PICO Search Assignment Worksheet                Name: Christina Shamrock

Brief description of patient problem/setting (summarize the case very briefly)

A 35 y/o woman came to her Family medicine doctor and brought her 4 y/o son who is being observed for a developmental delay. Her family has recently immigrated from China. She is wondering if the fluoride added to the drinking water possibly caused and continues to influence her child’s neurocognitive development delay and considering installing a water filter.

Search Question: Does fluoride added to drinking water cause neurocognitive development delay and lowered IQ levels in pediatric population of 4 years old?

Question Type: What kind of question is this?

☐Prevalence                  ☐Screening          ☐Diagnosis

☐Prognosis                    ☐Treatment          ☒Harms

Assuming that the highest level of evidence to answer your question will be meta-analysis or systematic review, what other types of study might you include if these are not available (or if there is a much more current study of another type)?
Please explain your choices.

Harms: Syst. Rev>RCT>Cohort>Case Control>Case series

A randomized controlled trial with a significant N number would be a next best choice to answer my question.  However, since it’s about Harms, it would be ethically difficult to set up an RCT. Therefore, I will consider Retrospective/Prospective and cross sectional studies. I will attempt finding evidence for specific population – pediatric patients 4 years old (+/- 2 years). However, if I don’t find literature with strong evidence level to answer my question for that population, I will track back to general pediatric population. While my patient currently resides in the US, she had recently immigrated from China – a country known for it’s high water fluoridation levels, so evidence found in China may also be applicable.

I would also consider a Cohort study with a significant N number if it addresses a specific population I am looking into – children 4 years old.

PICO search terms:

P	I	C	O
Pediatric Population	Fluoride	Fluoride free drinking water	Cognitive disorder
Pregnant women	Fluoridation	Low fluoride levels in drinking water	Intellectual disability
Children 4 years old (+/- 2 years)	Fluoridated drinking water		Neurotoxic disorder
	High fluoride regions	Low fluoride regions	IQ Level

Search tools and strategy used:

Please indicate what data bases/tools you used, provide a list of the terms you searched together in each tool, and how many articles were returned using those terms and filters.
Explain how you narrow your choices to the few selected articles.

Results Found

Pub Med :

• Search words: Cognitive disorder, Dental caries, Drinking water, Fluoridation, Fluoride poisoning, Intellectual disability, Neurotoxic disorder, Prenatal exposure delayed effects
• Filter “published between 2016 and now”
• 68 results

TRIP:

• Search words: Cognitive disorder, Dental caries, Drinking water, Fluoridation, Fluoride poisoning, Intellectual disability, Neurotoxic disorder, Prenatal exposure delayed effects
• 29 results
• However, no systematic reviews or RCTs

JAMA:

• Search words: Cognitive disorder, Dental caries, Drinking water, Fluoridation, Fluoride poisoning, Intellectual disability, Neurotoxic disorder, Prenatal exposure delayed effects
• 7 results but no systematic reviews or RCTs

Science Direct:

• Search words: Cognitive disorder, Dental caries, Drinking water, Fluoridation, Fluoride poisoning, Intellectual disability, Neurotoxic disorder, Prenatal exposure delayed effects
• 4 results
• 1 result after checking boxes “2021” and “2020”

Google Scholar:

• Search words: Cognitive disorder, Dental caries, Drinking water, Fluoridation, Fluoride poisoning, Intellectual disability, Neurotoxic disorder, Prenatal exposure delayed effects
• 232 results
• Filter “Since 2017” applied
• 73 Results

I narrowed by choices by focusing on articles that answer my clinical question as close as possible and attempted to gather the highest level of evidence. I included 2 meta-analyses, a prospective cohort study that focuses on pediatric population of 3 to 4 years old and a recent (2020) cross sectional study conducted in China.

