Journal List > Ann Pediatr Endocrinol Metab > v.26(3) > 1516085615

TOOLS
Heo and Kim: Ambient air pollution and endocrinologic disorders in childhood
Review Article

Ann Pediatr Endocrinol Metab 2021;26(3):158-170.

Published online: 30 September 2021

DOI: https://doi.org/10.6065/apem.2142132.066

Ambient air pollution and endocrinologic disorders in childhood

You Joung Heo, Hae Soon Kim

Department of Pediatrics, Ewha Women’s University College of Medicine, Seoul, Korea

Address for correspondence: Hae Soon Kim Department of Pediatrics, Ewha Women’s University College of Medicine, 260, Gonghang-daero, Gangseo-gu, Seoul 07804, Korea Email: hyesk@ewha.ac.kr

Received 22 June 2021       Revised 10 August 2021       Accepted 23 August 2021

© 2021 Annals of Pediatric Endocrinology & Metabolism

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Ambient air pollution has been proposed as an important environmental risk factor that increases global mortality and morbidity. Over the past decade, several human and animal studies have reported an association between exposure to air pollution and altered metabolic and endocrine systems in children. However, the results for these studies were mixed and inconclusive and did not demonstrate causality because different outcomes were observed due to different study designs, exposure periods, and methodologies for exposure measurements. Current proposed mechanisms include altered immune response, oxidative stress, neuroinflammation, inadequate placental development, and epigenetic modulation. In this review, we summarized the results of previous pediatric studies that reported effects of prenatal and postnatal air pollution exposure on childhood type 1 diabetes mellitus, obesity, insulin resistance, thyroid dysfunction, and timing of pubertal onset, along with underlying related mechanisms.

Keywords: Air pollution, Endocrinology, Pediatrics

Highlights

There is growing evidence for a relationship between ambient air pollution and altered metabolic and endocrine systems in children. Further studies considering multipollutant nature of air pollution and additional outcomes are needed to demonstrate the underlying mechanism.

Introduction

Exposure to ambient air pollution (AP) increases morbidity and mortality and contributes substantially to the global burden of disease [1]. AP increases the risk of respiratory and cardiovascular diseases, strokes, allergic diseases, diabetes, and autoimmune diseases in adults [2-5]. AP is generated mainly from fossil fuel combustion, industrial processes, construction work, cigarette smoking, and consumer products and is naturally produced by wildfires, volcanoes, and thunderstorms [6]. The components of AP are complex and mixed with natural or artificial substances and contain large volumes of gases, liquid droplets, or solid particles. Gaseous components of AP include ozone (O3), nitrogen dioxide (NO2), sulfur dioxide (SO2), carbon monoxide, and carbon dioxide. Particulate matter (PM) includes dust, soil, organic acids, and metals, and some of these compounds have similar effects to endocrine-disrupting chemicals (EDCs) [6]. PM is categorized based on particle size –PM10 (smaller than 10 μm), PMcoarse (ranging from 2.5 μm to 10 μm), PM2.5 (smaller than 2.5 μm), and ultrafine PM (smaller than 0.1 μm). Traffic-related AP contributes significantly to outdoor AP, especially in urban settings, and is comprised of nitrogen oxides (NOx) of nitric oxide (NO) and NO2 and PM. In children, there is growing evidence that AP can affect the endocrine system. In this review, we discussed the effects of ambient APs on childhood endocrinologic disorders and possible associated mechanisms.

Association between AP and childhood endocrinologic disorders in human studies

1. Type 1 diabetes mellitus

Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by destruction of insulin-producing pancreatic islet beta cells. The exact etiology is understood incompletely, although disease development is influenced by both genetic and nongenetic factors, including infections, early infant diet, gut microbiome, and vitamin D deficiency [7]. It recently has been suggested that environmental chemicals and AP are associated with development of T1DM [8]. Previous case-control studies of children with T1DM showed a relationship between development of T1DM and concentrations of O3 [9] and PM10, especially in children younger than 5 years [10]. Research has found that households with diabetes were more likely to be exposed to secondhand smoke than nondiabetic households [9].
Human studies of the relationship between ambient AP and T1DM in pediatric patients have investigated age at onset, incidence, or disease exacerbation of T1DM (Table 1). Three studies that evaluated the effect of prenatal ambient AP exposure showed inconsistent results [11-13]. A Swedish observational study found that NOx exposure during the third trimester of pregnancy was associated with development of T1DM in children [11]. However, in recent studies, exposure to NO or NO2 had no significant effect on the incidence of T1DM [12,13]. Results of the effects of maternal O3 exposure consistently showed that O3 exposure was associated with increased incidence of T1DM in children [11-13]. However, the associations between PM10 [13] and PM2.5 exposure [12,13] during gestation and incidence of T1DM in children were not significant.
Results from postnatal exposure studies that assessed air pollutants were inconsistent [14-19]. Most previous studies showed no relationship between exposure to NOx or NO2 during the postnatal period and incidence [12,15,19], or age at onset [16] of T1DM or serum hemoglobin A1c (HbA1c) level among patients with T1DM [17,18], with the exception of one study reporting that greater exposure to NO2 accelerated onset of T1DM in early childhood (0–4 years of age) [14]. The increased annual mean concentration of O3 during childhood or adolescence accelerated the mean age at onset of T1DM [15], although no direct relationship was observed [16]. Other studies reported no association [17] or an inverse association [18] with serum HbA1c level among patients with T1DM, suggesting a therapeutic effect of O3 through blood glucose reduction, because moderate oxidative stress induced by O3 activated both free antioxidants and antioxidative enzymes [20]. Postnatal PM10 exposure was associated with the increased incidence of T1DM in children [15,19]. The effect on mean age at onset of T1DM of PM10 exposure varied from no association [16] to younger [14] or older [15]. The annual mean concentration of PM10 was not related to serum HbA1c level in patients with T1DM [17,18]. Further, PM2.5 exposure was not related to the incidence of T1DM [12] or the age of onset in patients with T1DM [14].

2. Childhood obesity

Childhood obesity can be promoted by multiple factors, primarily due to an imbalance between energy intake and consumption. There is growing evidence that environmental chemical exposure can act as an "obesogen" and contribute to excessive weight gain [21]. Previous studies revealed that maternal exposure to combustion-derived polycyclic aromatic hydrocarbons [22] and cigarette smoke during pregnancy [23] was associated with an increased risk of childhood obesity.
To date, results from human epidemiological studies on the relationship between ambient AP and childhood obesity have been mixed and inconclusive (Table 2). Further, the results of research on the effects of prenatal exposure to ambient AP on infant or child weight gain were inconsistent [24-30]. PM2.5 exposure during gestation was not associated with weight gain in infancy [24] or adiposity [25,30] or body mass index (BMI) trajectory [28,29] during early- or midchildhood; however, a positive association between prenatal PM2.5 exposure and childhood overweight or obesity [26] or adiposity [27] was reported. While most previous studies have set the specific exposure time and investigated the impact of the average concentration during that period, one cohort study used Bayesian distributed lag interaction models to identify prenatal periods that could be sensitive windows influencing childhood obesity by sex [27]. This research suggested that increased exposure to PM2.5 in midpregnancy was associated with increased fat mass and higher BMI z-score (body size) among boys, and higher exposure to PM2.5 from early-to-mid pregnancy was associated with increased waist-to-hip ratio (body shape). Moreover, another cohort study simultaneously assessed the impact of 4 air pollutants (PM10, SO2, NO, and NO2) during prenatal and postnatal periods using a multipollutant model to account for collinearity between pollutants and exposure periods and showed that higher SO2 in utero and in childhood was associated with lower BMI, while higher NO2 in childhood was associated with higher BMI among boys [30].
Different studies have shown a significant association between postnatal exposure to ambient AP and BMI [25,28,30-34] and the risk for becoming overweight and obese [26,35-41], while no relationship with BMI [42] or a negative association with BMI or obesity-related parameters [25,30] has been reported. Longitudinal U.S. cohort studies have shown a positive association between higher traffic density within 150 m around a residence and BMI at 18 years of age [31], although the perimeter was not associated with early- and mildchildhood obesity-related parameters [25,42]. Most studies have shown a positive relationship between postnatal NOx or NO2 exposure and obesity-related parameters and reported a greater increase in BMI [28,30,32-34] and attained BMI at 10 years [28,32] and 18 years [33] of age and a higher risk of being overweight or obese [35-37,39-41], although an Italian cohort study did not report any significant results [42].
In regard to O3 exposure, a positive association with overweight or obesity was reported in 2 Chinese cross-sectional studies [35,39]. PM10 exposure was positively associated with risk of being overweight or obese in childhood in some studies [35,39,41], but no relationship was found between PM10 exposure and obesity-related parameters or the risk of being overweight or obese during childhood in other studies [30,36,39,42]. Effects of postnatal PM2.5 exposure were associated with a higher BMI [34,40] or risk of being overweight or obese [37,38,41]; however a negative [25] or no association [36,42] with obesity-related parameters also was observed. Several studies have shown a sex difference [27] or a strong association between ambient AP and obesity in boys compared with girls [30,39,40], which might be linked to sex differences in biological responses to environmental chemicals and social and behavioral factors. Recent cross-sectional studies showed a significant association of increased risk of obesity in school-aged children by measuring exposure to ambient AP based on the nearest air monitoring station at school instead of home, where children spend most of their time [37-40].

