Identifying Critical Periods of Neurotoxicity to Fluoride Exposure in Canadian Children

Abstract

Background: Fluoride is associated with IQ deficits during early brain development, but the period in which children are most vulnerable has not been established. We assessed sex-specific effects of fluoride on IQ across prenatal, infancy, and early childhood windows. Methods: Repeated exposures from 596 mother-child pairs in the Maternal-Infant Research on Environmental Chemicals cohort were analyzed using GEE to explore associations between fluoride exposures and IQ after adjustment for covariates and multiple comparisons. Fluoride was measured in urine spot samples collected during pregnancy trimesters and when children were between 1.9 and 4.4 years. Infant fluoride exposure was estimated from water fluoride concentration and duration of formula-feeding over the first year of life. The Wechsler Preschool and Primary Scale of Intelligence-III was administered at 3 to 4 years. Results: Among boys and girls, the association between fluoride and performance IQ (PIQ) significantly differed across exposure windows (p = .01). Among boys, prenatal exposure to fluoride was most strongly associated with adverse deficits on PIQ, B = -8.45 (95% CI: -12.90, -3.99), followed by infancy, B = -2.81 (95% CI: -6.59, 0.98), but not childhood, B = 0.20 (95% CI: -2.58, 2.99), respectively. Among girls, infancy exposure to fluoride was most strongly associated with adverse deficits on PIQ, B= -5.19 (95% CI: -8.84, -1.53), followed by prenatal and childhood exposures, B = -3.50 (95% CI: -9.51, 2.51), B = -2.05 (95% CI: -2.58, 2.99), respectively. Estimates for full-scale IQ were weaker but showed strongest effects for boys in the prenatal exposure period. Effects across all windows were nonsignificant among girls. We found no significant sex-specific associations between fluoride and verbal IQ. Conclusion: Adverse associations between fluoride exposures and cognitive outcomes may depend on timing and biological sex, with the prenatal window potentially critical for boys, while infancy is potentially critical for girls. Keywords: Fluoride, critical windows, water quality, children’s neuropsychology, epidemiology, toxicology.