Evidence that fluoride in the infant formula causes enamel fluorosis weak

Information was sourced from PubMed, the Cochrane Library, the Web of Science, Controlled Trials, Clinical Trials (a service of the US National Institutes of Health), ProQuest UMI (a dissertation and thesis database), National Institute for Health and Clinical Excellence, Virtual Health Library, Bireme-PAHO-WHO, and the Latin America and Caribbean Centre on Health Sciences Information, along with the reference lists of relevant reports and review articles. Authors were contacted for missing information.

Studies conducted in humans were selected if they evaluated fluorosis and infant formula. Studies focussed exclusively on primary teeth were excluded. There were no restrictions on study designs.

Two authors independently extracted data and assessed study quality. Disagreements were resolved by discussion. Summary odds ratios and confidence intervals were calculated using a random-effects model. Heterogeneity was quantified using the I(2) statistic and publications bias using a funnel plot and Egger test.

Twenty-seven out of 41 studies evaluating the effect of infant formula on enamel fluorosis risk were included. These 27 papers reported the results of 19 observational studies (comprising one prospective cohort study, five retrospective cohort studies, six case-control studies, four cross-sectional studies and three historical-control studies). Seventeen of these 19 studies reported odds ratios (OR) and, among these, infant formula consumption was associated with a higher prevalence of enamel fluorosis in the permanent dentition [summary OR, 1.8; 95% confidence interval (CI), 1.4-2.3]. The studies showed significant heterogeneity (66%) and evidence of publication bias (P 0.002). Metaregression suggests that the OR associating infant formula with enamel fluorosis increased by 5% for each 0.1-ppm increase in the reported levels of fluoride in the water supply (OR, 1.05; 95% CI, 1.02-1.09).

Infant formula consumption may be associated with an increased risk of developing at least some detectable level of enamel fluorosis, but this depends on the level of fluoride in the water supply. The evidence that the fluoride in the infant formula caused enamel fluorosis was weak, as other mechanisms could explain the observed association.