EAL

FL: Fluoride and the Brain (2010)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To study the effect of fluoride in drinking water on children's intelligence.

Inclusion Criteria:

Children
Ages eight to 13 years
Jiangsu Province.

Exclusion Criteria:

Children who had been absent from either village for two years or longer or who had a history of brain disease or head injury.

Description of Study Protocol:

Recruitment

In Wamiao, 93% of the children (222 out of 238) were included for the study, while in Xinhuai, 95% were included (290 out of 305)
The children in Wamiao were divided into five subgroups according to the level of fluoride in their drinking water:
- Group A: Less than 1.0mg per L
- Group B: 1.0 to 1.9mg per L
- Group C: 2.0 to 2.9mg per L
- Group D: 3.0 to 3.9mg per L
- Group E: More than 3.9mg per L
Group F consisted of all subjects from Xinhuai (0.18 to 0.76mg per L of fluoride in the drinking water).

Design

Cross-sectional study.

Blinding Used

An IQ assessment was administered to the children in a school class, under the supervision of an independent examiner and two assistants and according to the directions of the CRT-RC manual for the test administration conditions. A double blind system was used.

Statistical Analysis

Data were analyzed using SAS and Benchmark Concentration software (BMCS).

Mean±SD
Distribution analysis
Pearson correlation coefficient.

Data Collection Summary:

Timing of Measurements

The study was conducted between September and December 2002.

Dependent Variables

IQ and rate of retardation
Urine fluoride levels
Urine fluoride-to-creatinine ratio
Urinary iodine
Urinary iodine-to-creatinine.

Independent Variables

Drinking water fluoride levels.

Control Variables

Age
Parents' education
Gender.

Description of Actual Data Sample:

Initial N: 512 children
Age: Eight to 13 years
Ethnicity: Chinese
Other relevant demographics: Gender, parents' education, family income
Location: Living in two villages in Sihong County, Jiangsu Province, China.

Summary of Results:

The results indicate that significant differences were present between the villages in the levels of fluoride in the drinking water and urine, but not in the urinary iodine levels.

In the high-fluoride village of Wamiao (water fluoride: 2.47±0.79mg per L; range: 0.57 to 4.50mg per L), the mean IQ of 222 children was significantly lower (92.02±13.00; range: 54 to 126) than in the low-fluoride village of Xinhuai (water fluoride: 0.36±0.15mg per L; range: 0.18 to 0.76mg per L), where the mean IQ of 290 children was higher (100.41±13.21; range: 60 to 128)
In the two villages there were significant differences between male, female and total children’s IQ. A significant difference was present between male and female children’s IQ in Wamiao but not in Xinhuai
In Xinhuai, 27.59% of the children tested in the range of bright normal (110 to 119) or higher, whereas only 8.11% did so in Wamiao. Moreover, 15.31% of the children in Wamiao were borderline intelligence IQ (70 to 79) or lower, but only 6.20% were in these classifications in Xinhuai
The children’s IQs were not related to urinary iodine, family income or parent’s education level. Higher drinking water fluoride levels were significantly associated with higher rates of mental retardation (IQ less than 70) and borderline intelligence (IQ 70 to 79).
The concentration-response relationship between the level of fluoride in the drinking water and an IQ score less than 80 (borderline intelligence and mental retardation) in the children is reported
A significant inverse correlation was found between IQ and the level of fluoride in urine, both when measured directly, as mg F per L, (Pearson correlation coefficient –0.174 , and when adjusted for creatinine, as mg F per mmol Cre, (Pearson correlation coefficient –0.164, P=0.005)
A further significant relationship was evident between the levels of fluoride in drinking water and in urine, both when the latter was measured directly, as mg F per L (Pearson correlation coefficient: 0.653, when adjusted for creatinine,as mg F per mmol Cre (Pearson correlation coefficient: 0.503, P<0.001)
The average IQ of the children in each age group in Xinhuai was higher than in Wamiao
Above age 10, the IQ had a tendency to decrease, but it did not do so significantly in either village. Correlation analysis showed that there was a significant relationship between IQ and age in Xinhuai (Pearson correlation coefficient: –0.216, P<0.01) but not in Wamiao (Pearson correlation coefficient: –0.083, P=0.218).
When combined, the data of the two villages indicated the existence of a significant relationship between age and IQ (Pearson correlation coefficient: –0.207, P<0.01).
Children’s IQ in each group by family income in Xinhuai was higher than that in Wamiao
No significant relationships were present between the children’s IQ and education level of parents, in both Wamiao and Xinhuai (Pearson correlation coefficient: –0.119 and 0.113, respectively, P>0.05)
At each parent’s education level, the children’s IQ in Xinhuai was higher than in Wamiao
The Benchmark Concentration (BMC) for the concentration-response relationship between IQ less than 80 and the drinking water fluoride level was 2.32mg per L, and the lower-bound confidence limit (BMCL) of the BMC was 1.85mg per L.
Taking dental fluorosis and other sources of dietary fluoride into account, the reference value concentration (RfC) for fluoride was calculated to be 0.925mg per L, which is very close to the current national Chinese standard of less than 1.0mg per L.

