of fluoride varnish application, ‘limited evidence found no clear effect on caries increment between performing a single fluoride varnish once every 6 months versus once a year or between a single application every 6 months versus multiple applications once a year or every 6 months’ . The review authors concluded that ‘the optimum frequency of fluoride varnish application is not known.’