Childhood Exposure to Ambient Air Pollution and Obesity: Comparison

Please note this is a comparison between Version 2 by Chao Huang and Version 4 by Amina Yu.

Obesity has become a worldwide epidemic; 340 million of children and adolescents were overweight or obese in 2016, and this number continues to grow at a rapid rate. Epidemiological research has suggested that air pollution affects childhood obesity and weight status, but the current evidence remains inconsistent. Therefore, the aim of this meta-analysis was to estimate the effects of childhood exposure to air pollutants on weight. Our research found that air pollution can be regarded as a probable risk factor for the weight gain of children and adolescents. The next step is to conduct longer-term and large-scale studies on different population subgroups, exposure concentrations, and pollutant combinations to provide detailed evidence. Meanwhile, integrated management of air pollution is essential.

childhood
air pollution
obesity
BMI

1. Introduction

Obesity has become a worldwide epidemic and urgent health issue ^[1]. The prevalence of overweight and obesity has increased considerably in the last few decades and nearly tripled since 1975. With regard to children and adolescents, 340 million of them were overweight or obese in 2016, and this number continues to grow at a rapid rate ^[2][3]. Childhood obesity has been associated with obesity and increased risks for chronic disease in adulthood ^[4][5], and these adverse effects may last the whole lifetime ^[6]. Research has identified multiple factors that can lead to childhood obesity and it has been shown that childhood obesity can be attributed to genetic, dietary, and behavioral factors ^[7]. Despite genetic and metabolic predispositions, the rising epidemic of obesity indicates environmental factors may play a role in accelerating the progression of childhood obesity ^[8].

The Global Burden of Disease study revealed that air pollution can be the most adverse environmental health hazard for disease and mortality worldwide ^[9][10]. Well over 80% of urban dwellers suffer from air pollution, and the most seriously affected individuals were low-income residents ^[11]. In recent years, mounting evidence suggests that air pollution can be an obesogenic factor ^[12]. It is mainly through the biochemical and behavioral pathways that air pollution affects body weight. Metabolic disorders ^[13], inflammatory reactions ^[14], reduced sleep duration and quality ^[15] that are caused by air pollution all contribute to the accumulation of adipose tissue and weight gain, as has been demonstrated in animal trials. Additionally, the decline in air quality reduces a person’s willingness to engage in outdoor activities ^[16], which in turn increases indoor time, in order to reduce the impact of pollution on the human body ^[17].

Although there are numerous focus on air pollution and obesity, the effects remained inconsistent and differed among the populations, pollutant types, and pollutant concentrations ^[12]. It was found that previous ones were more concentrated on exposure during pregnancy ^[18][19], whereas recent one have increasingly examined the direct effects of children’s exposure to air pollution on obesity ^[20][21]. However, the findings seem to be inconsistent even in children and adolescents only ^[22][23][24]. For instance, Fioravanti et al. suggested that the evidence that air pollution causes obesity was limited ^[23]. In contrast, some indicated that long-term exposure to air pollutants might be correlated with weight gain and the development of obesity ^{[20][21][25][26]}. Among the available information, the existing ones have been mostly concentrated on adults or whole populations, and quantitative synthesis of the contribution of air pollution to children and adolescents remains scarce ^[12][27][28]. A meta-analysis by Parasin et al. examined the relationship between air pollution and childhood obesity, but did not distinguish between exposure during pregnancy and individual exposure, and also did not standardize when combining the effects of pollutants across these ^[29]. Therefore, it was believe that the topic still has potential for further research. As such, it was to systematically and quantitatively analyze the scientific evidence on the influence of exposure to air pollution on weight gain and obesity in childhood.

2. The Association between Childhood Exposure to Ambient Air Pollution and Obesity

It was s

1. Introduction

Obesity has become a worldwide epidemic and urgent health issue [1]. The prevalence of overweight and obesity has increased considerably in the last few decades and nearly tripled since 1975. With regard to children and adolescents, 340 million of them were overweight or obese in 2016, and this number continues to grow at a rapid rate [2,3]. Childhood obesity has been associated with obesity and increased risks for chronic disease in adulthood [4,5], and these adverse effects may last the whole lifetime [6]. Research has identified multiple factors that can lead to childhood obesity and it has been shown that childhood obesity can be attributed to genetic, dietary, and behavioral factors [7]. Despite genetic and metabolic predispositions, the rising epidemic of obesity indicates environmental factors may play a role in accelerating the progression of childhood obesity [8].

