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Estimating the causal effect of fluoride intake on caries trajectories from childhood to early adulthood with marginal structural models
Journal article   Peer reviewed

Estimating the causal effect of fluoride intake on caries trajectories from childhood to early adulthood with marginal structural models

Chukwuebuka Ogwo, Philips Okeagu, Grant Brown, Daniel Caplan, John Warren and Steven Levy
Journal of dentistry, Vol.164, 106259
01/01/2026
DOI: 10.1016/j.jdent.2025.106259
PMCID: PMC12790479
PMID: 41276066
url
https://pmc.ncbi.nlm.nih.gov/articles/PMC12790479/View
Open Access

Abstract

To identify the longitudinal changes in caries trajectory groups membership from childhood to young adulthood using unsupervised machine learning and estimate the effect of fluoride intake on trajectory group membership using causal inference methods. This longitudinal analysis used data from 560 participants in the Iowa Fluoride Study who completed at least two dental examinations at ages 9, 13, 17, and 23. The primary outcome was caries experience measured by D2+MFS counts, and the main exposure variable was total daily fluoride intake from all sources. Our analysis was performed in two stages: 1) Trajectory analysis using the K-means for Longitudinal Data algorithm to identify caries trajectory group membership, 2) Causal inference estimation using marginal structural models with inverse probability weighting using covariate-balancing propensity scores to estimate the effect of fluoride on trajectory membership. Two trajectory groups were identified: Low (80.2 %) and High (19.8 %) caries trajectory groups. Mean D2+MFS scores rose steadily with age, with the most pronounced increase between ages 13 and 17 in the high trajectory group. Fluoride intake at age 13 demonstrated a significant protective effect (OR=0.15; 95 % CI: 0.04–0.60), with reduced odds of High caries trajectory group membership. The effect of cumulative average fluoride intake was protective but not statistically significant (OR=0.39; 95 % CI: 0.10–1.57). Sensitivity analyses using alternative weight truncation supported the robustness of these estimates. Fluoride intake during early adolescence appears to be a critical protective factor against high caries trajectory development, highlighting the importance of maintaining adequate fluoride exposure during key developmental periods. Adequate fluoride intake during adolescence significantly reduces long-term caries risk by altering disease trajectory patterns. This study identifies early adolescence as a critical window for preventive intervention, supporting targeted fluoride exposure strategies and emphasizing the life-course importance of fluoride in promoting durable enamel health and preventing cumulative oral disease.
 Dental Caries Fluorides Causal Inference Cohort studies Disease trajectory Inverse probability weighting Longitudinal Studies Marginal Structural Models

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