A National Study Exploring the Association Between Fluoride Levels and Dental Fluorosis

Key Points Question What is the association between systemic fluoride exposure and dental fluorosis? Findings This cross-sectional study of 2995 children and adolescents found that higher fluoride levels in water and plasma were associated with dental fluorosis. Meaning These findings suggest that public health policy related to water fluoride levels and fluoridation should consider balancing caries prevention with dental fluorosis risk.


Introduction
When given in an appropriate amount, fluoride helps prevent dental caries by hardening enamel and enhancing tooth remineralization.It does so by promoting the tooth's calcium and phosphate ion remineralization process in rebuilding a new surface on existing crystal remnants.These remineralized crystals incorporate fluoride and are more acid-resistant than the original enamel mineral, which further protects enamel from decay. 1 However, excess fluoride during tooth development can cause dental fluorosis, which are visible changes on an erupting tooth's enamel surface.Depending on the amount, duration, and timing of fluoride intake, fluorosis can appear in varying forms in both primary and permanent teeth.
Mild cases include scattered white flecks that are barely noticeable, while more moderate and severe cases can cause brown stains and rough, pitted surfaces. 2Dental fluorosis is only considered a risk to children 8 years or younger because permanent teeth are fully developed after this age. 3e oral health benefits of fluoride are validated by epidemiologic evidence.Several systematic reviews [4][5][6][7][8][9] support both the clinical effectiveness and cost-effectiveness of fluoridation.Drinking fluoridated water reduces tooth decay by approximately 25% in children and adults, 3,10 and every dollar spent on fluoridation yields as much as $32 in reduced dental care expenses. 11e only widely recognized harm from fluoridation is dental fluorosis.Most cases of dental fluorosis are mild, and, other than cosmetic changes, dental fluorosis does not cause symptoms or harm.In determining fluoride recommendations, policy makers sought to balance dental caries prevention while limiting the risk of dental fluorosis and other potential health harms. 12However, despite an abundance of studies related to fluoride, 13 fewer high-quality studies examine the association of water fluoride levels with the prevalence of dental fluorosis. 10,14is study used a nationally representative sample of children in the US to explore associations between fluoride exposures and dental fluorosis.The findings contribute to the literature by updating earlier research about dental fluorosis and can help policy makers and health care professionals to balance the risks and benefits of fluoride.

Study Design
This

Data Source
The study used data from NHANES from the 2013-2014 and 2015-2016 cycles (January 1, 2013, through December 31, 2016).These were different participants from the 2 cycles of data, which represented the cross-sectional design of the study.NHANES is a survey aimed at determining the health and nutritional status of all US residents, including adults and children.The survey consists of both interviews and physical assessments.Health interviews are performed at the respondent's home, and health assessments are performed in mobile examination centers (MECs) that travel across the country.Data collection for this continuous program began in 1999 with a nationally representative sample of approximately 5000 persons each cycle.More details regarding NHANES study procedures can be found elsewhere. 15

Inclusion Criteria
Parents of participants aged 6 to 15 years were asked whether the participants received fluoride supplements.This age range was included in the analyses because NHANES contained data of their fluoride measurements, dental fluorosis assessments, and covariates needed for this study.The dental fluorosis severity value was based on the second most affected tooth.The person's status would be determined by the less affected tooth if the 2 most affected teeth were not equally affected (NHANES 2016).In this study, the dental fluorosis variable was dummy coded, where DFI Յ 0.5 was assigned to participants with no fluorosis and DFI Ն 1.0 to those with fluorosis.

Independent Variables
This study used 2 continuous variables (plasma fluoride concentration and water fluoride concentration) and 1 binary variable (fluoride in supplement form) as independent variables.Selfreported responses to the following question were used to assess the fluoride supplement: Have you ever received prescription fluoride drops or fluoride tablets (yes or no)?Both plasma and water fluoride concentrations were analyzed and recorded at the MECs by laboratory personnel.To measure plasma fluoride concentration, each sample underwent measurement twice using the ion-specific electrode and hexamethyldisiloxane method, and then the mean of the 2 measurements was calculated.Fluoride concentration in water samples was also measured twice using an ion-specific electrode, 3 and then the mean was calculated.Based on the US Public Health Servicerecommended water fluoride concentration of 0.70 mg/L, 12 fluoride levels in the water were categorized as 0.30 mg/L or less (reference level), 0.31 to 0.50 mg/L (level 1), 0.51 to 0.70 mg/L (level 2), and greater than 0.70 mg/L (level 3) in this study.Plasma fluoride was also categorized into 4 levels, which were 0.30 μmol/L or less (reference level), 0.31 to 0.40 μmol/L (level 1), 0.41 to 0.50 μmol/L (level 2), and greater than 0.50 μmol/L (level 3).