3. Insulin resistance

An increase in the prevalence of type 2 diabetes mellitus (T2DM) is a global concern for mortality and disability in adults [43]. In addition to traditional risk factors such as poor diet, low physical activity, and socioeconomic status, recent studies have suggested that ambient AP exposure can contribute to T2DM development. Although several systematic reviews and meta-analyses have revealed a relationship between ambient AP exposure and T2DM risk in adults [44-47], no reports have assessed the risk of T2DM due to ambient AP exposure in children. Several studies have evaluated the effects of AP and the association with diabetes development in children and insulin resistance.
Three reports investigating the effect of prenatal exposure to ambient AP on insulin resistance showed inconsistent results (Table 3) [48-50]. Prenatal exposure to NO2 was not associated with cord plasma insulin level in infants [48], which might be a risk factor of metabolic disease later in life. However, the exposure paradoxically was associated with fasting glucose, insulin, and homeostatic model assessment for insulin resistance (HOMA-IR) in adolescents between 10–15 years of age [50]. Higher prenatal PM2.5 and PM10 exposures were associated with increased cord plasma insulin level [48], and prenatal and perinatal PM2.5 exposure was associated with an annual increase in serum HbA1c level in girls from 4–5 years to 6–7 years of age [49]. These 2 studies commonly reported that the second trimester of pregnancy was an exposure window associated with increased serum HbA1c level later in childhood.
Most previous studies have reported a positive association of higher rates of exposure to NO2 during childhood and adolescence with increased HOMA-IR [51,52] or insulin resistance [34,53] and increased fasting glucose level [53,54], with the exception of one report that showed a negative association [50]. Exposure to PM10 was associated with increased HOMA-IR in 2 German studies [51,52], although exposure was not associated with fasting glucose level in a Chinese study [54]. Results from studies on exposure to PM2.5 have ranged from negative [25] or no relationship with HOMA-IR [51,52], to a positive association with lower insulin sensitivity [53]. Two studies in the United States that included overweight or obese children used the frequently sampled intravenous glucose tolerance test and revealed that higher NO2 and PM2.5 were associated with higher insulin resistance and secretion, as measured by higher glycemic values [34,53], and a faster decline in insulin sensitivity during follow-up, independent of adiposity [34]. These findings suggest that increased AP exposure is an independent risk factor for β-cell exhaustion. Only one intervention and prospective study was conducted in adolescents who underwent laparoscopic adjustable gastric banding due to severe obesity. That study found that increased exposure to NO2 attenuated the magnitude of HbA1c reduction, a known metabolic benefit of gastric banding [55].

4. Thyroid dysfunction

Several environmental chemicals have structures similar to those of thyroid hormones. These chemicals include polychlorinated biphenyls, triclosan, polybrominated diphenyl ethers, and bisphenol A and can reduce circulating levels of thyroid hormone by interfering with thyroid hormone metabolism, transport, and clearance [56]. Findings from previous studies suggest that airborne persistent organic pollutants [57], cadmium [58], and exposure to active and passive cigarette smoke [59] can affect thyroid hormone regulation and function in neonates and adults.
A few human studies on the impact of PM pollution exposure on thyroid function have been conducted, although these studies have focused on the relationship between maternal exposure and neonatal thyroid function (Table 4) [60-63]. Maternal exposure to PM2.5 in the third trimester was inversely associated with cord blood thyroid-stimulating hormone (TSH) level and the free thyroxine (T4)/free triiodothyronine (T3) ratio and was positively associated with cord blood free T3 [60], but no association between maternal PM2.5 exposure in the first trimester and neonatal TSH level was found [62]. These 2 studies identified cord blood free T4 [60] and maternal free T4 in the second trimester [62] as a partial mediator that linked prenatal PM2.5 exposure and birth weight of newborns. Another study evaluated the susceptible prenatal window period in which PM2.5 exposure at the end of the first trimester and PM10 exposure throughout most of the pregnancy were associated with higher total newborn T4 concentration in heel-prick blood spot test [61]. A cross-sectional study in China showed that high PM2.5 exposure during pregnancy was associated with increased incidence of congenital hypothyroidism in offspring [63]. However, no studies have investigated the association between postnatal PM exposure and thyroid function in childhood or adolescence.

5. Pubertal development

Adiposity and exposure to EDCs have been suggested as important factors in the association between environmental factors and pubertal onset, particularly with respect to the current decline in the average age at onset of puberty in girls [64]. For example, early life tobacco exposure [65] or secondhand and prenatal smoke exposure [66] is associated with earlier pubertal maturation.
A few epidemiological studies investigating AP and pubertal development in children have shown inconsistent results (Table 5) [67-70]. An epidemiological study in Hong Kong showed differences between boys and girls concerning the type of AP and window time, which was related to later pubertal development, and the results were based on multipollutant analysis [67]. Higher PM10 exposure in utero and in infancy lowered the pubertal stage among girls, whereas higher SO2 and NO2 exposure in utero and during childhood lowered the pubertal stage among boys. In contrast, girls that lived within 150 m from major roads or highways developed pubic hair several months earlier than those that lived further away [68]. Moreover, exposure to a higher concentration of PM10 in the pre-menarche period was associated with lower menarche age in Korean adolescents, and the risk of early menarche was higher when the exposure period was shorter, indicating that the neuroendocrine system becomes susceptible to PM10 exposure at the time of menarche [69]. However, no relationship between air pollutants (NO2, O3, PM10, and PM2.5) and serum sex hormone levels in 10-year-old children was reported [70].

Possible mechanisms

1. The immune system and inflammatory responses

The mechanism by which air pollutants contribute to endocrinologic disorders is not known, although altered immune responses and inflammatory reactions have been suggested as possibilities [71]. Inhaled AP comes into contact with alveolar macrophages and induces proinflammatory cytokine production as well as oxidative stress. These cytokines can spill over into systemic circulation and affect distant tissues, promoting autoimmune responses and metabolic dysfunction [71]. PM components such as transition metals, lipopolysaccharides, and O3 can infiltrate into the systemic vasculature and activate toll-like receptors [72]. Signal transduction, including transcription factor nuclear factor kappa B, is activated and promotes the production of proinflammatory cytokines (interleukin [IL]-4, IL-6, IL-8, and tumor necrosis factor [TNF]-α) [73,74], which leads to chronic inflammation and low-grade oxidative stress in the body. Particularly, PM2.5 modulates cytokine production and changes the balance between TNF-α and the production of anti-inflammatory IL-10 molecules in adolescents [75]. Increased IL-10 and reduced TNF-α levels serve as a biomarker for T helper 1 cell-mediated immune suppression and exacerbation of T helper 2-mediated humoral immune responses, contributing to the development of autoimmune diseases such as T1DM.