Name: Developmental Fluoride Neurotoxicity: A Systematic Review and Meta-Analysis Citation: Choi AL, Sun G, Zhang Y, Grandjean P. Developmental fluoride neurotoxicity: a systematic review and meta-analysis. Environ Health Perspect. 2012;120(10):1362-1368. doi:10.1289/ehp.1104912

Type of Article: Systematic review and meta-analysis

Background: Although fluoride may cause neurotoxicity in animal models and acute fluoride poisoning causes neurotoxicity in adults, very little is known of its effects on children’s neurodevelopment. Objective: We performed a systematic review and meta-analysis of published studies to investigate the effects of increased fluoride exposure and delayed neurobehavioral development. Methods: We searched the MEDLINE, EMBASE, Water Resources Abstracts, and TOXNET databases through 2011 for eligible studies. We also searched the China National Knowledge Infrastructure (CNKI) database, because many studies on fluoride neurotoxicity have been published in Chinese journals only. In total, we identified 27 eligible epidemiological studies with high and reference exposures, end points of IQ scores, or related cognitive function measures with means and variances for the two exposure groups. Using random-effects models, we estimated the standardized mean difference between exposed and reference groups across all studies. We conducted sensitivity analyses restricted to studies using the same outcome assessment and having drinking-water fluoride as the only exposure. We performed the Cochran test for heterogeneity between studies, Begg’s funnel plot, and Egger test to assess publication bias, and conducted meta-regressions to explore sources of variation in mean differences among the studies. Results: The standardized weighted mean difference in IQ score between exposed and reference populations was –0.45 (95% confidence interval: –0.56, –0.35) using a random-effects model. Thus, children in high-fluoride areas had significantly lower IQ scores than those who lived in low-fluoride areas. Subgroup and sensitivity analyses also indicated inverse associations, although the substantial heterogeneity did not appear to decrease. Conclusions: The results support the possibility of an adverse effect of high fluoride exposure on children’s neurodevelopment. Future research should include detailed individual-level information on prenatal exposure, neurobehavioral performance, and covariates for adjustment.

Key Points Of the 39 studies identified, the authors considered 27 to be eligible. Choi et al. reported a mean difference in IQ (intelligence quotient) score between exposed and reference populations of –0.4 (95% confidence interval: –0.5, –0.3) using a random-effects model. Thus, children in high-fluoride areas had significantly lower IQ scores than those who lived in low-fluoride areas.

Why I chose it This is the classical meta analysis that is being cited in countless literature sources I’ve encountered that were published before 2019. Therefore, I thought it would be useful for us to familiarize ourselves with it.

Hyperlink & PDF https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3491930/

Name: Developmental fluoride neurotoxicity: an updated review Citation: Grandjean, P. Developmental fluoride neurotoxicity: an updated review. Environ Health 18, 110 (2019). https://doi.org/10.1186/s12940-019-0551-x

Type of Article: Systematic review

Abstract Background: After the discovery of fluoride as a caries-preventing agent in the mid-twentieth century, fluoridation of community water has become a widespread intervention, sometimes hailed as a mainstay of modern public health. However, this practice results in elevated fluoride intake and has become controversial for two reasons. First, topical fluoride application in the oral cavity appears to be a more direct and appropriate means of preventing caries. Second, systemic fluoride uptake is suspected of causing adverse effects, in particular neurotoxicity during early development. The latter is supported by experimental neurotoxicity findings and toxicokinetic evidence of fluoride passing into the brain. Method: An integrated literature review was conducted on fluoride exposure and intellectual disability, with a main focus on studies on children published subsequent to a meta-analysis from 2012. Results: Fourteen recent cross-sectional studies from endemic areas with naturally high fluoride concentrations in groundwater supported the previous findings of cognitive deficits in children with elevated fluoride exposures. Three recent prospective studies from Mexico and Canada with individual exposure data showed that early-life exposures were negatively associated with children’s performance on cognitive tests. Neurotoxicity appeared to be dose-dependent, and tentative benchmark dose calculations suggest that safe exposures are likely to be below currently accepted or recommended fluoride concentrations in drinking water.

