Journal of Public Health Advance Access published online on October 23, 2008
Journal of Public Health, doi:10.1093/pubmed/fdn097
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Effects of drinking water with high iodine concentration on the intelligence of children in Tianjin, China
Hong-Liang Liu, Director of Environmental Health1
Lawrence T. Lam, Senior Lecturer2
Qiang Zeng, Research Scientist1
Shu-qing Han, Research Scientist1
Gang Fu, Research Scientist1
Chang-chun Hou, Research Scientist1
1 Tianjin Centers for Disease Control and Prevention, 76 Hualong Road, HeDong District, Tiahjin 300011, People's Republic of China
2 Discipline of Paediatrics and Child Health, Faculty of Medicine, University of Sydney, Australia
Address correspondence to Lawrence T. Lam, Royal Alexandra Hospital for Children, Locked Bag 4001, Westmead, NSW 2145, Australia. E-mail: Lawrence.lam{at}usyd.edu.au or Hong-Liang Liu, Email: hongliang.liu{at}sina.com
Objective This study aimed to investigate the effects of drinking water with high concentrations of iodine on the intelligence of children in Tianjin, China.
Methods It was a population-based health survey utilizing a random cluster sampling design conducted in June 2005. Participants were recruited from the total population of primary school children attending years 1–4 with ages ranging from 8 to 10 years. Intelligence quotient (IQ) was assessed using the combined Raven's test, second edition. Linear regression analyses were applied to test for any association between water iodine concentration and IQ.
Results A total of 1229 students were recruited with a mean IQ of 105.8 (95% CI: 104.2–107.3). Water analyses indicated iodine concentrations were high in one rural region and exceedingly high in another with median values of 137.5 and 234.7 µg/l, respectively. There was a significant association between residing in the very high water iodine region and a reduction of IQ by an average of about nine points (P = 0.022), after adjusting for the potential confounding factors.
Conclusion Exposure to high iodine concentrations in drinking water has detrimental effects on the intelligence of children.
Keywords: epidemiology, health protection, public health
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Introduction |
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Iodine deficiency has long been identified to be clinically associated with endemic goitre and endemic cretinism among young children.1,2 It has also been recognized as a global public health problem and a threat to child health, especially in developing countries.3 The latest estimates, based on data collected by the WHO Global Database on Iodine Deficiency, suggested that there were about 2 billion people worldwide still not acquiring sufficient iodine intake in 2004.4
While endemic cretinism is the most severe manifestation of the effects of iodine deficiency on brain development, more concerning are the impairing effects on cognitive development, intellectual abilities and school performance of children.5,6 These may have long-term social and economic consequences for communities where iodine deficiency is prevalent.
In terms of the effect of iodine deficiency on intellectual development, there has been a growing wealth of literature from different parts of the world including both developed and developing countries.7–13 The detrimental effects of iodine deficiency on intellectual development, particularly in terms of the intelligence quotient (IQ) as a common assessment of intelligence, in children have been demonstrated in all studies. For example, in a meta-analysis of 37 studies conducted in China with a total of 12 291 children, the IQ of those living in naturally iodine-sufficient areas was compared with those in severely deficient areas. It was found that children living in iodine-sufficient areas scored a higher IQ of more than 12 points than those in severely deficient areas without iodine supplement.11 When compared with children who resided in iodine-deficient areas with inadequate supplementation and also who had received iodine during their mothers' pregnancy and after birth, children living in the iodine-sufficient areas had higher IQ of 
12 and 5 points, respectively.11 This phenomena also occurred in developed countries with less severe deprivation of iodine intake. Another study in Spain examined the effects of mildly insufficient iodine intake, according to the WHO criteria,14 on the intelligence of children.8 It was found that the IQ was significantly higher in school children with median urinary iodine levels (UI) above 100 µg/l when compared with those with a UI of 90 µg/l.