2. The neuroendocrine system

The neuroendocrine system can be important in AP-induced endocrine dysfunction. An experimental study revealed that exposure to prenatal diesel exhaust induced direct neuroinflammation and neuronal structural changes in the feeding centers of the hypothalamus and increased vulnerability to a high-fat diet and weight gain later in life [76], suggesting direct alteration of the central nervous system. AP also can activate stress-responsive regions in the brain through the sympathetic efferent and the hypothalamus-pituitary-adrenal axes [77]. For example, O3 inhalation evokes lung inflammation that induces the activation of nucleus tractus solitarius neurons through the vagus nerves and promotes neuronal activation in stress-responsive regions of the central nervous system in mice.78) O3 exposure also increased circulating corticosterone and cortisol levels in humans [79]. These results show that increased neuronal stress response can affect metabolic regulation.

3. Placental development and epigenetic modulation

Environmental stimuli or challenges during critical periods can alter placental development to the extent that the placenta could adapt by alternating transporter expression and activity to maintain fetal growth or by epigenetic regulation of placental gene expression, resulting in detrimental consequences later in life [80]. Inadequate placental perfusion affects fetal growth of the endocrine system in utero. AP exposure during pregnancy contributes to an anti-angiogenic profile, which could decrease placental weight [81] and is associated with increased inflammatory markers [82,83].
The epigenetic repression and activation of gene transcription are affected by environmental stimuli, such as nutrition, light, and endocrine disruptors [84]. There is increasing evidence that epigenetic mechanisms play an important role in the development of T1DM [85,86] and also in neuroendocrine system regulation, which can impact the timing of puberty [84,87]. In addition, a recent study showed that in utero exposure to polycyclic aromatic hydrocarbons induces offspring obesity by hypomethylation of peroxisome proliferator-activated receptorgamma and by subsequent activation of various genes associated with adipogenesis in adipose tissue of the offspring. Exposure to PM also induces deoxyribonucleic acid methylation [88], which could be a partial mediator between PM and adverse health outcomes.

4. Obesity and insulin resistance

The effects of increased AP exposure on the development of obesity and insulin resistance are complex and multifactorial. Excess AP is associated with decreased outdoor activities and reduced energy expenditure, which increases the likelihood of obesity. Alternations in mitochondrial number and size, downregulated brown adipocyte-specific genes in thermogenesis, and energy expenditure also are induced by PM exposure [89]. In addition, exposure to AP can alter the basal metabolism, including white adipose tissue inflammation, inhibition of lipolysis, and redistribution of adipose tissue in the viscera [89-92], playing a key role in the development of insulin resistance, diabetes, and systemic inflammatory effects. Endothelial dysfunction after AP exposure [93,94] is implicated in reduced peripheral glucose uptake. O3 also creates free oxygen radicals that directly contribute to beta-cell damage [95].

5. Thyroid system

Research has indicated that oxidative stress, inflammatory status, alterations to the neuroendocrine system, and inadequate placental adaptation can affect the thyroid. For example, increased glucocorticoid activity markers inhibit TSH release. Increased thyroid-binding globulin was observed after exposure to cigarette smoke, which could be transferred via the placenta, and can lead to higher total T4 level and lower free T4 level [96]. Cigarette smoke was associated with stimulated conversion of T4 to T3 by activities that promoted type 2 deiodinase in tissues, leading to decreased free T4 level and increased free T3 level [97]. A recent experimental study in female rats found that PM2.5 exposure could reduce circulating thyroid hormone levels by interrupting thyroid hormone biosynthesis, biotransformation, and transport; inducing oxidative stress and inflammatory responses; and ultimately activating the hypothalamic-pituitary-thyroid axis and inducing the production of hepatic transthyretin [98].

6. Pubertal development

The mechanisms that link AP and pubertal development or sex hormones have not been investigated, although they are expected to mimic the effects of EDCs. These effects could be caused by several mechanisms that impact puberty either peripherally or centrally; the agents could act as agonists of estrogen receptors or antagonists of androgen receptors and as obesogens, which alter the metabolic and peripheral hormones and can affect genes or the hypothalamic-pituitary-gonad axis [99].

Conclusion

Human studies provide considerable evidence of short-and long-term exposures to ambient APs, such as PM, NO2, and NOx, which affect the endocrine system and contribute to the development of childhood T1DM, obesity, and insulin resistance, although conflicting results have been reported. However, there is little evidence on the effect on thyroid function on onset of puberty. Altered immune response, oxidative stress, neuroinflammation, inadequate placental development, and epigenetic modulation are some of the underlying factors that have been identified and investigated. However, it is difficult to demonstrate causality because results from human studies are heterogeneous due to different study designs, timing and degree of exposure, methodology of exposure, and outcome measurements. Additionally, ambient APs are composed of various microscopic solids or liquid droplets and EDCs, and the extent to which airborne EDCs contribute to the overall burden on the human body is unknown. To further understand the mechanisms that link AP and the risk of endocrine disorders in children, future studies should consider the multipollutant nature of the mixture and the varying chemical composition, which could lead to different toxicities according to sex or susceptible window. Studies on additional outcomes such as changes in metabolomics and the microbiome in the intestine and central nervous system are needed to evaluate the biological pathway. Future research can help prevent environmental toxicity and improve treatment approaches for endocrine disorders.

Notes

Conflicts of interest

No potential conflict of interest relevant to this article was reported.