Key Points After attempts to dispute clinical significance of Choi et al study have been made, a newer meta-analysis on the subject was conducted.  The results support the notion that elevated fluoride intake during early development can result in IQ deficits that may be considerable. Recognition of neurotoxic risks is necessary when determining the safety of fluoride-contaminated drinking water and fluoride uses for preventive dentistry purposes

Hyperlink & PDF https://ehjournal.biomedcentral.com/articles/10.1186/s12940-019-0551-x

Why I chose it This updated review is a newer study that builds up on the classical Choi et al meta-analysis confirming its findings and is so far the most up to date systematic review on my topic.

Name: Association Between Maternal Fluoride Exposure During Pregnancy and IQ Scores in Offspring in Canada Citation: Green R, Lanphear B, Hornung R, Flora D, Martinez-Mier EA, Neufeld R, Ayotte P, Muckle G, Till C. Association Between Maternal Fluoride Exposure During Pregnancy and IQ Scores in Offspring in Canada. JAMA Pediatr. 2019 Aug 19;173(10):940–8. doi: 10.1001/jamapediatrics.2019.1729. Epub ahead of print. PMID: 31424532; PMCID: PMC6704756.

Type of Article: Prospective Cohort Study

Abstract Importance: The potential neurotoxicity associated with exposure to fluoride, which has generated controversy about community water fluoridation, remains unclear. Objective: To examine the association between fluoride exposure during pregnancy and IQ scores in a prospective birth cohort. Design, setting, and participants: This prospective, multicenter birth cohort study used information from the Maternal-Infant Research on Environmental Chemicals cohort. Children were born between 2008 and 2012; 41% lived in communities supplied with fluoridated municipal water. The study sample included 601 mother-child pairs recruited from 6 major cities in Canada; children were between ages 3 and 4 years at testing. Data were analyzed between March 2017 and January 2019. Exposures: Maternal urinary fluoride (MUFSG), adjusted for specific gravity and averaged across 3 trimesters available for 512 pregnant women, as well as self-reported maternal daily fluoride intake from water and beverage consumption available for 400 pregnant women. Main outcomes and measures: Children’s IQ was assessed at ages 3 to 4 years using the Wechsler Primary and Preschool Scale of Intelligence-III. Multiple linear regression analyses were used to examine covariate-adjusted associations between each fluoride exposure measure and IQ score. Results: Of 512 mother-child pairs, the mean (SD) age for enrollment for mothers was 32.3 (5.1) years, 463 (90%) were white, and 264 children (52%) were female. Data on MUFSG concentrations, IQ scores, and complete covariates were available for 512 mother-child pairs; data on maternal fluoride intake and children’s IQ were available for 400 of 601 mother-child pairs. Women living in areas with fluoridated tap water (n = 141) compared with nonfluoridated water (n = 228) had significantly higher mean (SD) MUFSG concentrations (0.69 [0.42] mg/L vs 0.40 [0.27] mg/L; P = .001; to convert to millimoles per liter, multiply by 0.05263) and fluoride intake levels (0.93 [0.43] vs 0.30 [0.26] mg of fluoride per day; P = .001). Children had mean (SD) Full Scale IQ scores of 107.16 (13.26), range 52-143, with girls showing significantly higher mean (SD) scores than boys: 109.56 (11.96) vs 104.61 (14.09); P = .001. There was a significant interaction (P = .02) between child sex and MUFSG (6.89; 95% CI, 0.96-12.82) indicating a differential association between boys and girls. A 1-mg/L increase in MUFSG was associated with a 4.49-point lower IQ score (95% CI, -8.38 to -0.60) in boys, but there was no statistically significant association with IQ scores in girls (B = 2.40; 95% CI, -2.53 to 7.33). A 1-mg higher daily intake of fluoride among pregnant women was associated with a 3.66 lower IQ score (95% CI, -7.16 to -0.14) in boys and girls.