Primary intervention of universal salt iodization and dietary supplements have been suggested.15 Intervention programmes have also been implemented in many developing countries including China.16 Although there have been recorded success in addressing the problems relating to iodine deficiency, on the other end of the spectrum concerns have been raised. There has been a growing awareness of the effects of excessive iodine intake on child health. Particularly, it has been recognized that excessive iodine intake is also the cause of endemic goitre and associated with large thyroid volumes in children.17–19 It has been suggested that the association between high iodine intake and large thyroid volume may due to an autoimmune process of lymphoid infiltration of the thyroid resulting in an inhibition of thyroid hormone release and triggering a process similar to iodine deficiency.17–19
Since iodine deficiency is an aetiological factor for endemic goitre and lower IQ in children, and excessive iodine intake is also an aetiological factor for endemic goitre, it would be logical to deduce that excessive iodine intake could also have a detrimental effect on IQ in children. It may also be possible that a similar mechanism of iodine deficiency on lower IQ can be applied to excess iodine and lower IQ. So far, no studies have been found in the literature on this topic. Hence, the aim of this study is to investigate the effect of drinking water with high iodine concentration on the IQ of children. It is hypothesized that children with excessive iodine intake will have a lower IQ than those who receive a sufficient level of iodine.
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Methods |
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This was a population-based health survey with a randomized cluster sampling design. The sample frame included all primary schools with children aged between 8 and 10 years in the metropolitan and rural regions of the Tianjin city, China. The sample frame for water sampling also covered the same areas as the school samples. This presented a population size of 9 178 500 children aged between 8 and 10 years. The study was conducted in June 2005 as part of the on-going National surveillance of Iodine Deficiency Prevention Programme in China. Institute ethics approval was granted by the Ethics Committee of the Tianjin Centres for Disease Control and Prevention, China.
Water samples were randomly collected from 18 separate administrative areas, including the metropolitan city of Tianjin and three major outskirt rural regions, utilizing a population proportion sampling technique. Drinking water samples were mainly collected from taps within metropolitan areas and wells or springs in the rural regions. The recruitment of primary students consisted of a two-stage process with stratification according to the population size of children within the target age range in each of the 18 administrative areas. First, using individual schools as the primary sampling unit, a number of schools were randomly selected with a probability which is proportional to the size of the target population in each area. Second, using the class as the secondary sampling unit, different clusters of students were randomly selected from each of the selected schools.
The exposure variable of the study was defined as iodine intake through drinking water. It was measured from the water samples collected within the areas or regions in which the recruited children resided. Chemical analyses for iodine concentration were then conducted on these samples using the arsenic–cerium redox method, protocol of which has been detailed in a previous study by Lu et al.20
In terms of data collection on the outcome variable, namely intelligence, and other potential confounding variables, participating children were visited by trained researchers for the purpose of conducting a personal assessment as well as to collect samples for chemical analyses. The intelligence of children was assessed using the Combined Raven's Intelligence test (second edition) which is a validated and widely used assessment instrument for children and young adolescents.21 It has been recommended as the standard instrument for intelligence assessment by the China National Committee on Iodine Deficiency Disorder (IDD). In this study, the intelligence was quantified as the IQ which was calculated from the raw score of each child using the appropriate normative information. For those children residing in the metropolitan city, the national norm obtained from city children was used, in the same manner; the rural norm was used for those who resided in the rural regions.
Other information collected included sex, school year and age, which also documented the year of birth after the 1995 implementation of the national dietary iodine supplement programme. Included in this study were children born in the years of 1995–97, designating the first cohort of children receiving iodine supplement, the subsequent year and the year after. As these children also received dietary iodine from iodized salt, the salt iodine (SI) concentration was considered as a confounding factor that needed to be adjusted for. Participants were also asked to bring a sample of salt they used at home to be analysed for iodine concentration. These salt samples were then analysed using the iodometric titration method recommended by the International Council for the Control of Iodine Deficiency Disorders.22 It has been recommended by the WHO that median UI concentration be used as the epidemiological criteria for assessing iodine nutritional intake.4 However, due to technical difficulties of obtaining urinary samples from the whole study population, samples were collected on about one-third of the total sample. UI concentration was also analysed using the arsenic–cerium redox method. Results on the correlation between UI and water iodine concentration as well as the SI were strong and highly significant, as was reported in the study by Zhao et al.23
Data were analysed using the Stata statistical software program.24 Since the study was of a cluster sampling design, data were set up with the survey design function utilizing the svy commands for handling the cluster sampling effect. As the distribution of the calculated IQ was normal, it was treated as a continuous variable without any transformation. However, due to the highly skewed distribution of water iodine concentration and could not be normalized with transformations, the exposure variable was categorized into areas of non-high, high and very high water iodine concentration according to the proportion of samples with water iodine concentrations exceeding the recommended standard. The China National Committee on IDD recommended that geographic areas with a water iodine concentration <150 µg/l be considered as non-high, between 150 and 300 µg/l as high and >300 µg/l very high. Logarithm transformation was applied to the SI concentration due to its skewed distribution. Bivariate analyses were conducted to examine unadjusted relationships between all variables of interest and IQ. Linear regression modellings were applied to test for the association between drinking water iodine concentration and IQ after adjusting for potential confounding factors identified in the bivariate analyses. For the inclusion of any variables in the initial logistic regression model, the criterion of a bivariate association with a P-value of about 0.20 was used. All statistical tests of hypothesis were adjusted for the cluster sampling design.
