Prenatal exposure to fluoride and neuropsychological development in early childhood: 1-to 4 years old children

Environ Res. 2022 May 1:207:112181. doi: 10.1016/j.envres.2021.112181. Epub 2021 Oct 8.


Background: Cross-sectional and prospective studies have provided evidence of the neurotoxic effect of early exposure to fluoride (F) in pregnancy. It has been negatively associated with cognitive development during childhood, with most research conducted in areas with high F levels in community drinking water (CDW).

Method: Data from 316 to 248 mother-child pairs from the Infancia y Medio Ambiente (Childhood and Environment, INMA) birth cohort project with maternal urinary F level adjusted for creatinine (MUFcr) measurements in the first and third trimesters of pregnancy. Children's cognitive domains and intelligence indexes were evaluated using the Bayley Scales (age of 1) and the McCarthy Scales (age of 4). Multiple linear regression analyses were carried out adjusting for a wide range of covariates related to the child, mother, family context and other potential neurotoxicants.

Results: No association was found between MUFcr levels and Bayley Mental Development Index score. Nevertheless, regarding the McCarthy scales, it was found that per unit (mg/g) of MUFcr across the whole pregnancy, scores in boys were greater for the verbal, performance, numeric and memory domains (β = 13.86, CI 95%: 3.91, 23.82), (β = 5.86, CI 95%: 0.32, 11.39), (β = 6.22, CI 95%: 0.65, 11.79) and (β = 11.63, CI 95%: 2.62, 20.63) respectively and for General Cognitive Index (β = 15.4, CI 95%: 6.32, 24.48). For girls there was not any cognitive score significantly associated with MUFcr, being the sex-F interactions significant (P interaction <0.05). Including other toxicants levels, quality of family context or deprivation index did not substantially change the results.

Conclusions: In boys, positive associations were observed between MUFcr and scores in cognitive domains at the age of 4. These findings are inconsistent with those from some previous studies and indicate the need for other population-based studies to confirm or overturn these results at low levels of F in CDW.

Keywords: Children; Fluoride; Intelligence; Neuropsychological development; Pregnancy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child Development
  • Child, Preschool
  • Cross-Sectional Studies
  • Female
  • Fluorides* / toxicity
  • Fluorides* / urine
  • Humans
  • Infant
  • Male
  • Pregnancy
  • Prenatal Exposure Delayed Effects* / chemically induced
  • Prospective Studies


  • Fluorides