Fluoride exposure and cognitive neurodevelopment: Systematic review and dose-response meta-analysis

Veneri, Federica; Generali, Luigi; Giannone, Maria Edvige; Mazzoleni, Elena; Birnbaum, Linda S.; Consolo, Ugo; Filippini, Tommaso

doi:10.1016/j.envres.2023.115239

Cited by 36 publications

(16 citation statements)

References 51 publications

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“…Differences in study designs, fluoride exposure measures and methods for diagnosing ADHD may account for the heterogeneity in our results. However, evidence of neurotoxic effects on brain development has been repeatedly supported, particularly in terms of IQ performance [31,32,57,58]. Finally, the low number of studies investigating the association between fluoride exposure and ADHD is a limitation of our review.…”

Section: Discussionmentioning

confidence: 96%

“…Early exposure to fluoride has been associated with impaired cognitive neurodevelopment with low intelligence quotient (IQ). This association has been reported starting at rather low levels of fluoride exposure such as 1 mg/L in water, which can also be detectable in urine at corresponding levels [31,32]. As matter of fact, also the National Toxicology Program (NTP) aimed to explore the relation between fluoride exposure and neurodevelopmental and cognitive health effects in its recent systematic review.…”

Section: Introductionmentioning

confidence: 97%

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Fluoride Exposure and ADHD: A Systematic Review of Epidemiological Studies

et al. 2023

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Background and objectives: Attention deficit hyperactivity disorder (ADHD) is a childhood-onset neurodevelopmental disorder characterized by two dimensions: inattentiveness and hyperactivity/impulsivity. ADHD may be the result of complex interactions between genetic, biological and environmental factors possibly including fluoride exposure. Materials and methods: A literature search was performed on 31 March 2023 in the following databases: PubMed, Embase and Web of Science. We defined the following inclusion criteria according to the PECOS statement: a healthy child and adolescent population (P), fluoride exposure of any type (E), comparison with low or null exposure (C), ADHD spectrum disorder (O), and ecological, cross-sectional, case–control and cohort studies (S). Results: We found eight eligible records corresponding to seven different studies investigating the effect of fluoride exposure on children and adolescents. One study had a cohort design and one a case–control one, while five were cross-sectional. Only three studies applied validated questionnaires for the purpose of ADHD diagnosis. As regards exposure assessment, levels of fluoride in urine and tap water were, respectively used in three and two studies, while two used both. Three studies reported a positive association with ADHD risk, all assessing exposure through fluoride levels. By using urinary fluoride, conversely, a positive correlation with inattention, internalizing symptoms, cognitive and psychosomatic problems was found in three studies, but no relation was found in the other one. Conclusions: The present review suggests that early exposure to fluoride may have neurotoxic effects on neurodevelopment affecting behavioral, cognitive and psychosomatic symptoms related to ADHD diagnosis. However, due to the heterogeneity of the studies included, current evidence does not allow to conclusively confirm that fluoride exposure is specifically linked to ADHD development.

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Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 97%

Fluoride Exposure and ADHD: A Systematic Review of Epidemiological Studies

et al. 2023

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“…3,4 Fluoride can also naturally occur in soil and rock or be released into the environment via industrial processes. 5,6 It is widely established that exposure to high fluoride levels can adversely affect neurodevelopment 7 ; however, findings from recent studies conducted in Mexico and Canada [8][9][10][11] suggest that fluoride exposure at lower US-relevant levels may also be associated with poorer neurodevelopment. Specifically, higher prenatal fluoride exposure in Canada and/or Mexico has been associated with lower IQ among children aged 3 to 4 years in Canada 10 and children aged 6 to 12 years in Mexico, 9 increased symptoms of attention-deficit/hyperactivity disorder (ADHD) among children aged 6 to 12 years, 12 poorer executive function among children aged 3 to 5 years, 13 and poorer performance on measures of global cognition among 12-and 24-month-old boys.…”

Section: Introductionmentioning

confidence: 99%

Maternal Urinary Fluoride and Child Neurobehavior at Age 36 Months

Malin,

Eckel,

et al. 2024

JAMA Netw Open

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ImportanceRecent 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.ObjectiveTo examine associations of third trimester maternal urinary fluoride (MUF) with child neurobehavior at age 3 years in the US.Design, Setting, and ParticipantsThis 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.ExposureSpecific gravity-adjusted MUF (MUFSG), a biomarker of prenatal fluoride exposure.Main Outcomes and MeasuresNeurobehavior 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.ResultsA 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 MUFSG measured were included in the study. Median (IQR) MUFSG 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 MUFSG 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 RelevanceIn 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.

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“…For example, in Portugal, the concentration can reach as high as 14 mg/L, while in Bulgaria, it can be as high as 5 mg/L, and in France, it reaches approximately 8.5 mg/L [20]. Regular consumption of water with high F concentrations, as mentioned earlier, can significantly increase the risk of DF in children [10,21].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Fluoride Concentration in Commercially Available Bottled Water in Romania—A Potential Risk Factor for Dental Fluorosis

et al. 2023

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Fluoride (F) ions actively participate in the dental enamel remineralisation process and inhibit the activity of cariogenic bacteria of the oral biofilm. However, increased systemic intake of F during critical periods of amelogenesis can lead to dental fluorosis (DF). The necessity of our study stemmed from the growing consumption of bottled water, as water is one of the primary sources of F in humans, and labelling F concentration is optional. Our aim was to evaluate the F concentration in bottled natural mineral or spring still waters available on the market in Iasi, Romania. We purchased forty different brands of still bottled water from the major grocery stores and tested them using an ion-selective electrode method. The reliability of the data was assessed by the intraclass correlation coefficient (ICC), while the differences between the obtained and labelled F values were examined using a paired samples t-test. The tested F levels ranged between 0.0338 and 4.6262 milligrams per litter (mg/L). The majority of the samples, around 85% recorded F values ranging from 0.232 to 0.0338 mg/L, offering slight or no benefit in caries prevention. Another 10% of the samples had F values ranging between 0.3 and 0.4 mg/L and could provide a dental health benefit. A percentage of 5% of the tested samples recorded F levels above the optimal level of 0.7 mg/L, as set by the American Dental Association (ADA) and the United States Department of Health and Human Services (U.S. HHS). This elevated F concentration poses a potential risk for DF in infants and toddlers, indicating that regular consumption of these samples may be unsafe.

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Fluoride exposure and cognitive neurodevelopment: Systematic review and dose-response meta-analysis

Cited by 36 publications

References 51 publications

Fluoride Exposure and ADHD: A Systematic Review of Epidemiological Studies

Fluoride Exposure and ADHD: A Systematic Review of Epidemiological Studies

Maternal Urinary Fluoride and Child Neurobehavior at Age 36 Months

Evaluation of Fluoride Concentration in Commercially Available Bottled Water in Romania—A Potential Risk Factor for Dental Fluorosis

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