Key Points In this prospective birth cohort study from 6 cities in Canada, higher levels of fluoride exposure during pregnancy were associated with lower IQ scores in children measured at age 3 to 4 years. These findings were observed at fluoride levels typically found in white North American women. This indicates the possible need to reduce fluoride intake during pregnancy.

Why I chose it While this article looks at a population sample from Canada, it addresses specifically pediatric population of 3-4 years old and it was published only 2 years ago so I decided to include it.

Hyperlink & PDF https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6704756/

Name: Fluoride exposure and intelligence in school-age children: evidence from different windows of exposure susceptibility Citation: Xu, K., An, N., Huang, H. et al. Fluoride exposure and intelligence in school-age children: evidence from different windows of exposure susceptibility. BMC Public Health 20, 1657 (2020). https://doi.org/10.1186/s12889-020-09765-4

Type of Article: Cross sectional Study

Abstract: Background The intellectual loss induced by fluoride exposure has been extensively studied, but the association between fluoride exposure in different susceptibility windows and children’s intelligence is rarely reported. Hence, we conducted a cross-sectional study to explore the association between fluoride exposure in prenatal and childhood periods and intelligence quotient (IQ). Methods We recruited 633 local children aged 7–13 years old randomly from four primary schools in Kaifeng, China in 2017. The children were divided into four groups, of which included: control group (CG, n = 228), only prenatal excessive fluoride exposure group (PFG, n = 107), only childhood excessive fluoride exposure group (CFG, n = 157), both prenatal and childhood excessive fluoride exposure group (BFG, n = 141). The concentrations of urinary fluoride (UF) and urinary creatinine (UCr) were determined by fluoride ion-selective electrode assay and a creatinine assay kit (picric acid method), respectively. The concentration of UCr-adjusted urinary fluoride (CUF) was calculated. IQ score was assessed using the second revision of the Combined Raven’s Test-The Rural in China (CRT-RC2). Threshold and saturation effects analysis, multiple linear regression analysis and logistic regression analysis were conducted to analyze the association between fluoride exposure and IQ. Results The mean IQ score in PFG was respectively lower than those in CG, CFG and BFG (P < 0.05). The odds of developing excellent intelligence among children in PFG decreased by 51.1% compared with children in CG (OR = 0.489, 95% CI: 0.279, 0.858). For all the children, CUF concentration of ≥1.7 mg/L was negatively associated with IQ scores (β = − 4.965, 95% CI: − 9.198, − 0.732, P = 0.022). In children without prenatal fluoride exposure, every 1.0 mg/L increment in the CUF concentration of ≥2.1 mg/L was related to a reduction of 11.4 points in children’s IQ scores (95% CI: − 19.2, − 3.5, P = 0.005)

633 local children aged 7-13 years recruited randomly from four primary schools in Kaifeng, China in 2017.The concentrations of urinary fluoride and urinary creatinine were determined by fluoride ion-selective electrode assay and a creatinine assay kit (picric acid method), respectively. Adjusting for children’s age, gender, gestational weeks, parental education levels and children’s BMI was made.Conclusions: Prenatal and childhood excessive fluoride exposures may impair the intelligence development of school children. Furthermore, children with prenatal fluoride exposure had lower IQ scores than children who were not prenatally exposed; therefore the reduction of IQ scores at higher levels of fluoride exposure in childhood does not become that evident.

Why I chose it: While my patient currently resides in the US, she had recently immigrated from China – a country known for it’s high water fluoridation levelsThe study used randomization in participant selection and adjusted for children’s age, gender, gestational weeks, parental education levels and children’s BMI.

