Abstract

BackgroundPrevious animal and ecological studies have provided evidence for an earlier sexual maturation in females in relation to fluoride exposure; however, no epidemiological studies have examined the association between fluoride exposure and pubertal development in both boys and girls using individual-level biomarkers of fluoride. Capitalizing on an ongoing Mexican birth cohort study, we examined the association between concurrent urinary fluoride levels and physical markers of pubertal development in children.MethodsWe conducted a cross-sectional study of 157 boys and 176 girls at age 10–17 years living in Mexico City. We used ion-selective electrode-based diffusion methods to assess fluoride levels in urine, adjusting for urinary specific gravity. Pubertal stages were evaluated by a trained physician. Associations of fluoride with pubertal stages and age at menarche were studied using ordinal regression and Cox proportional-hazard regression, respectively.ResultsIn the entire sample, the geometric mean and interquartile range (IQR) of urinary fluoride (specific gravity adjusted) were 0.59 mg/L and 0.31 mg/L, respectively. In boys, our analysis showed that a one-IQR increase in urinary fluoride was associated with later pubic hair growth (OR = 0.71, 95% CI: 0.51–0.98, p = 0.03) and genital development (OR = 0.71, 95% CI: 0.53–0.95, p = 0.02). No significant associations were found in girls, although the direction was negative.ConclusionsChildhood fluoride exposure, at the levels observed in our study, was associated with later pubertal development among Mexican boys at age 10–17 years. Further research is needed to confirm these findings.

Highlights

  • Previous animal and ecological studies have provided evidence for an earlier sexual maturation in females in relation to fluoride exposure; no epidemiological studies have examined the association between fluoride exposure and pubertal development in both boys and girls using individual-level biomarkers of fluoride

  • With a one-interquartile range (IQR) increase (0.31 mg/L) in urinary fluoride, the odds of reaching a high stage of pubic hair growth decreased by 29% (Odds ratio (OR): 0.71, 95% confidence interval (CI): 0.51–0.98, p = 0.03); the odds of reaching a high stage of genitalia decreased by 29% (OR: 0.71, 95% CI: 0.53–0.95, p = 0.02) in boys

  • We found that specific gravity-adjusted urinary fluoride was negatively associated with pubertal stages for pubic hair growth and breast maturation adjusting for the same covariates, the associations did not reach significance (Table 6)

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Summary

Methods

Study population In this study, we included participants from the Early Life Exposures in Mexico to ENvironmental Toxicants (ELEMENT) project, which is an on-going birth cohort study of both pregnant women and their offspring in Mexico City. Chi-square test to examine the differences between categorical variables Covariates considered in this analysis as predictors of puberty or potential confounders included child age and BMI z-scores, maternal education [16] and marital status [17], as well as number of siblings at birth [18]. We determined the associations between specific gravity-adjusted urinary fluoride and pubertal stages for the maturation of breast, pubic hair and genitalia using multivariate ordinal regression models. We assessed the adjusted prospective association between childhood exposure to fluoride at age 6–12 years and pubertal development in boys and girls. Only a small subset of participants had data on childhood exposure fluoride, as measured by urinary fluoride at age 6–12 years with the adjustment of specific gravity in urine (n = 66 for boys and n = 72 for girls). Detailed information regarding the methods for fluoride analysis has been published elsewhere [11]

Results
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