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FL: Fluoride and the Brain (2010)

Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:

To study the effects of arsenic and fluoride exposure on children’s intelligence and growth.

Inclusion Criteria:
  • Water containing arsenic and fluoride were used to identify nine villages as target areas for recruitment
  • Children, eight- to 12-year-old age group
  • Children attending school
  • Rural areas.

 

Exclusion Criteria:

Non-consent and not living in the surveyed areas.

Description of Study Protocol:

Recruitment

  • A study of 720 children between eight years and 12 years of age in rural villages in Shanyin county, Shanxi province, China was conducted
  • The children were exposed to arsenic at concentrations of 142μg per L±106μg per L (medium-arsenic group, n=91) and 190μg per L±183μg per L (high-arsenic group, n=180) in drinking water compared with the control group (n=196), which was exposed to low concentrations of arsenic (2±3μg per L) and low concentrations of fluoride (0.5mg per L±0.2mg per L). A study group included children exposed to high concentrations of fluoride (n=253, 8.3mg per L±1.9mg per L) but low concentrations of arsenic (3μg per L±3μg per L).

Design

Cross-sectional study.

Statistical Analysis

  • One-way analysis of variance (ANOVA) was done on the log-transformed data; the Kruskal-Wallis test was also used. Regression ANOVA was used on the log-transformed data.
  • Paired q-test, chi-square test, and T-test were used to compare differences between any of the two study groups
  • Coefficients were calculated using the Spearman rank-order correlation test
  • All values were transformed back to the arithmetic scale for reporting purposes.
Data Collection Summary:

Timing of Measurements

Exposure time in years: Approximately 10 years. 

Dependent Variables

  • IQ
  • Growth and development indicators
  • Age
  • Height
  • Weight
  • Chest circumference
  • Lung capacity.

Independent Variables

  • Water arsenic
  • Water fluoride
  • Urine arsenic
  • Urine fluoride.
Description of Actual Data Sample:

Initial N: 720 children

Attrition (final N): 

Age: 8 and 12 years 

Ethnicity: Asian

Other relevant demographics: Family demographics (e.g., parental age, education, occupation, housing type)

Anthropometrics: Height, weight, chest circumference

Location: Rural villages in Shanyin county, Shanxi province, China.

 

 

Summary of Results:

Results 

  • Children in the control group were taller than those in the high-fluoride group (P<0.05), weighed more than the those in the high-arsenic group (P<0.05) and had higher lung capacity than those in the medium-arsenic group (P<0.05)
  • Children’s growth and development generally showed that exposure to arsenic and fluoride in water had a negative impact, although the effect is neither as striking as the impairment of IQ nor always statistically significant
  • Chest measurements showed the least difference or no statistically significant differences in average rank values among the four groups.

Arsenic

The mean IQ scores decreased from 105±15 for the control group, to 101±16 for the medium-arsenic group (P<0.05), and to 95±17 for the high-arsenic group (P<0.01).

  • Children’s weight in the control group was significantly higher than that in the high-arsenic group (P<0.05)
  • Urinary arsenic concentrations correlated positively with water arsenic concentrations in children in all study groups
  • The Spearman correlation coefficient that was calculated between urinary arsenic concentrations and children’s IQ in the control and high-arsenic groups was –0.201 (P<0.01) and was unadjusted for other factors that may contribute to IQ. This negative correlation suggests that arsenic exposure via water reduces IQ score.

Fluoride

  • The mean IQ score for the high-fluoride group was 101±16 and significantly different from that of the control group (P<0.05).
  • Children’s height in the control group was significantly higher than that in high-fluoride group (P<0.05).
  • Children’s lung capacity in the control group was significantly higher than that in the medium-arsenic group (P<0.05).
  • Urinary fluoride concentrations also correlated positively with water fluoride concentrations in children in all study groups.
  • A Spearman correlation coefficient of –0.107 (P<0.05) was found between urinary fluoride and IQ scores in children in the control and the high-fluoride groups. This negative correlation suggests that fluoride exposure also reduces IQ. These negative correlations between IQ and urinary arsenic and between IQ and urinary fluoride indicate that exposure to high levels of arsenic or fluoride, or both, could affect children’s intelligence.
  • No statistically significant negative correlations were found between IQ and urinary arsenic or between IQ and urinary fluoride in children in the control and medium-arsenic groups.