Covariates
This study adjusted for covariates, which included sociodemographic factors: the child's age (6-11   years [hereinafter referred to as children] or 12-15 years [hereinafter referred to as adolescents]), the child's sex (male or female), the child's race or ethnicity (Mexican American, non-Hispanic Asian, non-Hispanic Black, non-Hispanic White, non-Mexican Hispanic, or other [all non-Hispanic individuals of >1 race]), family educational level (<9th grade, 9th-11th grades, high school graduate or attainment of a General Educational Development certificate, some college, or college graduate or above), the season of sample collection (November 1 through April 30 or May 1 through October 31), and the ratio of family income to the area poverty level.The family educational level refers to the educational level of the person who owns or rents the residence where the study participant resides. 17Statistical significance was defined as a 95% CI excluding 0 for differences and excluding 1 for ratios.
All analyses were performed using SPSS, version 28 (IBM Corporation).5).Fluoride supplements were associated with lower odds of dental fluorosis (AOR, 0.741 [95% CI, 0.739-0.742]),but those taking supplements were exposed to lower water fluoride levels (Table 5), indicating a potential interaction effect between fluoride supplements and water fluoride levels.Further regression analyses found that the association of dental fluorosis with fluoride supplements varied by water fluoride levels when data were combined from both cycles, with significant interaction evident at water fluoride levels of 0.31 to 0.50 mg/L (AOR, 1.12 [95% CI, 1.117-1.130])and greater than 0.70 mg/L (AOR, 1.08 [95% CI, 1.075-1.090])(eTable in Supplement 1).

Discussion
In this cross-sectional study of a nationally representative population of US children and adolescents aged 6 to 15 years, we found that compared with the reference groups of 0.30 mg/L or less for fluoride water concentration and a plasma level of 0.30 μmol/L or less, higher levels of fluoride in plasma and water were independently associated with an increased risk of dental fluorosis.These findings are consistent with previous studies that found dental fluorosis might occur even with low levels of fluoride exposure from water. 18,19To reduce the effects of water fluoridation, the DHHS and policy makers may need to reconsider current recommendations for water fluoridation.In addition, it was not surprising that children who used fluoride supplements experienced lower water fluoride concentration exposures than those who did not take any fluoride supplements.It was reassuring that in this group, fluoride supplements did not increase the risk of dental fluorosis.This finding supports the American Dental Association's recommendation that children at high risk for cavities with low fluoride levels in their drinking water can safely benefit from fluoride supplements. 20other key finding was that the overall prevalence of fluorosis for both the 2013-2014 cycle (87.3%)and 2015-2016 cycle (68.2%)was greater than the 23% prevalence reported in 2004 by the Centers for Disease Control and Prevention. 21While the prevalence may seem surprisingly high, it  parallels an upward trend identified by Wiener et al, 22 who reported an increase of 31.However, the full effect of the 2015 recommendation may not be evident until later NHANES cycles since some 2015 enrollees may have been exposed to higher fluoride concentrations when their permanent teeth were forming.Additional studies examining whether this decline persists will be important for assessing the new recommendation's impact on fluorosis.
The finding that well over half of the study group had some degree of fluorosis suggests that strategies to reduce the prevalence of dental fluorosis may be of value.However, when policies to reduce dental fluorosis are considered, the flip side is the potential loss of cavity protection.As policy makers weigh this balance, it should be noted that Do and Spencer 24 did not find a negative association between mild dental fluorosis and the perception of dental appearance, self-rated oral health, or child or parent perceptions about their oral health.Similarly, another study 25 reported no negative effects on oral health-related quality of life with mild fluorosis and even some suggestion of enhanced oral health-related quality of life with mild fluorosis.

Strengths and Limitations
A strength of this study is its generalizability to the childhood population in the US.However, several limitations need to be considered.First, this study was cross-sectional rather than longitudinal, and while it demonstrates an association between fluoride exposure and fluorosis, this does not necessarily mean causation.Having a longitudinal study would allow for observation of the effect of fluoride over a longer period.Additionally, measuring fluoride levels in drinking water and plasma at a single time point might not accurately reflect exposure levels in the years when the permanent teeth of the participants were forming.The data for individuals who are ingesting tap water and were not reported may also contribute to the exposure levels.Receiving a fluoride supplement was a selfreported variable from the parents, and the use of questionnaires are subject to recall bias and misreporting.Furthermore, fluoride supplement use did not include information such as the length of use and the fluoride dose.