References

1. Cohen AJ, Brauer M, Burnett R, Anderson HR, Frostad J, Estep K, et al. Estimates and 25-year trends of the global burden of disease attributable to ambient air pollution: An analysis of data from the global burden of diseases study 2015. Lancet. 2017; 389:1907–18.
crossref
2. Badyda A, Gayer A, Czechowski PO, Maje wski G, Dąbrowiecki P. Pulmonary function and incidence of selected respiratory diseases depending on the exposure to ambient pm(10). Int J Mol Sci. 2016; 17:1954.
crossref
3. Baldacci S, Maio S, Cerrai S, Sarno G, Baïz N, Simoni M, et al. Allergy and asthma: effects of the exposure to particulate matter and biological allergens. Respir Med. 2015; 109:1089–104.
crossref
4. Renzi M, Cerza F, Gariazzo C, Agabiti N, Cascini S, Di Domenicantonio R, et al. Air pollution and occurrence of type 2 diabetes in a large cohort study. Environ Int. 2018; 112:68–76.
crossref
5. Brook RD, Bard RL, Morishita M, Dvonch JT, Wang L, Yang HY, et al. Hemodynamic, autonomic, and vascular effects of exposure to coarse particulate matter air pollution from a rural location. Environ Health Perspect. 2014; 122:624–30.
crossref
6. Darbre PD. Overview of air pollution and endocrine disorders. Int J Gen Med. 2018; 11:191–207.
crossref
7. Vehik K, Dabelea D. The changing epidemiology of type 1 diabetes: why is it going through the roof? Diabetes Metab Res Rev. 2011; 27:3–13.
crossref
8. Howard SG. Exposure to environmental chemicals and type 1 diabetes: an update. J Epidemiol Community Health. 2019; 73:483–8.
crossref
9. Hathout EH, Beeson WL, Ischander M, Rao R, Mace JW. Air pollution and type 1 diabetes in children. Pediatr Diabetes. 2006; 7:81–7.
crossref
10. Hathout EH, Beeson WL, Nahab F, Rabadi A, Thomas W, Mace JW. Role of exposure to air pollutants in the development of type 1 diabetes before and after 5 yr of age. Pediatr Diabetes. 2002; 3:184–8.
crossref
11. Malmqvist E, Larsson HE, Jönsson I, Rignell-Hydbom A, Ivarsson SA, Tinnerberg H, et al. Maternal exposure to air pollution and type 1 diabetes--accounting for genetic factors. Environ Res. 2015; 140:268–74.
12. Elten M, Donelle J, Lima I, Burnett RT, Weichenthal S, Stieb DM, et al. Ambient air pollution and incidence of earlyonset paediatric type 1 diabetes: a retrospective populationbased cohort study. Environ Res. 2020; 184:109291.
crossref
13. Taha-Khalde A, Haim A, Karakis I, Shashar S, Biederko R, Shtein A, et al. Air pollution and meteorological conditions during gestation and type 1 diabetes in offspring. Environ Int. 2021; 154:106546.
crossref
14. B e yerlein A, Krasmann M, Thiering E, Kusian D, Markevych I, D'Orlando O, et al. Ambient air pollution and early manifestation of type 1 diabetes. Epidemiology. 2015; 26:e31–2.
crossref
15. Di Ciaula A. Type i diabetes in paediatric age in apulia (italy): incidence and associations with outdoor air pollutants. Diabetes Res Clin Pract. 2016; 111:36–43.
crossref
16. R osenbauer J, Tamayo T, B ächle C, Stahl-Pehe A, Landwehr S, Sugiri D, et al. Re: Ambient air pollution and early manifestation of type 1 diabetes. Epidemiology. 2016; 27:e25–6.
17. Tamayo T, Rathmann W, Stahl-Pehe A, Landwehr S, Sugiri D, Krämer U, et al. No adverse effect of outdoor air pollution on hba1c in children and young adults with type 1 diabetes. Int J Hyg Environ Health. 2016; 219:349–55.
crossref
18. Lanzinger S, Rosenbauer J, Sugiri D, Schikowski T, Treiber B, Klee D, et al. Impact of long-term air pollution exposure on metabolic control in children and adolescents with type 1 diabetes: results from the dpv registry. Diabetologia. 2018; 61:1354–61.
crossref
19. Michalska M, Zorena K, Wąż P, Bartoszewicz M, BrandtVarma A, Ślęzak D, et al. Gaseous pollutants and particulate matter (pm) in ambient air and the number of new cases of type 1 diabetes in children and adolescents in the pomeranian voivodeship, poland. Biomed Res Int. 2020; 2020:1648264.
crossref
20. Sagai M, Bocci V. Mechanisms of action involved in ozone therapy: is healing induced via a mild oxidative stress? Med Gas Res. 2011; 1:29.
crossref
21. Holtcamp W. Obesogens: an environmental link to obesity. Environ Health Perspect. 2012; 120:a62–8.
crossref
22. Rundle A, Hoepner L, Hassoun A, Oberfield S, Freyer G, Holmes D, et al. Association of childhood obesity with maternal exposure to ambient air polycyclic aromatic hydrocarbons during pregnanc y. Am J Epidemiol. 2012; 175:1163–72.
23. Ino T, Shibuya T, Saito K, Inaba Y. Relationship between body mass index of offspring and maternal smoking during pregnancy. Int J Obes (Lond). 2012; 36:554–8.
crossref
24. Fleisch AF, Rifas-Shiman SL, Koutrakis P, Schwartz JD, Kloog I, Melly S, et al. Prenatal exposure to traffic pollution: associations with reduced fetal growth and rapid infant weight gain. Epidemiology. 2015; 26:43–50.
25. Fleisch AF, Luttmann-Gibson H, Perng W, Rifas-Shiman SL, Coull BA, Kloog I, et al. Prenatal and early life exposure to traffic pollution and cardiometabolic health in childhood. Pediatr Obes. 2017; 12:48–57.
crossref
26. Mao G, Nachman RM, Sun Q, Zhang X, Koehler K, Chen Z, et al. Individual and joint effects of early-life ambient exposure and maternal prepregnancy obesity on childhood overweight or obesity. Environ Health Perspect. 2017; 125:067005.
27. Chiu YM, Hsu HL, Wilson A, Coull BA, Pendo MP, Baccarelli A, et al. Prenatal particulate air pollution exposure and body composition in urban preschool children: examining sensitive windows and sex-specific associations. Environ Res. 2017; 158:798–805.
crossref
28. Kim JS, Alderete TL, Chen Z, Lurmann F, Rappaport E, Habre R, et al. Longitudinal associations of in utero and early life near-roadway air pollution with trajectories of childhood body mass index. Environ Health. 2018; 17:64.
crossref
29. Fleisch AF, Aris IM, Rifas-Shiman SL, Coull BA, LuttmannGibson H, Koutrakis P, et al. Prenatal exposure to traffic pollution and childhood body mass index trajectory. Front Endocrinol (Lausanne). 2018; 9:771.
crossref
30. Huang JV, Leung GM, Schooling CM. The association of air pollution with body mass index: evidence from hong kong's "children of 1997" birth cohort. Int J Obes (Lond). 2019; 43:62–72.
crossref
31. Jerrett M, McConnell R, Chang CC, Wolch J, Reynolds K, Lurmann F, et al. Automobile traffic around the home and attained body mass index: a longitudinal cohort study of children aged 10-18 years. Prev Med. 2010; 50 Suppl 1:S50–8.
crossref
32. Jerrett M, McConnell R, Wolch J, Chang R, Lam C, Dunton G, et al. Traffic-related air pollution and obesity formation in children: a longitudinal, multilevel analysis. Environ Health. 2014; 13:49.
crossref
33. McConnell R, Shen E, Gilliland FD, Jerrett M, Wolch J, Chang CC, et al. A longitudinal cohort study of body mass index and childhood exposure to secondhand tobacco smoke and air pollution: the southern california children's health study. Environ Health Perspect. 2015; 123:360–6.
crossref
34. Alderete TL, Habre R, Toledo-Corral CM, Berhane K, Chen Z, Lurmann FW, et al. Longitudinal associations between ambient air pollution with insulin sensitivity, β-cell function, and adiposity in los angeles latino children. Diabetes. 2017; 66:1789–96.
crossref
35. Dong GH, Qian Z, Liu MM, Wang D, Ren WH, Flick LH, et al. Ambient air pollution and the prevalence of obesity in Chinese children: the seven northeastern cities study. Obesity. 2014; 22:795–800.
crossref
36. Bloemsma LD, Wijga AH, Klompmaker JO, Janssen NAH, Smit HA, Koppelman GH, et al. The associations of air pollution, traffic noise and green space with overweight throughout childhood: the PIAMA birth cohort study. Environ Res. 2019; 169:348–56.
crossref
37. De Bont J, Casas M, Barrera-Gómez J, Cirach M, Rivas I, Valvi D, et al. Ambient air pollution and overweight and obesity in school-aged children in barcelona, spain. Environ Int. 2019; 125:58–64.
crossref
38. Guo Q, Xue T, Jia C, Wang B, Cao S, Zhao X, et al. Association between exposure to fine particulate matter and obesity in children: a national representative crosssectional study in China. Environ Int. 2020; 143:105950.
crossref
39. Zheng H, Xu Z, Wang Q, Ding Z, Zhou L, Xu Y, et al. Longterm exposure to ambient air pollution and obesity in school-aged children and adolescents in Jiangsu province of China. Environ Res. 2021; 195:110804.
crossref
40. Zhang Z, Dong B, Chen G, Song Y, Li S, Yang Z, et al. Ambient air pollution and obesity in school-aged children and adolescents: A multicenter study in China. Sci Total Environ. 2021; 771:144583.
crossref
41. De Bont J, Díaz Y, de Castro M, Cirach M, Basagaña X, Nieuwenhuijsen M, et al. Ambient air pollution and the development of overweight and obesity in children: a large longitudinal study. Int J Obes (Lond). 2021; 45:1124–32.
crossref
42. Fioravanti S, Cesaroni G, Badaloni C, Michelozzi P, Forastiere F, Porta D. Traffic-related air pollution and childhood obesity in an italian birth cohort. Environ Res. 2018; 160:479–86.
crossref
43. Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the global burden of disease study 2015. Lancet. 2016; 388:1545–602.
44. Balti EV, Echouffo-Tcheugui JB, Yako YY, Kengne AP. Air pollution and risk of type 2 diabetes mellitus: a systematic review and meta-analysis. Diabetes Res Clin Pract. 2014; 106:161–72.
crossref
45. Liu F, Chen G, Huo W, Wang C, Liu S, Li N, et al. Associations between long-term exposure to ambient air pollution and risk of type 2 diabetes mellitus: a systematic review and meta-analysis. Environ Pollut. 2019; 252:1235–45.
crossref
46. Yang BY, Fan S, Thiering E, Seissler J, Nowak D, Dong GH, et al. Ambient air pollution and diabetes: a systematic review and meta-analysis. Environ Res. 2020; 180:108817.
crossref
47. Eze IC, Hemkens LG, Bucher HC, Hoffmann B, Schindler C, Künzli N, et al. Association between ambient air pollution and diabetes mellitus in Europe and north America: systematic review and meta-analysis. Environ Health Perspect. 2015; 123:381–9.
crossref
48. Madhloum N, Janssen BG, Martens DS, Saenen ND, Bijnens E, Gyselaers W, et al. Cord plasma insulin and in utero exposure to ambient air pollution. Environ Int. 2017; 105:126–32.
crossref
49. Moody EC, Cantoral A, Tamayo-Ortiz M, Pizano-Zárate ML, Schnaas L, Kloog I, et al. Association of prenatal and perinatal exposures to particulate matter with changes in hemoglobin a1c levels in children aged 4 to 6 years. JAMA Netw Open. 2019; 2:e1917643.
50. Pedersen M, Halldorsson TI, Ketzel M, Grandström C, Raaschou-Nielsen O, Jensen SS, et al. Associations between ambient air pollution and noise from road traffic with blood pressure and insulin resistance in children from Denmark. Environ Epidemiol. 2019; 3:e069.