The Global Burden of Disease study revealed that air pollution can be the most adverse environmental health hazard for disease and mortality worldwide [9,10]. Well over 80% of urban dwellers suffer from air pollution, and the most seriously affected individuals were low-income residents [11]. In recent years, mounting evidence suggests that air pollution can be an obesogenic factor [12]. It is mainly through the biochemical and behavioral pathways that air pollution affects body weight. Metabolic disorders [13], inflammatory reactions [14], reduced sleep duration and quality [15] that are caused by air pollution all contribute to the accumulation of adipose tissue and weight gain, as has been demonstrated in animal trials. Additionally, the decline in air quality reduces a person’s willingness to engage in outdoor activities [16], which in turn increases indoor time, in order to reduce the impact of pollution on the human body [17].

Although there are numerous original studies on air pollution and obesity, the effects remained inconsistent and differed among the populations, pollutant types, and pollutant concentrations [12]. We found that previous studies were more concentrated on exposure during pregnancy [18,19], whereas recent studies have increasingly examined the direct effects of children’s exposure to air pollution on obesity [20,21]. However, the findings seem to be inconsistent even in studies of children and adolescents only [22,23,24]. For instance, Fioravanti et al. suggested that the evidence that air pollution causes obesity was limited [23]. In contrast, some studies indicated that long-term exposure to air pollutants might be correlated with weight gain and the development of obesity [20,21,25,26]. Among the available review articles, the existing studies have been mostly concentrated on adults or whole populations, and quantitative synthesis of the contribution of air pollution to children and adolescents remains scarce [12,27,28]. A meta-analysis by Parasin et al. examined the relationship between air pollution and childhood obesity, but did not distinguish between exposure during pregnancy and individual exposure, and also did not standardize when combining the effects of pollutants across studies [29]. Therefore, we believe that the topic still has potential for further research. As such, that this study aimed to systematically review and quantitatively analyze the scientific evidence on the influence of exposure to air pollution on weight gain and obesity in childhood.

2. The Association between Childhood Exposure to Ambient Air Pollution and Obesity

It was showed that long-term exposure to particulate matter and NO₂ was significantly correlated with the risk of childhood obesity, while BMI also showed similar elevated results. Although O₃ and NO_x also had a positive effect on the increase in weight status, none reached significant levels. Notably, as the aerodynamic diameter of particulate matter decreases, the fattening effect on children increases, and researchers have begun to concentrate on the smaller particle size pollutants (PM₁). Of the 15 studies that were included in the analysis, around 73% were published in the last three years, and most were conducted in developing countries. We compared a meta-analysis of the association between air pollutants and obesity in adults [28], where half of the included studies were published after 2019, with the difference that the study areas were predominantly developed countries. An identifiable trend is that concerns about air pollution and childhood obesity are rising rapidly in developing countries. One plausible explanation is that although developed countries still maintain high rates of childhood obesity [49,50], the effect of air pollutants on body weight has been limited because air pollution levels have declined significantly in these countries [28]. Developing countries, in contrast, appear confronted with a double crisis, with increasing prevalence and growth rates of childhood obesity on the one hand [51], and deteriorating air quality resulting from urbanization and industrialization on the other [52,53]. Thus, numerous original studies were conducted in developing countries in recent years, and the effects tend to be more significant, further providing foundations for the analysis of our research. As the main air pollutants of concern in the present study, particulate matter significantly influenced childhood obesity and BMI growth. Our findings were consistent with the previous hypothesis that with smaller aerodynamic diameters of respirable particulate matter, the more toxic compounds would be adsorbed and also more easily inhaled deep into the lungs, therefore are more harmful to health [54,55]. In contrast to children, long-term exposure to PM₁₀ and PM_2.5 showed insignificant effects on adult obesity according to a meta-analysis that was conducted on adults [28]. Similar results were found for NO₂ and O₃, both pollutants were positively associated with the development of obesity. As can be seen, the effects of different pollutants on people can be diverse and complex, even for the same pollutant, the impact can vary depending on the characteristics of the population (i.e., age, gender, region). These specific mechanisms require further investigation and validation. While the mechanisms linking exposure to air pollution and obesity are not completely understood, biochemical mechanisms have been commonly mentioned and accepted as the main obesity-causing mechanisms in relation to air pollutants [12,25,56]. Firstly, from the perspective of human metabolism, air pollutants entering the body from the respiratory tract may increase oxidative stress in tissues and systems [57]. Take PM2.5, as an example, it can affect gene expression in mitochondria in brown adipose tissue, resulting in increased production of reactive oxygen species in brown fat stores, which lead to metabolic dysfunction [13], and susceptibility to lipid metabolism and glucose metabolism [58]. Secondly, the inflammatory response that is triggered by air pollutants can lead to vascular damage as well as insulin resistance, can also have an impact on body weight [14]. Studies also found that the occurrence of sleep-disordered breathing (SDB) was related to exposure to air pollutants [59]. Those who lived in regions with high NO2 and PM2.5 levels were much more likely to suffer from SDB, which in turn caused mental and physical health