Hyperlink & PDF: https://bmcpublichealth.biomedcentral.com/articles/10.1186/s12889-020-09765-4

Summary of Evidence:

Author/Date	Level of Evidence	Sample/Setting   (# of subjects/ studies, cohort definition etc. )	Outcomes Studied	Key Findings	Limitations and Biases
Choi et al., 2012   Developmental fluoride neurotoxicity: a systematic review and meta-analysis.	Systematic review and meta-analysis	27 studies were chosen for this report. The criteria for inclusion of studies included studies with high and reference fluoride exposures, end points of IQ scores or other related cognitive function measures, presentation of a mean outcome measure, and associated measure of variance (95% confidence intervals) and numbers of participants.	Differences in IQ	Choi et al. reported a mean difference in IQ (intelligence quotient) score between exposed and reference populations of –0.4 (95% confidence interval: –0.5, –0.3) using a random-effects model. Thus, children in high-fluoride areas had significantly lower IQ scores than those who lived in low-fluoride areas.	As an article by Jeckel et al., 2007 well pointed out, even if we ignore the weaknesses of the study, including a lack of individual-level information and the high probability of confounding because the authors did not adjust for covariates, a difference of 0.4 in mean IQ is clinically negligible even though it was statistically significant. In general, clinical importance takes priority over statistical significance. The p-value can easily change from significant to nonsignificant because of sample size or the mean difference and standard deviation of the variable in the study population. As Choi et al., stated in their conclusion, there is a “possibility of an adverse effect of high fluoride exposure on children’s neurodevelopment.” Such a conclusion can be considered an ecological fallacy, which can easily lead to misinterpretation of the results. It is important to know that statistics cannot provide a simple substitute for clinical judgment 3.
Grandjean et al., 2019   Developmental fluoride neurotoxicity: an updated review	Updated Systematic Review	14 Cross sectional studies were considered eligible for this research. Only studies posted within the past 10 years were used.	IQ loss	Fourteen recent cross-sectional studies from endemic areas with naturally high fluoride concentrations in groundwater supported the previous findings of cognitive deficits in children with elevated fluoride exposures. Three recent prospective studies from Mexico and Canada with individual exposure data showed that early-life exposures were negatively associated with children’s performance on cognitive tests. Neurotoxicity appeared to be dose-dependent, and tentative benchmark dose calculations suggest that safe exposures are likely to be below currently accepted or recommended fluoride concentrations in drinking water	Even though this meta analysis results may be considered valid from the statistical standpoint, there is room left for doubt when applying this information in terms of clinical significance. Authors did a good job finding evidence of a correlation between high water fluoridation and IQ loss in theory. However, many other confounders such as socioeconomic status of parents, environmental exposure to other pollutants that may influence IQ (Mercury, lead or arsenic for example) have to be considered if we were to draw conclusions significant enough to influence health policy in the United States.
Green et al., 2019   Association Between Maternal Fluoride Exposure During Pregnancy and IQ Scores in Offspring in Canada	Prospective Birth Cohort	512 mother-child pairs were selected from 6 different cities across Canada. Participants were not recruited if there was a known fetal abnormality, if they had any medical complications, or if there was illicit drug use during pregnancy Children age 3 to 4 years were included. Covarities such as established factors associated with fluoride metabolism, children’s intellectual abilities, mother’s race/ethnicity/education were considered and the adjustments for covarities have been made. Adjusting for lead, mercury, manganese, perfluorooctanoic acid, or arsenic concentrations was done.	Maternal fluoride intake and children’s IQ	In this prospective birth cohort study from 6 cities in Canada, higher levels of fluoride exposure during pregnancy were associated with lower IQ scores in children measured at age 3 to 4 years.   These findings were observed at fluoride levels typically found in white North American women. This indicates the possible need to reduce fluoride intake during pregnancy.	Although higher maternal ingestion of fluoride corresponds to higher fetal plasma fluoride levels, even serial maternal urinary spot samples may not precisely represent fetal exposure throughout pregnancy. Also, while this analysis controlled for a comprehensive set of covariates, they did not include maternal IQ data. Fluoride intake estimate only considered fluoride from beverages; it did not include fluoride from other sources such as dental products or food. Moreover, a greater proportion of women living in fluoridated communities (124 [76%]) had a university-level degree compared with women living in nonfluoridated communities (158 [66%]) Also, this study did not include assessment of postnatal fluoride exposure or consumption which allows room for significant confounding.
Kaihong Xu et al., 2020   Fluoride exposure and intelligence in school-age children: evidence from different windows of exposure susceptibility	Cross sectional study	633 local children aged 7-13 years recruited randomly from four primary schools in Kaifeng, China in 2017. The concentrations of urinary fluoride and urinary creatinine were determined by fluoride ion-selective electrode assay and a creatinine assay kit (picric acid method), respectively. adjusting for children’s age, gender, gestational weeks, parental education levels and children’s BMI was made.	Mean IQ score	Prenatal and childhood exposure to excessive fluoride may impair the intelligence development of school children. Furthermore, children with prenatal fluoride exposure had lower IQ scores than children who were not prenatally exposed; therefore the reduction of IQ scores at higher levels of fluoride exposure in childhood does not become that evident. The results support the necessary restriction of fluoride intake for pregnant women and school-age children to protect children’s intellectual development.	Firstly, urine samples were collected in the morning, not 24 h Secondly, considering the influence of urine dilution on UF (Urine Fluoride), UCr was used to adjust the UF. However, due to the instability of UCr in growing children or experiencing puberty, this may also be one of the limitations. Also, the project was a cross-sectional study which lasted 1 month, and only one-time sampling was conducted, and so the inferential causality was weak even for statistical significance, let along clinical significance. Long term large-scale epidemiological studies should be conducted to provide more abundant evidence.