crossref
51. Thiering E, Cyrys J, Kratzsch J, Meisinger C, Hoffmann B, Berdel D, et al. Long-term exposure to traffic-related air pollution and insulin resistance in children: results from the GINIplus and LISAplus birth cohorts. Diabetologia. 2013; 56:1696–704.
crossref
52. Thiering E, Markevych I, Brüske I, Fuertes E, Kratzsch J, Sugiri D, et al. Associations of residential long-term air pollution exposures and satellite-derived greenness with insulin resistance in German adolescents. Environ Health Perspect. 2016; 124:1291–8.
crossref
53. Toledo-Corral CM, Alderete TL, Habre R, Berhane K, Lurmann FW, Weigensberg MJ, et al. Effects of air pollution exposure on glucose metabolism in los angeles minority children. Pediatr Obes. 2018; 13:54–62.
crossref
54. Zhang JS, Gui ZH, Zou ZY, Yang BY, Ma J, Jing J, et al. Longterm exposure to ambient air pollution and metabolic syndrome in children and adolescents: a national crosssectional study in china. Environ Int. 2021; 148:106383.
crossref
55. Ghosh R, Gauderman WJ, Minor H, Youn HA, Lurmann F, Cromar KR, et al. Air pollution, weight loss and metabolic benefits of bariatric surgery: a potential model for study of metabolic effects of environmental exposures. Pediatr Obes. 2018; 13:312–20.
crossref
56. Gore AC, Chappell VA, Fenton SE, Flaws JA, Nadal A, Prins GS, et al. Edc-2: the endocrine society's second scientific statement on endocrine-disrupting chemicals. Endocr Rev. 2015; 36:E1–150.
crossref
57. Abdelouahab N, Langlois MF, Lavoie L, Corbin F, Pasquier JC, Takser L. Maternal and cord-blood thyroid hormone levels and exposure to polybrominated diphenyl ethers and polychlorinated biphenyls during early pregnancy. Am J Epidemiol. 2013; 178:701–13.
crossref
58. Iijima K, Otake T, Yoshinaga J, Ikegami M, Suzuki E, Naruse H, et al. Cadmium, lead, and selenium in cord blood and thyroid hormone status of newborns. Biol Trace Elem Res. 2007; 119:10–8.
crossref
59. Soldin OP, Goughenour BE, Gilbert SZ, Landy HJ, Soldin SJ. Thyroid hormone levels associated with active and passive cigarette smoking. Thyroid. 2009; 19:817–23.
crossref
60. Janssen BG, Saenen ND, Roels HA, Madhloum N, Gyselaers W, Lefebvre W, et al. Fetal thyroid function, birth weight, and in utero exposure to fine particle air pollution: a birth cohort study. Environ Health Perspect. 2017; 125:699–705.
crossref
61. Howe CG, Eckel SP, Habre R, Girguis MS, Gao L, Lurmann FW, et al. Association of prenatal exposure to ambient and traffic-related air pollution with newborn thyroid function: findings from the children's health study. JAMA Netw Open. 2018; 1:e182172.
62. Wang X, Liu C, Zhang M, Han Y, Aase H, Villanger GD, et al. Evaluation of maternal exposure to pm(2.5) and its components on maternal and neonatal thyroid function and birth weight: a cohort study. Thyroid. 2019; 29:1147–57.
crossref
63. Shang L, Huang L, Yang W, Qi C, Yang L, Xin J, et al. Maternal exposure to PM(2.5) may increase the risk of congenital hypothyroidism in the offspring: a national database based study in China. BMC Public Health. 2019; 19:1412.
crossref
64. Parent AS, Franssen D, Fudvoye J, Gérard A, Bourguignon JP. Developmental variations in environmental influences including endocrine disruptors on pubertal timing and neuroendocrine control: revision of human observations and mechanistic insight from rodents. Front Neuroendocrinol. 2015; 38:12–36.
crossref
65. Maisonet M, Christensen KY, Rubin C, Holmes A, Flanders WD, Heron J, et al. Role of prenatal characteristics and early growth on pubertal attainment of British girls. Pediatrics. 2010; 126:e591–600.
crossref
66. Windham GC, Lum R, Voss R, Wolff M, Pinney SM, Teteilbaum SL, et al. Age at pubertal onset in girls and tobacco smoke exposure during pre- and postnatal susceptibility windows. Epidemiology. 2017; 28:719–27.
crossref
67. Huang JV, Leung GM, Schooling CM. The association of air pollution with pubertal development: Evidence from Hong Kong's "children of 1997" birth cohort. Am J Epidemiol. 2017; 185:914–23.
crossref
68. McGuinn LA, Voss RW, Laurent CA, Greenspan LC, Kushi LH, Windham GC. Residential proximity to traffic and female pubertal development. Environ Int. 2016; 94:635–41.
crossref
69. Jung EM, Kim HS, Park H, Ye S, Lee D, Ha EH. Does exposure to PM(10) decrease age at menarche? Environ Int. 2018; 117:16–21.
crossref
70. Zhao T, Triebner K, Markevych I, Standl M, Altug H, de Hoogh K, et al. Outdoor air pollution and hormoneassessed pubertal development in children: results from the GINIplus and LISA birth cohorts. Environ Int. 2021; 152:106476.
crossref
71. Ritz SA. Air pollution as a potential contributor to the 'epidemic' of autoimmune disease. Med Hypotheses. 2010; 74:110–7.
crossref
72. L i Z, Potts-Kant EN, Garantziotis S, Foster WM, Hollingsworth JW. Hyaluronan signaling during ozoneinduced lung injury requires tlr4, myd88, and tirap. PLoS One. 2011; 6:e27137.
crossref
73. Mirowsky JE, Carraway MS, Dhingra R, Tong H, Neas L, Diaz-Sanchez D, et al. Ozone exposure is associated with acute changes in inflammation, fibrinolysis, and endothelial cell function in coronary artery disease patients. Environ Health. 2017; 16:126.
crossref
74. Pilz V, Wolf K, Breitner S, Rückerl R, Koenig W, Rathmann W, et al. C-reactive protein (crp) and long-term air pollution with a focus on ultrafine particles. Int J Hyg Environ Health. 2018; 221:510–8.
crossref
75. Dobreva ZG, Kostadinova GS, Popov BN, Petkov GS, Stanilova SA. Proinflammatory and anti-inflammatory cytokines in adolescents from southeast bulgarian cities with different levels of air pollution. Toxicol Ind Health. 2015; 31:1210–7.
crossref
76. Bolton JL, Smith SH, Huff NC, Gilmour MI, Foster WM, Auten RL, et al. Prenatal air pollution exposure induces neuroinflammation and predisposes offspring to weight gain in adulthood in a sex-specific manner. FASEB J. 2012; 26:4743–54.
crossref
77. Kodavanti UP. Stretching the stress boundary: linking air pollution health effects to a neurohormonal stress response. Biochim Biophys Acta. 2016; 1860:2880–90.
crossref
78. Gackière F, Saliba L, Baude A, Bosler O, Strube C. Ozone inhalation activates stress-responsive regions of the cns. J Neurochem. 2011; 117:961–72.
crossref
79. Miller DB, Ghio AJ, Karoly ED, Bell LN, Snow SJ, Madden MC, et al. Ozone exposure increases circulating stress hormones and lipid metabolites in humans. Am J Respir Crit Care Med. 2016; 193:1382–91.
crossref
80. Yan Z, Zhang H, Maher C, Arteaga-Solis E, Champagne FA, Wu L, et al. Prenatal polycyclic aromatic hydrocarbon, adiposity, peroxisome proliferator-activated receptor (ppar) γ methylation in offspring, grand-offspring mice. PLoS One. 2014; 9:e110706.
crossref
81. van den Hooven EH, Pierik FH, de Kluizenaar Y, Hofman A, van Ratingen SW, Zandveld PY, et al. Air pollution exposure and markers of placental growth and function: the generation r study. Environ Health Perspect. 2012; 120:1753–9.
crossref
82. Lee PC, Talbott EO, Roberts JM, Catov JM, Sharma RK, Ritz B. Particulate air pollution exposure and c-reactive protein during early pregnancy. Epidemiology. 2011; 22:524–31.
crossref
83. Vadillo-Ortega F, Osornio-Vargas A, Buxton MA, Sánchez BN, Rojas-Bracho L, Viveros-Alcaráz M, et al. Air pollution, inflammation and preterm birth: a potential mechanistic link. Med Hypotheses. 2014; 82:219–24.
crossref
84. Lomniczi A, Wright H, Ojeda SR. Epigenetic regulation of female puberty. Front Neuroendocrinol. 2015; 36:90–107.
crossref
85. Zhao CN, Xu Z, Wu GC, Mao YM, Liu LN, Qian W, et al. Emerging role of air pollution in autoimmune diseases. Autoimmun Rev. 2019; 18:607–14.
crossref
86. Cerna M. Epigenetic regulation in etiology of type 1 diabetes mellitus. Int J Mol Sci. 2019; 21:36.
crossref
87. Rzeczkowska PA, Hou H, Wilson MD, Palmert MR. Epigenetics: a new player in the regulation of mammalian puberty. Neuroendocrinology. 2014; 99:139–55.
crossref
88. Sun B, Shi Y, Yang X, Zhao T, Duan J, Sun Z. DNA methylation: a critical epigenetic mechanism underlying the detrimental effects of airborne particulate matter. Ecotoxicol Environ Saf. 2018; 161:173–83.
crossref
89. Xu Z, Xu X, Zhong M, Hotchkiss IP, Lewandowski RP, Wagner JG, et al. Ambient particulate air pollution induces oxidative stress and alterations of mitochondria and gene expression in brown and white adipose tissues. Part Fibre Toxicol. 2011; 8:20.
crossref
90. Sun Q, Yue P, Deiuliis JA, Lumeng CN, Kampfrath T, Mikolaj MB, et al. Ambient air pollution exaggerates adipose inflammation and insulin resistance in a mouse model of diet-induced obesity. Circulation. 2009; 119:538–46.
crossref
91. Irigaray P, Ogier V, Jacquenet S, Notet V, Sibille P, Méjean L, et al. Benzo[a]pyrene impairs beta-adrenergic stimulation of adipose tissue lipolysis and causes weight gain in mice. A novel molecular mechanism of toxicity for a common food pollutant. FEBS J. 2006; 273:1362–72.
92. Zou MH. Is nad(p)h oxidase a missing link for air pollution-enhanced obesity? Arterioscler Thromb Vasc Biol. 2010; 30:2323–4.
crossref
93. Mills NL, Törnqvist H, Robinson SD, Gonzalez M, Darnley K, MacNee W, et al. Diesel exhaust inhalation causes vascular dysfunction and impaired endogenous fibrinolysis. Circulation. 2005; 112:3930–6.
crossref
94. Sun Q, Wang A, Jin X, Natanzon A, Duquaine D, Brook RD, et al. Long-term air pollution exposure and acceleration of atherosclerosis and vascular inflammation in an animal model. JAMA. 2005; 294:3003–10.
crossref
95. Butalia S, Kaplan GG, Khokhar B, Rabi DM. Environmental risk factors and type 1 diabetes: past, present, and future. Can J Diabetes. 2016; 40:586–93.
crossref
96. Fisher CL, Mannino DM, Herman WH, Frumkin H. Cigarette smoking and thyroid hormone levels in males. Int J Epidemiol. 1997; 26:972–7.
crossref
97. Gondou A, Toyoda N, Nishikawa M, Yonemoto T, Sakaguchi N, Tokoro T, et al. Effect of nicotine on type 2 deiodinase activity in cultured rat glial cells. Endocr J. 1999; 46:107–12.
crossref
98. Dong X, Wu W, Yao S, Li H, Li Z, Zhang L, et al. PM(2.5) disrupts thyroid hormone homeostasis through activation of the hypothalamic-pituitary-thyroid (HPT) axis and induction of hepatic transthyretin in female rats 2.5. Ecotoxicol Environ Saf. 2021; 208:111720.
crossref
99. Lee JE, Jung HW, Lee YJ, Lee YA. Early-life exposure to endocrine-disrupting chemicals and pubertal development in girls. Ann Pediatr Endocrinol Metab. 2019; 24:78–91.
crossref