disparities [60]. Sleep deprivation correlated with decreased levels of leptin secretion, lower thyroid stimulating hormone secretion, and lower glucose tolerance, all of which may increase BMI status[15]. Finally, behavioral mechanisms can be explained in another direction [12]. For example, air pollution can reduce people’s willingness to participate in outdoor activities [16]. In addition, it can also improve the consumption of trans fats and fast food [61], which may contribute to obesity. However, attention should be drawn to the fact that while the obesogenic mechanisms of air pollution have been validated in animal models, uncertainties remain for humans or for different pollutants, and more research should be conducted to elucidate such pathways. The strength of the present study is that it comprehensively and quantitatively assesses the relationship between long-term exposure to air pollutants and childhood obesity. Previous studies focused on the whole population [12]or adults [28], with limited studies on children and adolescents [25,62]. Meanwhile, the majority of the original studies that were included in this study were published in the past three years, and the results are relatively new. Thirdly, the exposure doses in the original studies were mostly different, thus it is difficult to compare the effects, and we converted the data in a standardized way to improve the comparability of the data. Finally, analyses and collations were performed according to the standard methods that are required by the PRISMA checklist. However, this meta-analysis still has many limitations that need to be noted. Firstly, although we systematically searched the currently that is available epidemiological evidence, the amount of research was still limited and the potential sources of heterogeneity remain to be explored. When we integrated the results across studies, the quality of the articles varied, exposure was not measured and estimated in a standardized way, analytical methods were imperfect, and the certainty of the evidence in the articles was generally poor, so caution should be exercised in interpreting the results as well. Secondly, the findings were based on numerous cross-sectional studies; therefore, causality was difficult to be determined accurately. According to GRADE system, the level of evidence for observational studies was still low. Thirdly, due to the complexity of growth patterns, the BMI that was applied to measure obesity in adults may not be applicable to a certain extent to children and adolescents. Fourth, for younger children (before two years of age), early obesity may be associated with the subsequent catch-up growth of low birth weight due to maternal

exposure to air pollution [63], and the mechanisms for infants need to be further probed. Finally, obesity is a disease with complex causes, the magnitude of the direct role that is contributed by air pollution was unclear, and residual bias (i.e., socio-economic conditions, physical activity) may still influence the outcomes. For example, high-income families (or parents with higher education levels) tend to live in more privileged residential areas with relatively lower levels of air pollution, better green spaces and have a more structured diet, while low-income families tend to be the opposite. Likewise, parents who live in more polluted areas may restrict their children's outdoor activities to reduce the exposure to air pollutants. These potentially confounding variables were not comprehensively captured and reasonably explained in studies

Thowed that long-term exposure to particulate matter and NO2 was significantly correlated with the risk of childhood obesity, while BMI also showed similar elevated results. Although O3 and NOx also had a positive effect on the increase in weight status, none reached significant levels. Notably, as the aerodynamic diameter of particulate matter decreases, the fattening effect on children increases, and researchers have begun to concentrate on the smaller particle size pollutants (PM1).

Of the 15 that were included in, around 73% were published in the last three years, and most were conducted in developing countries. It was compared a meta-analysis of the association between air pollutants and obesity in adults ^[28], where half of the included were published after 2019, with the difference that the areas were predominantly developed countries. An identifiable trend is that concerns about air pollution and childhood obesity are rising rapidly in developing countries. One plausible explanation is that although developed countries still maintain high rates of childhood obesity ^[30][31], the effect of air pollutants on body weight has been limited because air pollution levels have declined significantly in these countries ^[28]. Developing countries, in contrast, appear confronted with a double crisis, with increasing prevalence and growth rates of childhood obesity on the one hand ^[32], and deteriorating air quality resulting from urbanization and industrialization on the other ^[33][34]. Thus, numerous original ones were conducted in developing countries in recent years, and the effects tend to be more significant, further providing as the foundations.

As the main air pollutants of concern, particulate matter significantly influenced childhood obesity and BMI growth. The findings were consistent with the previous hypothesis that with smaller aerodynamic diameters of respirable particulate matter, the more toxic compounds would be adsorbed and also more easily inhaled deep into the lungs, therefore are more harmful to health ^[35][36]. In contrast to children, long-term exposure to PM10 and PM2.5 showed insignificant effects on adult obesity according to a meta-analysis that was conducted on adults ^[28]. Similar results were found for NO2 and O3, both pollutants were positively associated with the development of obesity. As can be seen, the effects of different pollutants on people can be diverse and complex, even for the same pollutant, the impact can vary depending on the characteristics of the population (for example, age, gender, region). These specific mechanisms require further investigation and validation.