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Results |
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A cluster random sample was obtained from 30 different schools and 58 different classes resulting in a total of 1229 students. The characteristics of these students were summarized in Table 1. The sample consisted of primary school children aged between 8 and 10 years with slightly more than one-third for the 10 years old group. There were slightly more females (52%) than males. In terms of school years, nearly one-third of the sample were in year 2, another one-third in year 3 and less than one-third in year 4 with the remaining being in year 1. The distribution of iodine concentration in salt samples was highly skewed with a mean value of 29.5 (95% CI: 28.8–30.1) mg/kg, ranging from 0.0 to 76.8 mg/kg with a median of 30.5 mg/kg. Similarly, the distribution of UI concentration was also skews with a mean value of 265.2 (95% CI: 246.4–284.1) µg/l, ranging from 23.8 to 1226.0 µg/l with a median of 228.0 µg/l. As expected, the correlation between the two concentrations were strong (r = 0.76) and highly significant (P < 0.001). Due to the fact that only one-third of the total sample had UI data and there was a strong correlation between UI and SI, UI was not included in further analyses.
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In terms of the outcome variable, the mean IQ of the sample was 105.8 (95% CI: 104.2–107.3) with a median of 106, and ranged from a minimum of 54 to a maximum of 146. A test for normality on the distribution of the IQ suggested no deviation from a normal pattern (P = 0.141).
The results on water iodine analyses by major geographical regions were summarized in Table 2. As shown there was a wide spectrum of different iodine concentrations in these drinking water samples, ranging from a minimum of 3.3 µg/l to a maximum of 527.7 µg/l. Even within each geographical region or area, various concentrations were also observed. According to the methods for defining areas or regions with various water iodine concentrations mentioned above, one outskirt rural region was classified as an area with very high water iodine, another as a high concentration area, with the remaining as non-high areas (Table 2).
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The bivariate relationships between the exposure variable, log SI, other variables and IQ were examined. The results were summarized in Table 3. As shown, the overall association between water iodine and IQ was insignificant (P = 0.108). However, there was a significant difference in the pair-wise comparison between very high areas and non-high areas (P = 0.035). In terms of other variables, significant association was also found between log SI and IQ only (P = 0.004). Both age or year of birth and school year attained a P-value of
0.2, thus these variables were included in the linear regression analyses.
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The results obtained from the linear regression modelling were presented in Table 4. There was a significant association between water iodine concentration and IQ, particularly for the region with very high water iodine levels (P = 0.020), after adjusting for log salt concentration, age and school year. The results indicated that for children who resided in regions with a very high water iodine concentration, there was on average a reduction of IQ by nearly nine points (b = –8.7, 95% CI: –15.9 to –1.4) in comparison with those who resided in a non-high water iodine area. When comparing children living in areas with a high water iodine concentration with those in the non-high areas, a slight reduction of IQ by about two points was observed, however, it was not significant. There was also a significant association between year of birth and IQ, which seemed to exhibit a dose–response relationship. There was a progressive increase in IQ by about four (P = 0.072) and eight (P = 0.015) points for children born in 1996 and 1997 when compared with those who were born in 1995, the year China first implemented the national dietary iodine supplement programme. No interaction effect between water and SI concentration on IQ was found.