Table 1.
Human studies investigating the relationship of ambient air pollution and type 1 diabetes in children
Country Study design Subjects, n (age) Exposure Exposure periods (age) Outcome (age) Findings Study
Prenatal
  Sweden Observational 84,039 NOx, O3, traffic density Prenatal T1DM incidence of offspring (8–14 years old) O3 during the second trimester and NOx in the third trimester were associated with increased T1DM risk among offspring. Malmqvist,[11] 2015
Canada Cohort 754,698 NO2, O3, PM2.5 Prenatal Incidence of T1DM (up to 6 years old) O3 exposure during the first trimester of pregnancy was associated with T1DM incidence (not NO2, PM2.5). Elten, [12] 2020
Israel Case-control 362 T1DM patients vs. 3,512 controls NO, NO2, O3, SO2, PM10, PM2.5 Prenatal T1DM incidence of offspring (0–18 years) O3 during gestation was associated with the T1DM in offspring (not NO, NO2, SO2, PM10, PM2.5). Taha- Khalde, [13] 2021
Postnatal
Germany Observational 671 T1DM patients (0–20 years old) NO2, PM10, PM2.5, PM2.5abs NA Age at onset of T1DM Higher exposure to PM10 and NO2 accelerates the onset of T1DM in 0–4 years old children (not PM2.5, PM2.5abs). Beyerlein, [14] 2015
Italy Observational 631,275 (0–14 years old) NOx, O3, PM10, CO 5-Year average levels T1DM incidence PM10 was associated with T1DM incidence rate (not O3, NOx, CO). Di Ciaula, [15] 2016
Mean age at T1DM onset was positively associated with PM10 and inversely with O3.
Germany Observational 6,807 T1DM patients (0–19 years old) NO2, O3, PM10 5-Year average levels Age at onset of T1DM Not associated with mean age at diagnosis Rosenbauer, [16] 2016
Germany Cross-sectional 771 T1DM patients (11–21 years old) NO2, O3, PM10 5-Year average levels HbA1c, daily insulin dose No adverse effect on metabolic control Tamayo, [17] 2016
Germany Cross-sectional 37,372 T1DM patients (0.5–20 years old) NO2, O3, PM10 5-Year average levels HbA1c, daily insulin dose Inverse relationship between O3 and HbA1c (not NO2, PM10) Lanzinger, [18] 2018
Canada Cohort 754,698 NO2, O3, PM2.5 Early childhood (0–5 years old) Incidence of T1DM (up to 6 years old) Not associated with T1DM incidence Elten, [12] 2020
Poland Observational 947,362 (0–18 years old) NO2, NOx, SO2, PM10abs, CO 2-Year average levels No. of new cases of T1DM PM10abs, SO2, and CO were correlated with the number of new cases of T1DM (not NO2, NOx). Michalska, [19] 2020