Conclusions:

1 – Choi et al., 2012, after analyzing 27 carefully selected studies, reported a mean difference in IQ (intelligence quotient) score between exposed and reference populations of –0.4 (95% confidence interval: –0.5, –0.3) using a random-effects model. Thus, children in high-fluoride areas had significantly lower IQ scores than those who lived in low-fluoride areas. However, the study had it’s limitations (see Evidence Summary table)

2  – An updated review of developmental fluoride neurotoxicity by Philippe Grandjean, published in Environmental Health on December 19, 2019, after analyzing 14 additional cross sectional studies posted within the past 10 years, concluded that recent epidemiological studies results results support the notion that elevated fluoride intake during early development can result in IQ deficits that may be considerable. He noted that the recognition of neurotoxic risks is necessary when determining the safety of fluoride contaminated drinking water and fluoride uses for preventive dentistry purposes⁴.

3 – The study used mother’s urinary fluoride levels measured each trimester of mother’s pregnancy and complete covariate date as the first measure of outcomes.

Second measure of outcomes was chosen as drinking tap water. After a thorough exclusion and adjustments the conclusions have been drawn that higher levels of fluoride exposure during pregnancy were associated with lower IQ scores in children measured at age 3 to 4 years.

4 – Prenatal and childhood excessive fluoride exposures may impair the intelligence development of school children. Furthermore, children with prenatal fluoride exposure had lower IQ scores than children who were not prenatally exposed; therefore the reduction of IQ scores at higher levels of fluoride exposure in childhood does not become that evident.

Overall conclusion

Multiple studies performed in different countries attempted to establish an inverse correlation between children’s IQ and prenatal/postnatal fluoride exposure. Overall the statistical data proving the correlation is there. However, when it comes to assigning clinical significance, there’s a need to take a look at a broader picture. While some studies did a broad exposure analysis, they failed accounting for important confounders. Others were more thorough when it came to confounding factors, but they only looked at the prenatal Fluoride exposure.