Distribution of Children Eight Years to 12 Years of Age Based on Intellectual Function

Group
na
Age in years
(mean±SD)
IQ (mean±SD)
Distribution (%)
≤69
70-79
80-89
90-109
110-119
120-129
≥130
High-arsenic
180
9.9±1.5
95.1±16.6*
8.3
9.4
13.3
49.4
15.6
2.8
1.1
Medium-arsenic
91
9.8±1.4
100.6±15.6**
3.3
6.6
11.0
49.5
17.6
9.9
2.2
High-fluoride
253
9.9±1.4
100.5±15.8**
4.0
5.9
12.3
48.2
22.9
4.7
2.0
Control
196
9.9±1.5
104.8±14.7
0
7.7
7.7
44.4
24.5
12.8
3.1
Shanxi
1,274
9.0±0.82
108.0±14.0b
1.3
2.0
5.7
44.8
25.4
16.0
4.7
China
37,288
9.0±0.94
103.5±17.7c
3.6
5.4
10.5
43.1
19.8
12.6
5.0
aNumber of children tested.

bThe average IQ of children in Shanxi was determined to be 108.0±14.0 in 2005, which is statistically different from that of the control group (P<0.01).

cThe average IQ of Chinese children was determined to be 103.5±17.7 in 2005, which is not statistically different from that of the control group (P>0.05).

Significant difference from control group: *P<0.01, **P<0.05.
 

Arsenic (μg/L) and Fluoride (mg/L) Concentrations in Drinking Water and Urine from Subjects in Shanxi Province, China

Group
Water arsenic [n (mean±SD)]
Water fluoride
[n (mean±SD)]
Urinary arsenic
[n (GM±SD)]
Urinary fluoride
[n (GM±SD)]
High-arsenic
50 (190±183)**
[14,502]
50 (0.9±0.5)
[0.3,1.8]
86(73±3)*
[17,595]
73 (1.0±1.7)
[0.2,3.6]
Medium-arsenic
30 (142±106)*
 [7,303) 
30 (1.7±1.1)** [0.5,3.8]
50 (46±3)*
[9,315]
50 (2.8±1.9)* [0.4,6.6]
High-fluoride
21 (3±3)
 [1,10] 
21 (8.3±1.9)** [3.8,11.5]
101 (6±2) [2,20]
106 (5.1±2.0)*
[1.6,11.0]
Control
11 (2±3) [1,10] 
11 (0.5±0.2) [0.2,1.1]
120 (10±2) [3,47]
110 (1.5±1.6) [0.4,3.9]

GM, geometric mean.
Numbers in brackets are lowest and highest observed values.
Significant difference from control group: *P<0.05, **P<0.01.

 

Average Rank of Growth and Development Indicators

Groups
Height
Weight
Chest measurement
Lung capacity
 
n
Average rank
n
Average rank
n
Average rank
n
Average rank
Medium-arsenic  
 
107
399
107
377
106
404
89
294*
High-fluoride
 
278
369*
278
389
278
387
277
343
High-arsenic
 
190
386
190
355*
190
395
108
327
Control
 
205
418*
205
430*
205
380
205
362*

n=Number of children tested.
*Significant difference, P<0.05.