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Discussion |
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Main findings of this study
This exploratory study aims to investigate the effect of drinking water with high iodine concentration on intelligence among children. To the knowledge of the authors, this is the first attempt that has explored the relationship between high iodine intake and IQ in China as well as other parts of the world. The results indicated that, after adjusting for potential confounding factors, drinking water with high iodine concentration is significantly associated with a reduction of IQ. Those children who have been exposed to very high water iodine concentrations, on average have a lower IQ by nearly nine points compared with those who live in areas with lower water iodine levels. As suggested by the results, it is a strong and statistically significant association. Unfortunately, no similar study has been identified that can provide results for comparison.
What is already known and possible explanation of the results
The results obtained indicate that high iodine intake is detrimental to the mental and cognitive development of children. They further suggest that exposure to high levels of iodine in water, on its own, is an independent risk factor of lower IQ. There could be many possible explanations for such findings. First, children are exposed to high iodine levels through a direct intake of water with high iodine concentrations throughout their life span. The accumulative exposure to a high concentration of iodine has a direct effect on all stages of cognitive development. Second, the exposure may not only be due to a direct intake of water with high levels of iodine. It may also come from an early exposure to high iodine levels during pregnancy. This may be more important than a high iodine intake later in life. There has been growing evidence to suggest that the effect of iodine deficiency on IQ is probably a side effect of thyroid dysfunction. As iodine deficiency is a direct cause of thyroid dysfunction, impairment of thyroid hormone synthesis may, directly or indirectly, interfere with brain maturation during the foetal or post-natal developmental stages. This may probably due to the regulation of the expression of target genes.25–28 On the other hand, as mentioned earlier, the association between high iodine intake and large thyroid volume may due to an autoimmune process of lymphoid infiltration of the thyroid resulting in an inhibition of thyroid hormone release and triggering a process similar to iodine deficieny. This may also be the underlying biological mechanism for the association between high iodine intake and low IQ.
What this study adds
There are some public health implications from the results obtained. The possibility of the detrimental effect of high iodine intake on the physical health as well as the mental and cognitive development in children has constituted two important issues. On the one hand is the need for an urgent response to the population who are at high risk of exposure. On the other hand is the overall policy of the implementation of the national dietary iodine supplement programme. As has been demonstrated, the effect of iodine deficiency on low IQ is reversible with a proper iodine supplement programme,11 it can be argued that the effect of high iodine intake can also be reversed. Children and parents who are at high risk of exposure should, and in this case can easily, be identified. With proper education and communication, the danger of high iodine intake should be highlighted. In areas with very high water iodine concentration, the population should be advised to take appropriate actions in cutting down other potential dietary iodine intake such as seafood and iodine-enriched milk. In areas with extremely high water iodine levels, alternative water sources, such as importing water from a low iodine area, should be considered. This may require some intervention from the local governmental authority. On the policy level, it would be prudent to fine tune the blanket implementation of the national dietary iodine supplement programme with more detailed analyses of the geographical distribution of water iodine levels. Dietary iodine supplement should be attenuated according to local water iodine levels. In areas where water iodine concentration is high, dietary iodine should be greatly reduced or even eliminated.
Strengths and limitations of the study
There are strengths and weaknesses in this study as in all studies. The strengths of the study include the following: first, field researchers were all trained in clinical skills and techniques; second, all contacts with students were conducted according to a standardized protocol; third, information and chemical samples were also collected and analysed following a standardized protocol. All these procedures assisted in reducing potential biases such as measurement bias. Furthermore, the study employed a random cluster sampling method for generating the target sample. This contributed to a reduction of potential selection bias as in the case of a convenient sampling method. Some limitations have also been identified. First, the exposure measure of iodine intake is a surrogate measure of the actual iodine intake, given that drinking water would be the main source of dietary intake in the study sample. Second, information on other potential confounding factors, such as some socio-economic variables, for example, family income, home environments and parental IQ, that may exert an influence on the IQ of children was not collected. This has posed a limitation to the analyses of data being that the association between exposure and outcome has been inadequately adjusted for the unknown confounding effect. This may affect the precision of the strength of association obtained, however, the direction of association should, by and large, remain the same. Finally, this is an ecological and exploratory study by nature, thus results obtained should be considered as indicative not confirmative. Studies of better design, such as a prospective cohort study, should be carried out to confirm the results obtained.
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This study was supported by grants obtained from the Tianjin Health Bureau Important Talent Fund, item No. 2006.
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