Infant Formula and Fluorosis; a Systematic Review

Infant formula (IF) has been evaluated as a potential cause for fluorosis in the US population. Professional organizations have provided variable advice on minimizing the impact of infant formula on fluorosis. Objectives: To provide a systematic review of controlled studies on the fluorosis risk associated with IF. Methods: Eight databases were systematically searched and information abstracted. Study quality was assessed and odds ratios, when obtainable, were combined using random-effects models. Results: Of the 968 potentially eligible titles, 40 studies met the inclusion criteria. Fourteen out of 40 studies reported including IF as a fluorosis risk factor in the materials and methods section, but results were not reported. A meta-analysis with the 26 remaining studies reporting on IF-fluorosis associations resulted in IF use in infancy being associated, on average, with a higher prevalence of fluorosis later in life (summary odds ratio=1.8; 95% confidence interval=1.4-2.3). There was significant heterogeneity among studies (I-squared=68%) and funnel plots were indicative of publication bias. The heterogeneity of fluorosis risk among studies may have been due to variability on fluoride content of the IF itself, variability in duration and frequency of IF use, differences in the assessment of fluorosis, and lack of estimates in some studies how the fluorosis risk associated with IF was influenced by different levels of water fluoridation. Conclusions: Publication bias may be distorting the evidence on IF and fluorosis. Among studies that reported a measure of association, infant formula use in infancy was associated with fluorosis. There is suggestive evidence this effect is due to fluoride content in IF or the fluoride levels in the water used to reconstitute IF, but confounding cannot be ruled out. Supported by ADA Foundation.