Abstract: We included 28 trials (3 of which are new trials since the original review), involving 9140 children and adolescents. Most of these trials recruited participants from schools. Most of the studies (20) were at high risk of bias, with 8 at unclear risk of bias. Twenty-five trials (8479 participants) contributed data for meta-analysis on permanent tooth surfaces: the D(M)FS pooled prevented fraction (PF) estimate was 28% (95% confidence intervals (CI) 19% to 36%; P < 0.0001; with substantial heterogeneity (P < 0.0001; I2 = 82%); moderate quality evidence). Subgroup and metaregression analyses suggested no significant association between estimates of D(M)FS prevented fractions and the prespecified trial characteristics. However, the effect of fluoride gel varied according to the type of control group used, with D(M)FS PF on average being 17% (95% CI 3% to 31%; P = 0.018) higher in non-placebo-controlled trials (the reduction in caries was 38% (95% CI 24% to 52%; P < 0.0001, 2808 participants) for the 10 trials with no treatment as control group, and 21% (95% CI 15% to 28%; P < 0.0001, 5671 participants) for the 15 placebo-controlled trials. A funnel plot of the 25 trials in the D(M)FS PF meta-analysis indicated a relationship between prevented fraction and study precision, with an apparent lack of small studies with statistically significant large effects. The d(e/m)fs pooled prevented fraction estimate for the three trials (1254 participants) that contributed data for the meta-analysis on primary teeth surfaces was 20% (95% CI 1% to 38%; P = 0.04; with no heterogeneity (P = 0.54; I2 = 0%); low quality evidence). There was limited reporting of adverse events. Only two trials reported information on acute toxicity signs and symptoms during the application of the gel (risk difference 0.01, 95% CI -0.01 to 0.02; P = 0.36; with no heterogeneity (P = 36; I2 = 0%); 490 participants; very low quality evidence). None of the trials reported information on tooth staining, mucosal irritation or allergic reaction. The conclusions of this updated review remain the same as those when it was first published. There is moderate quality evidence of a large caries-inhibiting effect of fluoride gel in the permanent dentition. Information concerning the caries-preventive effect of fluoride gel on the primary dentition, which also shows a large effect, is based on low quality evidence from only three placebo-controlled trials. There is little information on adverse effects or on acceptability of treatment. Future trials should include assessment of potential adverse effects.

Plain-language summary: We included 28 studies in which over 9000 children (aged 2 to 15 years) were randomised to treatment with fluoride gel or to a control group using placebo gel or receiving no treatment. Study duration ranged from 1 to 4 years (with 13 studies lasting around 2 years). Study reports were published between 1967 and 2005. Thirteen studies took place in the USA, seven in Europe, four in Brazil and one each in Canada, Israel, China and Venezuela. This review update confirmed that fluoride gel can reduce tooth decay in children and adolescents. We combined the results of 25 trials and found that on average there is a 28% reduction in decayed, missing and filled tooth surfaces (21% reduction in trials that used a placebo gel in the control group and 38% reduction in trials where the control group received no treatment) in permanent teeth. From the three trials looking at the effect of fluoride gel on first or baby teeth, the evidence suggests that using fluoride gel results in a 20% reduction in decayed, missing and filled tooth surfaces. We found little information about unwanted or harmful effects or how well children and young people were able to cope with the application of the gel. The application of fluoride gel results in a large reduction in tooth decay in both permanent and baby teeth. We found little information about potential unwanted or harmful effects from accidental swallowing of the gel during treatment. As children often swallow gel during application, more research is needed on these effects. The evidence available for permanent teeth is of moderate quality. The evidence on baby teeth is low quality because of the small number of studies available. The evidence available for adverse effects is very low quality.