 

Author Conclusion:
  • Children’s intelligence and growth can be affected by high concentrations of arsenic and/or fluoride
  • The IQ scores of the children in the high-arsenic group were the lowest among the four groups
  • High concentrations of arsenic affect children’s intelligence
  • It indicates that arsenic exposure can affect children’s intelligence and growth
  • This study indicates that exposure to fluoride in drinking water is associated with neurotoxic effects in children.
Funding Source:
Government: Shanxi Natural Science Foundation grant 20031093
Reviewer Comments:
  • This study indicates there is a significant effect of arsenic and fluoride on IQ scores and growth and development indicators
  • However, high-arsenic group is showing very low IQ compared with the fluoride group. Sample size in medium-arsenic group is small. The IQ of medium-arsenic group and high-fluoride group had no significant difference based on the mean values. It is not clear whether there is a significant difference of IQ between high-arsenic (95) and high-fluoride (100.5). There is a significant difference between control vs. arsenic and fluoride groups.
  • Further studies are required to assess the effect of arsenic and fluoride on other biological and physiological functions
  • Arsenic and fluoride in urine was a spot sample, not 24-houir urine collection. The calculation is not based on creatinine levels. A standard method of urine collection based on creatinine values is required for any trace element analysis.
  • The study is not randomized and not blinded for the results. Further long-term and short-term exposure studies on arsenic and fluoride are required to study the effects on growth and development. The difference of IQ and development indicators before and after exposure is required for comparison. Other etiological factors and risk factors need to be adjusted.
  • Multivariate analysis was not done, so we cannot get at any possible interaction between arsenic and fluoride exposure, nor can they account for other factors that affect IQ.
Quality Criteria Checklist: Primary Research
Relevance Questions
  1. Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies) N/A
  1. Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies) N/A
  2. Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about? Yes
  2. Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about? Yes
  3. Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice? Yes
  3. Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice? Yes
  4. Is the intervention or procedure feasible? (NA for some epidemiological studies) N/A
  4. Is the intervention or procedure feasible? (NA for some epidemiological studies) N/A
 
