Importance: Recent studies in Canadian and Mexican populations suggest an association of higher prenatal fluoride exposure with poorer neurobehavioral development, but whether this association holds for US-based populations is unknown.Objective: To examine associations of third trimester maternal urinary fluoride (MUF) with child neurobehavior at age 3 years in the US.Design, Setting, and Participants: This prospective cohort study utilized urine samples archived from 2017 to 2020 and neurobehavioral data assessed from 2020 to 2023 from the Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) pregnancy cohort, which consisted of predominately Hispanic women residing in Los Angeles, California. Cohort eligibility criteria at recruitment included being 18 years of age or older, less than 30 weeks’ gestation, and a fluent English or Spanish speaker. Exclusion criteria included having a disability preventing participation or provision of informed consent, being HIV positive or incarcerated, and having a multiple gestation pregnancy. There were 263 mother-child pairs who completed the 3-year study visit. In this analysis, women who reported prenatal smoking were excluded. Data analysis was conducted from October 2022 to March 2024.Exposure: Specific gravity-adjusted MUF (MUF_SG), a biomarker of prenatal fluoride exposure.Main Outcomes and Measures: Neurobehavior was quantified using the Preschool Child Behavior Checklist (CBCL), which included composite scores for Total Problems, Internalizing Problems, and Externalizing Problems. CBCL composite T scores range from 28 to 100. T scores from 60 to 63 are in the borderline clinical range, whereas scores above 63 are in the clinical range. Linear and logistic regression models adjusted for covariates were conducted.Results: A total of 229 mother-child pairs (mean [SD] maternal age, 29.45 [5.67] years; 116 female children [50.7%] and 113 male children [49.3%]) who had MUF_SG measured were included in the study. Median (IQR) MUF_SG was 0.76 (0.51-1.19) mg/L, and 32 participants (14.0%) had a Total Problems T score in the borderline clinical or clinical range. A 1-IQR (0.68 mg/L) increase in MUF_SG was associated with nearly double the odds of the Total Problems T score being in the borderline clinical or clinical range (odds ratio, 1.83; 95% CI, 1.17-2.86; P = .008), as well as with a 2.29-point increase in T score for the Internalizing Problems composite (B = 2.29; 95% CI, 0.47-4.11; P = .01) and a 2.14-point increase in T score for the Total Problems composite (B = 2.14; 95% CI, 0.29-3.98; P = .02).Conclusions and Relevance: In this prospective cohort study of mother-child pairs in Los Angeles, California, prenatal fluoride exposure was associated with increased neurobehavioral problems. These findings suggest that there may be a need to establish recommendations for limiting fluoride exposure during the prenatal period.

Current conceptualizations of dental caries etiology center primarily on the local role of sugar, starch, or other fermentable carbohydrates on tooth enamel demineralization—a well-established and empirically supported mechanism. However, in addition to this mechanism, studies dating back to the early 1900s point to an important systemic role of diet and nutrition, particularly from pasture-raised animal-source foods (ASF), in dental caries etiology and arrest. Findings from animal and human studies suggest that adherence to a diet high in calcium, phosphorus, fat-soluble vitamins A and D, and antioxidant vitamin C, as well as low in phytates, may contribute to arrest and reversal of dental caries, particularly among children. Furthermore, findings from observational and experimental studies of humans across the life-course suggest that fat-soluble vitamins A, D, and K2 may interact to protect against dental caries progression, even within a diet that regularly contains sugar. While these historic studies have not been revisited in decades, we emphasize the need for them to be reinvestigated and contextualized in the 21st century. Specifically, methodologically rigorous studies are needed to reinvestigate whether historical knowledge of systemic impacts of nutrition on dental health can help to inform current conceptualizations of dental caries etiology, prevention, and arrest.

Background/Objectives: Urinary fluoride (UF) is the most well-established biomarker for fluoride exposure, and understanding its distribution can inform risk assessment for potential adverse systemic health effects. To our knowledge, this study is the first to report distributions of UF among youth according to sociodemographic factors in a nationally representative United States (US) sample. Methods: The study included 1191 children aged 6-11 years and 1217 adolescents aged 12-19 years from the National Health and Nutrition Examination Survey (NHANES) 2015–2016. We examined UF according to sociodemographic variables as well as Spearman correlations between UF and plasma fluoride. Survey-weighted quantile regression examined associations between tap water fluoride and UF levels adjusted for covariates. Results: The average age of participants was 12.5 years. The median (IQR) UF and water fluoride concentrations were 0.52 (0.50) mg/L and 0.39 (0.54) mg/L, respectively. Children had higher UF levels than adolescents and males had higher UF levels than females. UF differed according to race/ethnicity among both children and adolescents. Specifically, non-Hispanic Black youth tended to have higher UF levels than all participants except for those classified as other race/multiracial. UF and plasma fluoride were moderately correlated for children and adolescents. Higher water fluoride levels were associated with higher UF levels, and the magnitudes of association were larger at higher quantiles of UF (β = 0.14, p < 0.001; β = 0.20, p< 0.001 at the 25th and 50th quantiles, respectively). The magnitude of association between water fluoride and UF was the largest for non-Hispanic Black participants (predictive margin = 0.3, p < 0.001). Conclusions: Non-Hispanic Black youth in the US may have greater fluoride exposure and receive more of their fluoride intake from tap water than youth of other races/ethnicities. Factors contributing to potential racial/ethnic disparities in fluoride exposure within the US warrant further investigation so that they can be mitigated to reduce the potential for harm.