Fluoride in Drinking Water, Urine and Urinary Fluoride to Creatinine Ratios in Wamiao and Xinhuai

	Village	No. Samples	Mean±SD	Range	P
Fluoride in drinking water (mg per L)	Wamiao	222	2.47±0.79	0.57–4.50	<0.001
Fluoride in drinking water (mg per L)	Xinhuai	290	0.36±0.15	0.18?–0.76	<0.001
Urinary fluoride	Wamiao	155	3.47±1.95	0.90–12.50	<0.001
Urinary fluoride	Xinhuai	135	1.11±0.39	0.37–2.50	<0.001
Urinary fluoride to creatinine	Wamiao	155	0.82±0.75	0.13–4.69	<0.001
Urinary fluoride to creatinine	Xinhuai	135	0.24±0.10	0.09–0.71	<0.001

Children’s IQ in Wamiao and Xinhuai

Village	Male		Female		Total		Range
Village	N	Mean ±SD	N	Mean ±SD	N	Mean ±SD	Range
Wamiao	122	94.73±13.09	100	88.72±12.16^*	222	92.02±13.00	54-126
Xinhuai	159	100.69±13.52^#	131	100.08±12.87^†	290	100.41±13.21^†	60-128

*P<0.01 compared with male data. ^†P<0.01 compared with Wamiao.

Level of Fluoride in Drinking Water and Children’s IQs

Village	F in Drinking Water (mg per L)			IQ and Rate of Retardation
	Group	No. Samples	Water F Level (Mean±SD)	No. Children	IQ (Mean±SD)	Rate of IQ < 80 (%)
Xinhuai	F	290	0.36±0.15	290	100.41±13.21	6.55
Wamiao	A	9	0.75±0.14	9	99.56±14.13	0.00
	B	42	1.53±0.27	42	95.21±12.22*	9.52
	C	111	2.46±0.30	111	92.19±12.98†	14.41*
	D	52	3.28±0.25	52	89.88±11.98†	21.15†
	E	8	4.16±0.22	8	78.38±12.68†	37.50†

*P<0.05. ^†P<0.01 compared with group F.

Author Conclusion:

This study found a significant inverse concentration-response relationship between the fluoride level in drinking water and the IQ of children. As the fluoride level in drinking water increased, the IQ fell and the rates of mental retardation and borderline intelligence increased.
Urinary iodine levels do not appear to affect the differences in IQ in children between the two villages
The Benchmark Concentration (BMC) of 2.32mg F per L and the lower-bound confidence limit of the BMC (BMCL) of 1.85mg F per L were calculated from the concentration-response relationship between the rates of mental retardation (IQ less than 70) and borderline intelligence (IQ 70 to 79) and the level of fluoride in the drinking water. In endemic fluorosis areas, drinking water fluoride levels greater than 1.0mg per L may adversely affect the development of children's intelligence.

Funding Source:

University/Hospital:

School of Public Health, Fudan University (Formerly Shanghai Medical University), Shanghai, China

Reviewer Comments:

The study results are very interesting. There are other etiologic factors that may influence the results.
Further demographic details of the population are required. It would also be interesting to know its effects on growth and development indicators.
The researchers are not blinded and the sample is not randomized. There is no representative sample for comparison.
Additional controlled population trials are required.

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
	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
	4.	Is the intervention or procedure feasible? (NA for some epidemiological studies)	N/A

Validity Questions
1.	Was the research question clearly stated?		Yes
	1.1.	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
	1.3.	Were the target population and setting specified?	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
	2.2.	Were criteria applied equally to all study groups?	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?	No
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
	3.2.	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
	3.4.	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
	3.6.	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
	4.1.	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%.)	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
	4.5.	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?		Yes
	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.)	Yes
	5.3.	In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?	Yes
	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
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
	6.2.	In observational study, were interventions, study settings, and clinicians/provider described?	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?	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
	6.7.	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
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
	7.2.	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?	N/A
	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
	7.6.	Were other factors accounted for (measured) that could affect outcomes?	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
	8.1.	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
	8.3.	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)?	N/A
	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
	8.7.	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
	9.1.	Is there a discussion of findings?	Yes
	9.2.	Are biases and study limitations identified and discussed?	Yes
10.	Is bias due to study's funding or sponsorship unlikely?		Yes
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.2.	Was the study free from apparent conflict of interest?	Yes