Abstract: 25 studies were included: 2 RCTs, 1 cohort study, 6 case-control studies and 16 cross-sectional surveys. Only one RCT was judged to be at low risk of bias. The other RCT and all observational studies were judged to be at moderate to high risk of bias. Studies were included in four intervention/exposure comparisons. A statistically significant reduction in fluorosis was found if brushing of a child's teeth with fluoride toothpaste commenced after the age of 12 months odds ratio 0.70 (random-effects: 95% confidence interval 0.57 to 0.88) (data from observational studies). Inconsistent statistically significant associations were found between starting using fluoride toothpaste/toothbrushing before or after the age of 24 months and fluorosis (data from observational studies). From the RCTs, use of higher level of fluoride was associated with an increased risk of fluorosis. No significant association between the frequency of toothbrushing or the amount of fluoride toothpaste used and fluorosis was found. There should be a balanced consideration between the benefits of topical fluorides in caries prevention and the risk of the development of fluorosis. Most of the available evidence focuses on mild fluorosis. There is weak unreliable evidence that starting the use of fluoride toothpaste in children under 12 months of age may be associated with an increased risk of fluorosis. The evidence for its use between the age of 12 and 24 months is equivocal. If the risk of fluorosis is of concern, the fluoride level of toothpaste for young children (under 6 years of age) is recommended to be lower than 1000 parts per million (ppm). More evidence with low risk of bias is needed. Future trials assessing the effectiveness of different types of topical fluorides (including toothpastes, gels, varnishes and mouthrinses) or different concentrations or both should ensure that they include an adequate follow-up period in order to collect data on potential fluorosis. As it is unethical to propose RCTs to assess fluorosis itself, it is acknowledged that further observational studies will be undertaken in this area. However, attention needs to be given to the choice of study design, bearing in mind that prospective, controlled studies will be less susceptible to bias than retrospective and/or uncontrolled studies.

Plain-language summary: The aim of this review was to evaluate whether the use of fluoride toothpaste by children is associated with an increased risk of developing dental fluorosis in children. The review included 25 studies of different designs; some providing stronger evidence than others. There is some evidence that brushing a child's teeth with a toothpaste containing fluoride, before the age of 12 months, may be associated with an increased risk of developing fluorosis. There is stronger evidence that higher levels of fluoride (1000 parts per million (ppm) or more) in toothpaste are associated with an increased risk of fluorosis when given to children under 5 to 6 years of age. However, for some children (those considered to be at high risk of tooth decay by their dentist), the benefit to health of preventing decay may outweigh the risk of fluorosis. In such circumstances, careful brushing by parents/adults with toothpastes containing higher levels of fluoride would be beneficial.