Clinical “bottom line”

Weight of evidence

Opportunities for epidemiological studies of the general population depend on the existence of comparable groups exposed to different and stable amounts of fluoride, e.g., from drinking water. Such circumstances are difficult to find in many industrialized countries, as water-fluoride concentrations may not be well defined, residents may consume beverages from a variety of sources, and exposures are affected by residences changing over time. Multiple epidemiological studies of developmental fluoride neurotoxicity have been conducted in countries such as China where elevated water-fluoride concentrations may exceed 1 mg/L in many rural communities. In these settings, families typically remain at the same residence, with a well-defined water source that has provided fairly constant fluoride exposures (Grandjean et al.).

    Two meta-analyses conducted in different points in time (Choi et al, 2012and Granjdean et al., 2019) arrived at the same conclusion – existence of an inverse relationship between children’s IQ levels and fluoride exposure. However, they did not adjust for important confounders such as the socioeconomic status of parents and environmental exposure to other pollutants that may influence IQ (Mercury, lead or arsenic for example).

    Granjdeen, 2019, anchored his conclusion on data from high-fluoride endemic areas in China (which were the majority of studies included in his meta-analysis). These studies have reported on abnormal neuropathology findings from aborted fetuses and lower nerve cell numbers and volumes in fetal brain tissue at the elevated exposures. Deviations observed in neurotransmitters and receptors have suggested neural dysplasia, as later replicated along with decreased excitatory aspartic acid and elevated inhibitory taurine in comparison to controls. Although these studies are in agreement with the notion that fluoride from the mother’s circulation can pass into the fetal brain with subsequent anatomic and biochemical changes, the studies related to elevated fluoride exposure originate primarily from coal burning, which may have contributed other, undocumented contaminants. (Granjdeen, 2019)

     A prospective birth cohort study conducted in Canada (Green et al., 2019) represented my population the best – children aged 3 to 4 years. However, it only focused on prenatal fluoride exposure and, therefore, left room for significant confounding such as postnatal Fluoride and other pollutant exposure.

     A recent (2020) cross sectional study performed in China also found causality between fluoride exposure in utero and after birth, and the IQ levels. However, it only lasted 1 month, and only one-time sampling was conducted, and so the inferential causality was weak.

Long term large-scale epidemiological studies should be conducted to provide more abundant evidence.

Magnitude of any effects

The relationship between neurocognitive development and Fluoride exposure is still being understood. With every study conducted we gain more understanding of nature of this relationship as well as what kind of information needed to assign a clinical significance to the results.

Clinical significance

Overall, the statistical evidence on an inverse relationship between children’s IQ levels and fluoride exposure is there. However, it is hard to assign a clinical significance to it that would create room for changes in health policy revision due to massive confounding. The meta analyses (Choi et al, 2012, and Granjdean et al., 2019) did not account for parental socioeconomic status and other environmental toxin exposure that may affect neurocognitive development. Canadian study (Green et al., 2019) only looks at the prenatal Fluoride exposure, and the most recent cross sectional study based it’s evidence on only one sample collection.

Other considerations:

In 1991, the Centers for Disease Control (CDC) in the USA measured fluoride levels and found that where water is fluoridated between 0.7 and 1.2 ppm overall fluoride, total fluoride intake for adults was between 1.58 and 6.6 mg per day while for children it was between 0.9 and 3.6 mg per day and that there was at least a sixfold variation just from water consumption alone⁵. Therefore, obtaining reliable data from any prospective studies would be extremely difficult due to the variety of sources of Fluoride exposure and variety of ways the body metabolizes it resulting in different levels of the element in the system. The best way to obtain results that may have clinical significance would be to set up a prospective Long term large-scale epidemiological study with a significant N number that accounts for important confounders such as additional sources of Fluoride exposure, parent’s socioeconomic status, maternal IQ, age, and perinatal care.

3 –  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3621182/

4 – https://fluoridealert.org/studytracker/37478/

5 – https://www.cdc.gov/fluoridation/guidelines/cdc-statement-on-community-water-fluoridation.html