T1DM, type 1 diabetes mellitus; NO2, nitrogen dioxide; PM10, particulate matter with an aerodynamic diameter of <10 μm; PM2.5, particulate matter with an aerodynamic diameter of <2.5 μm; PM2.5abs, absorbance of PM2.5; NA, not available; NOx, nitrogen oxide; O3, ozone; CO, carbon monoxide; HbA1c, hemoglobin A1c; SO2, sulfur dioxide; PM10abs, absorbance of PM10.

Table 2.
Human studies investigating the relationship of ambient air pollution and childhood obesity
Country Study design Subjects, n (age) Exposure (average levels) Exposure periods (age) Outcome (age) Findings Study
Prenatal
  USA Cohort 2,115 PM2.5, BC, traffic density, roadway proximity Third trimester Birth weight, weight gain 6 months of age BC exposure, roadway proximity and traffic density: associated with greater weight gain in infancy (not PM2.5) Fleisch, [24] 2015
USA Cohort 1,418 PM2.5, BC, traffic density, roadway proximity Third trimester BMI, WC, skinfold thickness, total and truncal fat mass Not associated with childhood adiposity Fleisch, [25] 2017
USA Cohort 1,446 PM2.5 Prenatal Overweight or obesity (2-9 years old) Increase the risk of childhood overweight or obesity Mao, [26] 2017
USA Cohort 239 PM2.5 Prenatal BMI, fat mass, WC, WHR, skinfold thickness (4 years old) Higher PM2.5 exposure in mild-pregnancy was associated with increased fat mass and higher BMI among boys. Chiu, [27] 2017
Higher PM2.5 exposure from early-to-mid pregnancy was associated with WHR among girls.
USA Cohort 2,318 NOx, PM2.5 In utero 4-Year BMI trajectory and BMI at 10 years old Not associated with BMI at age 10 and the rate of growth over 4-year followup Kim, [28] 2018
USA Cohort 1,649 PM2.5, BC, traffic density Prenatal BMI trajectory (0.5–10 years old) Not associated with childhood BMI trajectory Fleisch, [29] 2018
Hong Kong Cohort 8,298 NO, NO2, SO2, PM10, In utero BMI (9, 11, 13, and 15 years old) Higher SO2 in utero was associated with lower BMI at 13 and 15 years Huang, [30] 2019
Postnatal
USA Cohort 2,889 (9-10 years old) Traffic density 8-Year average volume BMI (18 years old) Positive association with attained BMI at age 18 Jerrett, [31] 2010
USA Cohort 4,550 (5-7 years old) NOx, Traffic density 1-Year average levels BMI growth (10 years old) NOx (nonfreeway) was associated with BMI at age 10 and the rate of growth over 5-year follow-up Jerrett, [32] 2014
China Cross-sectional 30,056 NO2, O3, SO2, PM10 3-Year average levels Overweight and obesity (2–14 years old) Positive association with overweight and obesity Dong, [35] 2014
USA Cohort 3,318 (10 years old) NOx 8-Year average levels BMI growth (18 years old) Associated with an larger increase in BMI from age 10 to 18 and a higher attained BMI at age 18 McConnell, [33] 2015
USA Cohort 1,418 PM2.5, BC, traffic density, roadway proximity At birth, early- and midchildhood (median 3.3 and 7.7 years of age) BMI, WC, skinfold thickness, total and truncal fat mass Roadway proximity at birth was associated with greater BMI, WC and skinfold thickness in early childhood and greater BMI, total and truncal fat mass in mid childhood (not traffic density BC, PM2.5). Fleisch, [25] 2017
PM2.5 during the year prior to visit was negatively associated with BMI (not traffic density and BC).
USA Cohort 1,446 PM2.5 During first 2-year of age Overweight or obesity (2–9 years old) Increase the risk of childhood overweight or obesity Mao, [26] 2017
USA Cross-sectional 314 overweight or obese children (8-15 years old) NO2, PM2.5 1-Year average levels prior to visit BMI, SAAT and IAAT (at 18 years old) Higher NO2 and PM2.5 were associated with higher BMI, body fat percent, and central adiposity. Alderete, [34] 2017
USA Cohort 2,318 NOx, PM2.5 In infancy (<1) and childhood 4-Year BMI trajectory and BMI at 10 years old NOx exposure in infancy from freeway was associated with BMI at age 10 and the rate of growth over 4-year follow-up (not PM2.5) Kim, [28] 2018
Italy Cohort 719 NO2, NOx, PM10, PM2.5, PM2.5abs, PMcoarse, traffic density At birth, 4 and 8 years old BMI, WC, WHR (4 and 8 years old) Not associated with obesityrelated parameters Fioravanti, [42] 2018
Hong Kong Cohort 8,298 NO, NO2, SO2, PM10 In infancy and childhood BMI (9, 11, 13, and 15 years old) Higher SO2 in childhood were associated with lower BMI at 15 years. Huang, [30] 2019
Higher NO2 childhood was associated with higher BMI at 9, 13, 15 years among boys.
Netherlands Cohort 3,680 NO2, PM10, PM2.5, PM2.5abs 1-Year average levels of 3 periods of 2 weeks Overweight (3–17 years old) NO2 exposure increase the risk of being overweight (not PM2.5, PM10). Bloemsma, [36] 2019
Spain Cross-sectional 2,660 (7-10 years old) NO2, PM2.5, BC, Ultrafine particles 1-Week level during warm and cold seasons Overweight or obesity Increase the risk of being overweight or obesity De Bont, [37] 2019
China Cross-sectional 41,439 (6-17 years old) PM2.5 5-Year average level Obesity Increase the risk of obesity Guo, [38] 2020
China Cross-sectional 36,456 (9-17 years old) NO2, O3, PM10, PM2.5 3-Year average levels Obesity Higher PM2.5, NO2, and O3 exposure increased the risk of being obesity (not PM10). Zheng, [39] 2021
China Cross-sectional 44,718 (7-18 years old) NO2, PM1, PM2.5, PM10 1-Year average level BMI, WC, WHR, general and central obesity Associated with obesityrelated parameters Zhang, [40] 2021
Spain Longitudinal 416,955 NO2, PM10, PM2.5 PMcoarse 1-Year average level (2-5 years old) Overweight or obesity (15 years old) Increase the risk of developing overweight and obesity De Bont, [41] 2021

BMI, body mass index; NOx, nitrogen oxide; NO2, nitrogen dioxide; O3, ozone; SO2, sulfur dioxide; PM10, particulate matter with an aerodynamic diameter of <10 μm; PM2.5, particulate matter with an aerodynamic diameter of <2.5 μm; BC, black carbon; WC, waist circumference; SAAT, subcutaneous abdominal adipose tissue; IAAT, intra-abdominal adipose tissue; WHR, waist-to-hip ratio; PM2.5abs, absorbance of PM2.5; PMcoarse, coarse particles have an aerodynamic diameter ranging from 2.5 to 10 μm PM1, particulate matter with an aerodynamic diameter of <1 μm.