Background: Fluoride is ubiquitous in the United States (US); however, data on biomarkers and patterns of fluoride exposure among US pregnant women are scarce. We examined specific gravity adjusted maternal urinary fluoride (MUFsg) in relation to sociodemographic variables and metal co-exposures among pregnant women in Los Angeles, California. Methods: Participants were from the Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) cohort. There were 293 and 490 women with MUFsg measured during first and third trimesters, respectively. An intra-class correlation coefficient examined consistency of MUFsg between trimesters. Kruskal–Wallis and Mann-Whitney U tests examined associations of MUFsg with sociodemographic variables. Covariate adjusted linear regression examined associations of MUFsg with blood metals and specific gravity adjusted urine metals among a subsample of participants within and between trimesters. A False Discovery Rate (FDR) correction accounted for multiple comparisons. Results: Median (IQR) MUFsg was 0.65 (0.5) mg/L and 0.8 (0.59) mg/L, during trimesters one and three respectively. During both trimesters, MUFsg was higher among older participants, those with higher income, and White, non-Hispanic participants than Hispanic participants. MUFsg was also higher for White, non-Hispanic participants than for Black, non-Hispanic participants in trimester three, and for those with graduate training in trimester one. MUFsg was negatively associated with blood mercury in trimester one and positively associated with blood lead in trimester three. MUFsg was positively associated with various urinary metals, including antimony, barium, cadmium, cobalt, copper, lead, nickel, tin, and zinc in trimesters one and/or three. Conclusions: MUFsg levels observed were comparable to those found in pregnant women in Mexico and Canada that have been associated with poorer neurodevelopmental outcomes. Lower urinary fluoride levels among Hispanic and non-Hispanic Black participants in MADRES compared to non-Hispanic White participants may reflect lower tap water consumption or lower fluoride exposure from other sources. Additional research is needed to examine whether MUFsg levels observed among pregnant women in the US are associated with neurodevelopmental outcomes.

Higher fluoride in plasma has been associated with lower eGFR among adolescents in the National Health and Nutrition Examination Survey (NHANES); however, whether fluoride exposure may contribute to decreased kidney function or fluoride may accumulate in plasma from lower kidney filtration could not be parsed. We examined the presence of dental fluorosis (DF; reflecting chronic fluoride exposure during tooth development) among adolescents and young adults and urinary fluoride (UF) levels among adolescents in relation to kidney and liver parameters in the United States (US). Participants were 1,031 adolescents (aged 12–19 years) and 734 young adults (aged 20–29 years) from NHANES 2015–2016. DF was derived from Dean’s Fluorosis Index (DFI), and defined as any DFI score indicating very mild, mild, moderate, or severe fluorosis, while scores of normal and questionable were categorized as no fluorosis. Kidney or liver function parameters included estimated glomerular filtration rate (eGFR), serum uric acid, the urinary albumin to creatinine ratio, blood urea nitrogen (BUN), gamma glutamate transferase, aspartate aminotransferase, alkaline phosphatase, alanine aminotransferase, and albumin. We conducted survey-weighted linear regression adjusted for covariates to examine associations between fluoride exposure and kidney or liver function. Adolescent participants were 15 years old and adults were 24 years old on average. The median (IQR) UF concentration among adolescents was 0.48 (0.48) mg/L. Approximately 74% of adolescents and 70% of adults had DF with varying degrees of severity (ranging from very mild to severe). Each 1 mg/L increase in UF was associated with an approximately 5 mL/min/1.73 m² lower eGFR among adolescents (B = -4.73, 95% CI: -8.35, -1.12, p = 0.010). Higher UF was also associated with higher serum uric acid (mg/dl) (B = 0.17, 95% CI: 0.01, 0.33, p = 0.040) among adolescents. DF was associated with lower eGFR among adolescents (B = -3.72, 95% CI: -7.10, -0.33, p = 0.031) and adults (B = -3.90, 95% CI: -6.49, -1.31, p = 0.003). In addition, having DF was negatively associated with BUN among adolescents (B = -0.83, 95% CI: -1.44, -0.22, p = 0.007). No other significant associations were observed for liver markers. Chronic fluoride exposure during tooth development and recent fluoride exposure in adolescence are cross-sectionally associated with a lower rate of kidney filtration among adolescents and young adults in the US. Prospective US-based studies are needed to determine whether these associations are causal.

Prenatal fluoride exposure, at United States (US) population relevant levels, has been associated with poorer child neurodevelopmental outcomes; however, no US study has examined whether these associations manifest in infancy. This study investigated associations between prenatal fluoride exposure and infants' neurodevelopment in Los Angeles, California. Participants were from the Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) cohort. MADRES is a predominately Hispanic prospective pregnancy and birth cohort in urban Los Angeles. Third trimester specific gravity-adjusted maternal urinary fluoride (MUF_SG) concentration was a biomarker of fluoride exposure. Infant motor development, problem solving, communication and personal-social functioning at 6, 9, 12, and 18-months were assessed with the Ages and Stages Questionnaire-3 (ASQ-3). ASQ-3 scores were reverse coded, such that higher scores indicate worse performance. Longitudinal negative binomial regression examined associations between MUF_SG and ASQ-3 scores adjusted for maternal age, race/ethnicity, income, BMI, infant sex and corrected infant age at ASQ-3 assessment. Among 346 mother-child pairs, the median (IQR) MUF_SG was 0.79 (0.54-1.07) mg/L. Higher MUF_SG was associated with worse gross motor performance (IRR=1.22, 95% CI: 1.03-1.45, p=0.02). No significant associations were observed between MUF_SG and fine motor: IRR=1.15 (95% CI: 0.96-1.39), problem solving: IRR=1.15 (95% CI: 0.90-1.48), personal-social: IRR=1.04 (95% CI: 0.83-1.31), or communication: IRR=0.90 (95% CI: 0.71-1.14) scores. Third trimester fluoride exposure may increase risk of developmental neurotoxicity manifesting in infancy. Additional studies are needed to further explore this association across other US-based regions and the nation.