Abstract
BACKGROUND: Fluoride is globally recognised for its anticariogenic benefits and is delivered via community water fluoridation, fluoridated dentifrices, and dietary sources. However, emerging evidence raises questions about its potential impact on neurodevelopment. While animal and human studies suggest that high fluoride exposure, particularly during critical periods of brain maturation, may be associated with deficits in IQ and attention. Human studies remain heterogeneous in design, exposure assessment, and cognitive outcome measures. This thesis addresses key gaps by integrating multiple methodological approaches to clarify whether early-life fluoride exposure influences cognitive outcomes in children.METHODS: A multi-phase, multi‑methods approach guided this research. Phase I comprised a systematic review (registered in PROSPERO: CRD42021230649) of studies evaluating fluoride exposure, from gestation through 18 years of age and cognitive outcomes. Searches of seven electronic databases resulted in 46 eligible studies (six longitudinal; 40 cross‑sectional). Data were synthesised by exposure level (<2 mg/L vs. ≥2 mg/L), participant age, study design, and methodological quality (STROBE‑M). Phase II included two empirical investigations among Reception‑year children in Northeast England.
• Phase II A - An exploratory study comparing school‑readiness scores (Early Years Foundation Stage Profile) in naturally fluoridated (0.8–1.2 mg/L) versus non‑fluoridated (<0.3 mg/L) areas.
• Phase II B - An online parental survey measuring total daily fluoride intake (TDFI) from water, diet, and toothpaste and cognitive behaviours via the Conner’s Parent Rating Scale–Revised Short Form (CPRS‑R:S).
RESULTS: Systematic review: High‑exposure studies (≥2 mg/L) more frequently reported negative associations with cognitive outcomes, though only one of five “excellent” quality studies confirmed this link. Cross‑sectional designs predominated, underscoring the need for robust longitudinal research.
Exploratory study: Recruitment challenges limited statistical power. Key barriers included a lack of participants and demographic imbalances.
Online survey: Mean reported TDFI varied across participants and reported fluoride intake correlated with very mildly elevated CPRS‑R:S T‑scores in domains of inattention, hyperactivity and ADHD (r ≈ 0.33–0.43, p < 0.05). Subgroup analyses indicated no consistent gender differences.
DISCUSSION: Evidence from this multi‑methods research suggests a potential dose‑dependent relationship between elevated fluoride exposure and subtle decrements in cognitive and attention‑related outcomes. Methodological limitations, such as cross‑sectional designs, indirect exposures and small sample sizes, can change inferences. The exploratory study highlighted practical challenges in school‑based research, while the survey underscored the utility of parental reporting and biomarker triangulation.
CONCLUSION: This thesis advances understanding of fluoride’s non‑dental effects by synthesising existing literature and generating novel data on early childhood exposures. Findings support the hypothesis that high fluoride intake during critical developmental windows may influence cognitive function. Given public health reliance on fluoride for caries prevention, future large‑scale, longitudinal studies with precise exposure assessment and comprehensive confounder control are imperative. These will inform evidence‑based guidelines to optimise fluoride’s dental benefits while safeguarding the neurodevelopment of the vulnerable population.
| Date of Award | 29 Apr 2026 |
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| Original language | English |
| Awarding Institution |
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| Supervisor | Vida Zohoori (Supervisor), Ralph Marsland Duckworth (Supervisor) & Daniel Jones (Supervisor) |