Table 2.

Characteristics of the studies included in the review.

Reference	Country	Study Type	Aim of the Study	Population	Number of Samples	Fluoride Exposure Method	Average Fluoride Levels	ADHD Assessment	Main Findings	Adjustment Factors
Bashash et al., 2018 [43]	Mexico	Cohort study (ELEMENT project)	To assess the relation between prenatal exposure to fluoride and ADHD	Mother-child pairs	210	Maternal Urinary fluoride adjusted for creatinine (MUFcr)	The overall mean level of MUFcr averaged across all trimesters was 0.85 mg/L, with an Interquartile Range (IQR) of 0.46 mg/L	CRS-R or CPT-II or DSM-IV Hyperactivity-Impulsivity scale, DSM-IV ADHD scale, DSM-IV Inattention scale	Association between MUFcr and CRS-R for DSM-IV Inattention and Cognitive problems and inattention, not hyperactivity or impulse control	Smoking, maternal education, child sex, HOME score, exposure to other contaminants
Malin and Till 2015 [44]; Perrott 2018 [45]	USA	Cross-sectional ecological survey [National Survey of Children’s Health (2003, 2007, 2011)]	To examine the relation between exposure to fluoridated water and ADHD prevalence among children and adolescents	Children aged 4–17	2003: 79,264 2007: 73,123 2011: 76,015	Centers for Disease Control and Prevention (CDC) website provide data on the number of people receiving fluoridated water from public water supplies in each of America’s 50 states	-	Parent reported health care provider-diagnosed ADHD	Prevalence of ADHD increased from 7.8% in 2003 to 11% in 2011. Water fluoridation prevalence was positively associated with ADHD. The association between water fluoride exposure and ADHD incidence disappears once elevation is included in the multiple regression analysis.	Socioeconomic status in the first report and mean state elevation, median household income, smoking prevalence 2013, water fluoridation in 1992, obese youth average 2003–2004, longitude, home ownership, per capita personal income 2009, low birth rate 2005, bachelor’s degree 2000, age over 65 in the fully adjusted model
Riddell et al., 2019 [42]	Canada	Cross-sectional survey [Canadian Health Measures Survey (Cycles 2 and 3)]	To examine the relation between urinary and tap water fluoride concentration and attention-related outcomes	Children aged 6–17	1877 UF 1722 Community Water Fluoridation (CWF) status 980 tap water sample	Urinary fluoridation (UF), city fluoridation status, tap water fluoride	The mean urinary fluoride adjusted for specific gravity (UFSG) concentration was 0.61 mg/L among the 1877 youths from Cycles 2 and 3	ADHD diagnosis SDQ Hyperactivity-inattention subscale	Children exposed to higher tap water fluoride levels had a higher risk of receiving an ADHD diagnosis. UF levels were not associated with ADHD or symptom-related	Sex, age, ethnicity, BMI, level of parental education, household income, cigarette smoke exposure, blood lead level
Adkins et al., 2022 [46]	USA	Cross-sectional study [CCAAPS]	To examine the association between UF and internalizing symptoms among adolescents, also evaluating sex differences	Adolescents	334	UF	UF concentrations at Age-12 visit was 0.88 (0.36) mg/L	Parent reported BASC-2 scale	UF concentration are positively associated with internalizing behaviors, particularly somatization.	Race, sex, age, total family income at age-12 visit, maternal depression, serum cotinine, PRQ relational frustration
Wang et al., 2022 [47]	China	Cross-sectional study	To investigate the relation between fluoride exposure and behavioral outcomes among children	Primary schools’ children	325	UF	The mean ± SD levels of UF was 1.54 ± 0.89 mg/L	CPRS-48 (ADHD Index)	UF associated with psychosomatic problems, no correlation with ADHD	Age, BMI, urinary creatinine, sex, parents migrated
Barberio et al., 2017 [48]	Canada	Cross-sectional survey [Canadian Health Measures Survey]	To examine the association between fluoride exposure and learning disabilities.	Children aged 3–12	Cycle 2 = 1120 Cycle 3 = 1101	UF, creatinine-adjusted urinary fluoride, gravity-adjusted urinary fluoride, tap water sample	UFSG Cycle 2 fluoride subsample: 37.78 µmol/L Cycle 2 constrained fluoride subsample = 43.46 µmol/L Cycle 3 fluoride subsample: 34.25 µmol/L Cycle 3 constrained fluoride subsample: 40.71 µmol/L	Response to items of the survey	No association between UF and learning disabilities and ADHD diagnosis.	Sex, age, household education, household income adequacy
Khairkar et al., 2021 [49]	India	Case–control study (Letter to editor)	To analyze the outcome of spectral severity of water fluoride levels in adolescents on their neurocognitive and neuropsychiatric disorders	Adolescents aged 11–15	150	Level of fluoride in community water	-	Not specified	Significant association between fluoride exposure and ADHD, disruptive behaviors, defiant disorder and scholastic arithmetic skill disorders	Not specified

Abbreviations: ADHD: Attention deficit hyperactivity disorder. BMI: body mass index. ELEMENT: Early Life Exposure in Mexico to Environmental Toxicants project. UF: Urinary fluoridation. UFSG: urinary fluoride adjusted for specific gravity. MUF: Maternal Urinary fluoride. MUFcr: Maternal Urinary fluoride adjusted for creatinine. CDC: Centers for Disease Control and Prevention. CRS-R: Conners’ Rating Scales—Revised. CPT-II: Conners’ Continuous Performance Test. DSM-IV: Diagnostic and Statistical Manual of Mental Disorders—4th Edition. CWF: Community Water Fluoridation. CCAAPS: Cincinnati Childhood Allergy and Air pollution study. BASC-2: Behavior Assessment System for Children-2. CPRS-48: Conner’s Parent Reporting Scale-Revised 48.