While the mechanisms linking exposure to air pollution and obesity are not completely understood, biochemical mechanisms have been commonly mentioned and accepted as the main obesity-causing mechanisms in relation to air pollutants ^[12][25][37]. Firstly, from the perspective of human metabolism, air pollutants entering the body from the respiratory tract may increase oxidative stress in tissues and systems ^[38]. Take PM2.5, as an example, it can affect gene expression in mitochondria in brown adipose tissue, resulting in increased production of reactive oxygen species in brown fat stores, which lead to metabolic dysfunction ^[13], and susceptibility to lipid metabolism and glucose metabolism ^[39]. Secondly, the inflammatory response that is triggered by air pollutants can lead to vascular damage as well as insulin resistance, can also have an impact on body weight ^[14]. It was also found that the occurrence of sleep-disordered breathing (SDB) was related to exposure to air pollutants ^[40]. Those who lived in regions with high NO2 and PM2.5 levels were much more likely to suffer from SDB, which in turn caused mental and physical health disparities ^[41]. Sleep deprivation correlated with decreased levels of leptin secretion, lower thyroid stimulating hormone secretion, and lower glucose tolerance, all of which may increase BMI status^[15]. Finally, behavioral mechanisms can be explained in another direction ^[12]. For example, air pollution can reduce people’s willingness to participate in outdoor activities ^[16]. In addition, it can also improve the consumption of trans fats and fast food ^[42], which may contribute to obesity. However, attention should be drawn to the fact that while the obesogenic mechanisms of air pollution have been validated in animal models, uncertainties remain for humans or for different pollutants, and more research should be conducted to elucidate such pathways.

The strength is that it comprehensively and quantitatively assesses the relationship between long-term exposure to air pollutants and childhood obesity. Previous ones focused on the whole population ^[12]or adults ^[28], with limited on children and adolescents ^[43][44]. Meanwhile, the majority of the original ones that were included were published in the past three years, and the results are relatively new. Thirdly, the exposure doses in the original ones were mostly different, thus it is difficult to compare the effects, and it was converted the data in a standardized way to improve the comparability of the data. Finally, analyses and collations were performed according to the standard methods that are required by the PRISMA checklist.

However, there are many limitations that need to be noted. Firstly, although it was systematically searched the currently that is available epidemiological evidence, the amount was still limited and the potential sources of heterogeneity remain to be explored. When it was integrated the results across ones, the quality of the articles varied, exposure was not measured and estimated in a standardized way, analytical methods were imperfect, and the certainty of the evidence in the articles was generally poor, so caution should be exercised in interpreting the results as well. Secondly, the findings were based on numerous cross-sectional ones; therefore, causality was difficult to be determined accurately. According to GRADE system, the level of evidence for observational studies was still low. Thirdly, due to the complexity of growth patterns, the BMI that was applied to measure obesity in adults may not be applicable to a certain extent to children and adolescents. Fourth, for younger children (before two years of age), early obesity may be associated with the subsequent catch-up growth of low birth weight due to maternal exposure to air pollution ^[45], and the mechanisms for infants need to be further probed. Finally, obesity is a disease with complex causes, the magnitude of the direct role that is contributed by air pollution was unclear, and residual bias (for example, socio-economic conditions, physical activity) may still influence the outcomes. For example, high-income families (or parents with higher education levels) tend to live in more privileged residential areas with relatively lower levels of air pollution, better green spaces and have a more structured diet, while low-income families tend to be the opposite. Likewise, parents who live in more polluted areas may restrict their children's outdoor activities to reduce the exposure to air pollutants. These potentially confounding variables were not comprehensively captured and reasonably explained in studies

It was furt results of the study further reveal ther revealed the risk of air pollution on childhood obesity. The implications of air pollutants are direct and significant, not only for human health but also for the climate. Therefore, policy-makers can also benefit from these findings that economic development and urbanization can create a number of problems, especially in developing countries, and require reflection on how to develop appropriate policies to balance economic development and environmental pollution. A synergistic approach to air pollution and climate change management that is based on global cooperation is essential. Important sectors such as transportation, energy, and manufacturing are the main focus of high emissions of PM, SO2, NOx, and GHG. It is imperative to accelerate the transformation of the energy mix and use technology to drive low-carbon production. At the same time, it is essential to establish an integrated system of atmospheric monitoring, emissions supervision, and pollution remediation.

The present reviewas also provides insights for future studies. Firstly, long-term cohort onstudies with large samples of children and adolescents across age, gender, and ethnicity are required in order to provide more representative and convincing results. Secondly, the diagnosis of childhood obesity requires more diverse anthropometric measures such as waist circumference, waist-to-hip ratio, subcutaneous fat, and total and high-density

lipoprotein cholesterol. In addition, the health effects of ultrafine particulate matter still need to be clarified. Finally, interactions between multiple pollutants and their effects on humans also require estimation.