*3.3. Zinc and Iron Status and Children's Behavior*

Results from our analyses (Table 7) using the model of total behavior score regressed on combined low levels of zinc and iron, having low zinc and iron was significantly associated with higher total behavior problems (*p* = 0.022), whereas high mother's education and being female were associated with reduced total behavior score. The model of externalization score regressed on combined low zinc and iron showed that being female and high mother's education are also associated with significantly lower externalizing behavior scores. The model of internalizing score regressed on combined low zinc and iron showed living in the suburbs to be positively associated with internalizing problems.

#### **4. Discussion**

In this community sample of Chinese pre-school children (*N* = 1314), with micronutrient levels measured at ages 3–5 years and behavioral problems measured at mean age 5.6 years, we found an association between micronutrient deficiency and total behavior problems. Firstly, we found that low zinc concentration is positively correlated with total behavior problems. Secondly, we found that combined low blood levels of zinc and iron is positively correlated with total behavior problems. These effects remained significant after controlling for sociodemographic factors such as gender and mother's education. We did not find a significant association between low iron status and behavior problems.

The finding of the association of zinc deficiency with child behavior problems is consistent with previous findings [46,47]. Zinc is a component of enzymes that affect growth in infancy and childhood, sexual maturation, neuro-motor development, and immunity. Specifically, zinc acts as the integral enzymatic agent in metabolic processes of proteins, carbohydrates, and lipids [48] and is used as a neurotransmitter or neuromodulator in the central nervous system [49]. Mental function is improved by zinc's promotion of normal brain development and physiology [22,23]. A recent study reported a relationship between low zinc and greater levels of hyperactivity, anxiety, and conduct problems [50]. Indeed, animal and human models have suggested a relationship between low serum zinc and anxiety, fear-like behaviors, and depression—implicating the role of the dopaminergic and serotonergic systems [51,52].



†

'HILQHGDV]LQFȝJG/; \* Statistically significant at two-sided *p* < 0.05 level.

**Table 5.** The effect of Zinc on children's behavior problems (*N* = 1314). 



†

'HILQHGDVLURQȝJG/; \* Statistically significant at two-sided *p* < 0.05 level.





'HILQHGDV]LQFȝJG/DQGLURQȝJG/ \* Statistically significant at two-sided *p* < 0.05 level.

The association of combined zinc and iron with children's behavior has been reported previously in [53]. It has been postulated previously that zinc and iron are thought to interact with one another for absorption. When levels of both zinc and iron are low, a more severe pattern of nutritional compromise is suggested. In fact, our results showed that blood zinc was positively correlated with blood iron (*r* = 0.31, *p* = 0.000), consistent with other published reports [54,55]. As previously discussed, zinc and iron both play important enzymatic roles in the dopamine metabolism pathways [56–58], and it has been suggested that zinc and iron deficiencies together can lead to additive effects in dopaminergic system alterations [50]. Interestingly, Oner *et al.* [50] also reported that while combined low serum levels of zinc and iron are correlated with increased hyperactivity, as a single nutrient effect, only zinc deficiency, not iron deficiency, was related to conduct problems and anxiety. As concluded in the paper, Oner *et al.* [50] suggested that zinc and iron deficiencies might be associated with different types of behavior problems. However, it is also possible that the association of combine low zinc and iron with behavior problems is driven by the effect of low zinc alone.

While not the focus of this current paper, the sociodemographic control variables also had effects on our outcome constructs. It is worth noting that the children whose mothers had more than 12 years education exhibited decreased externalizing behavior problems in all of our analyses. As the mothers are postulated to be the primary caregiver of the child, this observation points to the fact that children of mothers who had more education tend to exhibit less behavior problems, possibly as the result of better parenting practices in addition to better nutritional habits as results of increased education concerning nutrition. Furthermore, being female is also associated with decreased externalizing behavior and total behavior problems; such that girls in our sample tended to have lower incidents of externalizing and total behavior problems than boys.

Additionally, living in the suburbs has consistently been shown to be significantly associated with increase in total behavior problems and, even more strongly, in internalizing behavior problems. This result might not be too surprising because there has been ample evidence in the literature supporting that children of economically affluent families tend to develop more internalizing behavior problems, such as anxiety, depression, and substance abuse [59,60]. Globally, an epidemiological study has found depression rates to be higher in developed countries than in others [61]. The results from our data support the literature in that the suburban residents in our sample have the highest parental occupation and parental education levels, above both the urban and rural groups. This finding is not surprising given the suburban preschool is in a "new development zone", where up-and-coming young parents, generally of a better educational and socio-economic background, are pursuing relatively better and higher-paid occupations. Furthermore, parents who are in the transitional stage of social and economic rise in their lives and careers are likely to have high expectation of their children. Additionally, the parents themselves live very high-pressured lives from their own occupational demands, leading to the possibility that they are more likely to suffer from internalizing problems themselves, such as anxiety and depression. Previous studies have shown that parental symptoms of depression have been associated with children's problem behavior in clinical and community samples [62,63]. We postulate that this finding could be the result of a more stressful suburban parental lifestyle due

to social and occupational stress, factors that may indirectly affect their children by not having enough time to interact with them or through a decreased emphasis on food choice, which can contribute to nutrition status. Nevertheless, future research could include stress and lifestyle factors and their effects on malnutrition.

Limitations of this study should not be overlooked. First, these findings do not establish a causal relationship between zinc, iron and behavioral disturbance. However, results from intervention trials should be considered to elucidate whether a causal relationship truly exists. The nature of the study design also required that behavior be assessed during the last year of preschool while blood micronutrient levels were assessed when the children were ages 3–5 years. Consequently, participants differed in the time between times of micronutrient and behavior assessment. Secondly, nutrition was only assessed at a single point in time, making it difficult to generalize findings and assess the role of sustained nutrition deficiency, or even nutrition deficiency during the prenatal period. As a result, we were unable to separate the effects of chronic versus acute nutrition, which may have different implications on behavior [64]. Thirdly, although we included some sociodemographic factors in our analyses, other factors, such as income, should be considered in future studies. In addition, potential confounders such as the effects of other nutrients (e.g., vitamin D), food intake, and physical activity level should also be considered. Fourthly, examination of an all-Chinese sample in this age range limits application to other cultures, as cultural, ethnic, social, and age factors impact child rearing behaviors, including nutrition and feeding. Finally, while this study only included the parent-report, it would be equally important to consider other informants. Currently, the children in our cohort are at school age, and future studies will include youth self-report of behavior to assess the relationship between micronutrient deficiencies and behavior problems.

### **5. Conclusions**

Few studies have specifically examined the role of zinc and iron status in relation to child behavior. This sample of Chinese preschoolers suggests that low blood zinc is correlated to increased total behavior problems and that, additionally, combined low blood zinc and iron levels are also linked to increased total behavior problems early in childhood. Implications may include more public awareness of the importance of micronutrients. While sociodemographic factors are not easily modifiable, it is possible to encourage parents, children, and baby/child care professionals to make healthy food choices, including foods rich in zinc and iron.

### **Acknowledgements**

This research is supported by the National Institute of Environment Health Sciences (NIEHS, R01-ES018858, 1K02-ES019878-01) US; Jintan City Government; Jintan Hospital, China.