Conclusions
In study used a cross-sectional design, analyzing data from the National Health and Nutrition Examination Survey (NHANES).Study reporting followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guideline for cross-sectional studies.The National Center for Health Statistics created public use files, and NHANES for the 2013-2014 and 2015-2016 cycles was approved by the National Center for Health Statistics Research Ethics Review Board, which waived the need for informed consent for the use of publicly available data.
from January 1 to April 30, 2023.Means and proportions were calculated for demographic variables and fluoride exposure using the unweighted data to reflect the survey sample characteristics and the weighted data to produce nationally representative estimates.Pearson correlation coefficients were computed between plasma fluoride concentration and water fluoride concentration.Independent samples t tests were used to explore differences in fluoride exposures across different groups.The associations between the oral health outcome (dental fluorosis) and fluoride exposures (water fluoride concentration, plasma fluoride concentration, and fluoride supplementation) were examined after controlling for age, sex, race and ethnicity, family educational level, ratio of family income to poverty, and period when the NHANES survey was administered using binary logistic regression.Regression models were run separately for the 2013-2014 data, the 2015-2016 data, and the combined data from 2013 to 2016.Separate analyses of the 2013-2014 data and the 2015-2016 data would allow for an examination of the 2015 recommendation by US Department of Health and Human Services (DHHS) to lower water fluoride concentrations. 12Additional regression models were run with incorporation of an interaction effect between the fluoride supplements and water fluoride levels controlling for covariates.The 95% CIs were reported.
6% in fluorosis prevalence in adolescents aged 16 and 17 years between 2001 to 2002 and 2011 to 2012.Our results also align with those of Neurath et al, 23 who found large increases in both the prevalence and severity of fluorosis over a 26-year period, peaking at a prevalence of 65% in 2011 to 2012.One reason for the increase in fluorosis prevalence may be the wider use of fluoride toothpaste and dental fluoride treatments.In contrast, 1 possible explanation for the decline in prevalence between the 2013-2014 and 2015-2016 cycles seen in this study may be the 2015 recommendation by the DHHS to lower water fluoride concentrations from 1.2 to 0.7 mg/L to minimize the risk of dental fluorosis. 12This policy change is also consistent with the lower plasma fluoride levels seen in the 2015-2016 group.
this cross-sectional study of 2995 participants using data obtained from the 2013-2014 and 2015-2016 NHANES cycles, exposure to higher concentrations of fluoride in water and having higher plasma fluoride levels were associated with a greater risk of dental fluorosis.In the 2013-2014 cycle, 87.3% of children exhibited some degree of dental fluorosis and 68.2% in the 2015-2016 cycle, a reduction that may be due to the 2015 DHHS recommendation to lower water fluoride concentrations.Further research is needed to assess the new fluoridation standard and to incorporate fluoride exposures from dietary fluoride supplements, topical fluoride application, fluoride toothpaste, fluoridated water, and natural products without fluoride to help policy makers balance caries prevention with dental fluorosis.

Table 1
presents the demographic characteristics.There were 1543 participants aged 6 to 15 years

Table 2 .
Comparison of Fluoride Exposure Across Groups in November to April (mean [SD], 0.41 [0.40] mg/L) (Table 2).Both the water fluoride level (mean [SD], 0.57 [0.39] mg/L) and plasma fluoride level (mean [SD], 0.47 [0.65] μmol/L) levels from May to October were higher than those from November to April in 2013-2014 (Table 2).Table 2 also reveals that the number of participants who used fluoride supplements increased from May through October (weighted 67.7%) compared with November through April (weighted 32.3%) in 2013-2014, while the number of participants receiving fluoride supplements from November to April (weighted 54.9%) was greater than the number of participants from May to In total, a weighted 87.3% of children and adolescents exhibited some degree of fluorosis (very mild, mild, moderate, and severe) in 2013-2014 and 68.2% in 2015-2016.Table 4 displays the associations between fluoride exposures and fluorosis, demonstrating that higher water fluoride concentrations were associated with an increased risk of dental fluorosis in children and adolescents for both the 2013-2014 and 2015-2016 cycles.After adjusting for covariates in the 2015-2016 cycle, both higher water and plasma fluoride concentrations were still independently associated with higher odds of dental fluorosis (adjusted odds ratio [AOR], 2.378 [95% CI, 2.372-2.383]for water fluoride; a Children are aged 6 to 11 years; adolescents, aged 12 to 15 years.JAMA Network Open | Public HealthAssociation Between Fluoride Levels and Dental Fluorosis JAMA Network Open.2023;6(6):e2318406.doi:10.1001/jamanetworkopen.2023.18406(Reprinted) June 23, 2023 5/10 Downloaded From: https://jamanetwork.com/ on 09/27/2023 higher than those AOR, 1.568 [95% CI, 1.564-1.571]for plasma fluoride) (Table

Table 3 .
Comparison Between Water Fluoride Concentration and Fluoride Supplementation

Table 4 .
Association Between Fluoride Exposure and Fluorosis a

Table 5 .
Association Between Fluoride Exposure and Fluorosis Adjusting for Covariates a Regression analyses were adjusted for age, sex, race and ethnicity, family educational level, ratio of family income to poverty, and 6-month period when surveyed.