Validity Questions
  1. Was the research question clearly stated? Yes
1. Was the research question clearly stated? Yes
  1.1. Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified? Yes
  1.1. Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified? Yes
  1.2. Was (were) the outcome(s) [dependent variable(s)] clearly indicated? Yes
  1.2. Was (were) the outcome(s) [dependent variable(s)] clearly indicated? Yes
  1.3. Were the target population and setting specified? Yes
  1.3. Were the target population and setting specified? Yes
  2. Was the selection of study subjects/patients free from bias? Yes
2. Was the selection of study subjects/patients free from bias? Yes
  2.1. Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study? Yes
  2.1. Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study? Yes
  2.2. Were criteria applied equally to all study groups? Yes
  2.2. Were criteria applied equally to all study groups? Yes
  2.3. Were health, demographics, and other characteristics of subjects described? Yes
  2.3. Were health, demographics, and other characteristics of subjects described? Yes
  2.4. Were the subjects/patients a representative sample of the relevant population? ???
  2.4. Were the subjects/patients a representative sample of the relevant population? ???
  3. Were study groups comparable? Yes
3. Were study groups comparable? Yes
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) Yes
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) Yes
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? N/A
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? N/A
  3.3. Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) Yes
  3.3. Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) Yes
  3.4. If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis? Yes
  3.4. If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis? Yes
  3.5. If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.) Yes
  3.5. If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.) Yes
  3.6. If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")? N/A
  3.6. If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")? N/A
  4. Was method of handling withdrawals described? Yes
4. Was method of handling withdrawals described? Yes
  4.1. Were follow-up methods described and the same for all groups? N/A
  4.1. Were follow-up methods described and the same for all groups? N/A
  4.2. Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.) No
  4.2. Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.) No
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? Yes
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? Yes
  4.4. Were reasons for withdrawals similar across groups? N/A
  4.4. Were reasons for withdrawals similar across groups? N/A
  4.5. If diagnostic test, was decision to perform reference test not dependent on results of test under study? N/A
  4.5. If diagnostic test, was decision to perform reference test not dependent on results of test under study? N/A
  5. Was blinding used to prevent introduction of bias? No
5. Was blinding used to prevent introduction of bias? No
  5.1. In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? N/A
  5.1. In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? N/A
  5.2. Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.) No
  5.2. Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.) No
  5.3. In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? No
  5.3. In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? No
  5.4. In case control study, was case definition explicit and case ascertainment not influenced by exposure status? N/A
  5.4. In case control study, was case definition explicit and case ascertainment not influenced by exposure status? N/A
  5.5. In diagnostic study, were test results blinded to patient history and other test results? N/A
  5.5. In diagnostic study, were test results blinded to patient history and other test results? N/A
  6. Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described? Yes
6. Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described? Yes
  6.1. In RCT or other intervention trial, were protocols described for all regimens studied? N/A
  6.1. In RCT or other intervention trial, were protocols described for all regimens studied? N/A
  6.2. In observational study, were interventions, study settings, and clinicians/provider described? N/A
  6.2. In observational study, were interventions, study settings, and clinicians/provider described? N/A
  6.3. Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect? Yes
  6.3. Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect? Yes
  6.4. Was the amount of exposure and, if relevant, subject/patient compliance measured? Yes
  6.4. Was the amount of exposure and, if relevant, subject/patient compliance measured? Yes
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? N/A
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? N/A
  6.6. Were extra or unplanned treatments described? N/A
  6.6. Were extra or unplanned treatments described? N/A
  6.7. Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups? Yes
  6.7. Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups? Yes
  6.8. In diagnostic study, were details of test administration and replication sufficient? N/A
  6.8. In diagnostic study, were details of test administration and replication sufficient? N/A
  7. Were outcomes clearly defined and the measurements valid and reliable? Yes
7. Were outcomes clearly defined and the measurements valid and reliable? Yes
  7.1. Were primary and secondary endpoints described and relevant to the question? Yes
  7.1. Were primary and secondary endpoints described and relevant to the question? Yes
  7.2. Were nutrition measures appropriate to question and outcomes of concern? Yes
  7.2. Were nutrition measures appropriate to question and outcomes of concern? Yes
  7.3. Was the period of follow-up long enough for important outcome(s) to occur? Yes
  7.3. Was the period of follow-up long enough for important outcome(s) to occur? Yes
  7.4. Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures? Yes
  7.4. Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures? Yes
  7.5. Was the measurement of effect at an appropriate level of precision? Yes
  7.5. Was the measurement of effect at an appropriate level of precision? Yes
  7.6. Were other factors accounted for (measured) that could affect outcomes? No
  7.6. Were other factors accounted for (measured) that could affect outcomes? No
  7.7. Were the measurements conducted consistently across groups? Yes
  7.7. Were the measurements conducted consistently across groups? Yes
  8. Was the statistical analysis appropriate for the study design and type of outcome indicators? Yes
8. Was the statistical analysis appropriate for the study design and type of outcome indicators? Yes
  8.1. Were statistical analyses adequately described and the results reported appropriately? Yes
  8.1. Were statistical analyses adequately described and the results reported appropriately? Yes
  8.2. Were correct statistical tests used and assumptions of test not violated? Yes
  8.2. Were correct statistical tests used and assumptions of test not violated? Yes
  8.3. Were statistics reported with levels of significance and/or confidence intervals? Yes
  8.3. Were statistics reported with levels of significance and/or confidence intervals? Yes
  8.4. Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)? No
  8.4. Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)? No
  8.5. Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? No
  8.5. Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? No
  8.6. Was clinical significance as well as statistical significance reported? Yes
  8.6. Was clinical significance as well as statistical significance reported? Yes
  8.7. If negative findings, was a power calculation reported to address type 2 error? No
  8.7. If negative findings, was a power calculation reported to address type 2 error? No
  9. Are conclusions supported by results with biases and limitations taken into consideration? Yes
9. Are conclusions supported by results with biases and limitations taken into consideration? Yes
  9.1. Is there a discussion of findings? Yes
  9.1. Is there a discussion of findings? Yes
  9.2. Are biases and study limitations identified and discussed? Yes
  9.2. Are biases and study limitations identified and discussed? Yes
  10. Is bias due to study's funding or sponsorship unlikely? Yes
10. Is bias due to study's funding or sponsorship unlikely? Yes
  10.1. Were sources of funding and investigators' affiliations described? Yes
  10.1. Were sources of funding and investigators' affiliations described? Yes
  10.2. Was the study free from apparent conflict of interest? Yes
  10.2. Was the study free from apparent conflict of interest? Yes