Table 3.
Human studies investigating the relationship of ambient air pollution and insulin resistance
Country Study design Subjects, n Exposure (average levels) Exposure periods (age) Outcome (age) Findings Study
Prenatal
  Belgium Observational 590 Mother-child pairs NO2, PM10, PM2.5 Prenatal Cord plasma insulin level Higher PM2.5 and PM10 was associated with increased cord plasma insulin levels (not NO2). Madhloun, [48] 2017
Mexico Observational 365 Mother-child pairs PM2.5 From 4 weeks prior to LMP to 52 weeks after) HbA1c (4–7 years old) Associated with an annual increase in HbA1c in girls from age 4–5 years to 6–7 years. Moody, [49] 2019
Denmark Cohort 629 NO2 Prenatal and postnatal (birth to age 7) Fasting glucose, insulin, HOMA-IR (10–15 years old) Inversely associated with fasting glucose, insulin, and HOMA-IR Pedersen, [50] 2019
Postnatal
Germany Cross-sectional 397 NO2, PM10, PM2.5, PM2.5abs, roadway proximity 1-Year average levels of 3 periods for 2 weeks HOMA-IR (at 10 years old) Exposure to NO2, PM10 and roadway proximity increase the HOMA-IR (not PM2.5, PM2.5abs). Thiering, [51] 2013
Germanry Cross-sectional 837 NO2, PM10, PM2.5, PM2.5abs 3 to 5-year average level HOMA-IR (at 15 years old) Exposure to NO2, PM10 increase the HOMA-IR (not PM2.5, PM2.5abs). Thiering, [52] 2016
USA Cohort 1,418 PM2.5, BC, traffic density, roadway proximity 3rd trimester, at birth, midchildhood (median 7.7 years of age) HOMA-IR at midchildhood (median age 7.7 years) PM2.5 exposure during the year prior to visit, traffic density and roadway proximity at birth were negatively associated with HOMA-IR. Fleisch, [25] 2017
USA Cohort 314 Overweight or obese children NO2, PM2.5 1-Year average level Results of FSIVGTT test (during follow-up and at 18 years old) Associated with a faster decline in insulin sensitivity and a lower insulin sensitivity at age 18 years Alderete, [34] 2017
USA Cross-sectional 429 Overweight or obese children NO2, NOx, O3, PM2.5 1-Year average level Results of FSIVGTT test (8–18 years old) PM2.5, NO2, and NOx was associated with higher fasting insulin, glucose, acute insulin response to glucose and lower insulin sensitivity (not O3). Toledo-Corral, [53] 2018
USA Prospective 75 Obese adolescents NO2, O3, PM2.5, roadway proximity 2-Year average levels HbA1c (postsurgery) NO2 was associated with less improvement in HbA1c (not PM2.5). Ghosh, [55] 2018
Denmark Cohort 629 NO2 Birth to age 7 Fasting glucose, insulin, HOMA-IR (10–15 years old) Inversely associated with fasting glucose, insulin, and HOMA-IR Pedersen, [50] 2019
China Cross-sectional 9,897 NO2, PM10, PM1, PM2.5 2-Year average levels Fasting glucose (10–18 years old) PM1 and NO2 exposures were associated with elevated fasting blood glucose (not PM10). Zhang, [54] 2021

NO2, nitrogen dioxide; PM10, particulate matter with an aerodynamic diameter of <10 μm; PM2.5, particulate matter with an aerodynamic diameter of <2.5 μm; PM2.5abs, absorbance of PM2.5; HOMA-IR, homeostatic model assessment for insulin resistance; PM1, particulate matter with an aerodynamic diameter of <1 μm; BC, black carbon; FSIVGTT, frequently sampled intravenous glucose tolerance test; O3, ozone; HbA1c, hemoglobin A1c; LMP, last menstrual period.

Table 4.
Human studies investigating the relationship of ambient air pollution and thyroid dysfunction
Country Study design Subjects Exposure Exposure period Outcome Findings Study
Prenatal
  Belgium Cohort 499 Mother and newborn pairs PM2.5 Third trimester TFT of mother and infant Decrease in cord blood TSH level and cord blood fT4/fT3 ratio Janssen, [60] 2017
USA Cohort 2050 Newborns NO, NO2, O3, PM10, PM2.5 Prenatal Total T4 levels of newborn PM2.5 and PM10 was associated with an increase in total T4 levels of heelstick blood spot (not NO, NO2, O3). Howe, [61] 2018
China Cohort 443 Mother and newborn pairs PM2.5 First trimester TFT of mother and infant Not associated with neonatal TSH Wang, [62] 2019
China Cross-sectional 15.1 Million newborns PM10, PM2.5 Prenatal Congenital hypothyroidism PM2.5 was associated with an increased risk of congenital hypothyroidism (not PM10). Shang, [63] 2019

PM2.5, particulate matter with an aerodynamic diameter of <2.5 μm; TFT, thyroid function test; TSH, thyroid-stimulating hormone; fT4, free thyroxine; fT3, free triiodothyronine; NO, nitric oxide; NO2, nitrogen dioxide; O3, ozone; PM10, particulate matter with an aerodynamic diameter of <10 μm.

Table 5.
Human studies investigating the relationship of ambient air pollution and pubertal development
Country Study design Subjects (age) Pollutants Exposure periods (age) Outcome (age) Findings Study
Prenatal
   Hong Kong Cohort 1,938 Girls and 2,316 boys NO, NO2, SO2, PM10 In utero Tanner stage (9–12 years old) Higher PM10 exposure in utero and in infancy was associated with later pubertal development among girls. Huang, [67] 2017
Higher SO2 and NO2 exposure in infancy and childhood were associated with later pubertal development among boys.
Postnatal
USA Cohort 437 Girls (6–8 years old) Traffic density, roadway proximity 9-Year annual average levels Tanner stage (6–8 years old) Associated with earlier onset (2–9 months) of pubic hair development (not breast development) McGuinn, [68] 2016
Hong Kong Cohort 1,938 Girls and 2,316 boys NO, NO2, SO2, PM10 In infancy (<2 years) and in childhood (2-<8 years) Tanner stage (9–12 years old) Higher PM10 exposure in utero and in infancy was associated with later pubertal development among girls. Huang, [67] 2017
Higher SO2 and NO2 exposure in infancy and childhood were associated with later pubertal development among boys.
Korea Cross-sectional 639 Girls (13–17 years old) PM10 1 to 3-year annual average level Age at menarche Associated with earlier onset of age at menarche Jung, [69] 2018
German Cohort 943 Girls and 1,002 boys NO2, O3, PM10, PM2.5 5-Year annual average levels Serum estradiol and testosterone levels (at 10 years old) Not associated with pubertal development defined by levels of estradiol and testosterone Zhao, [70] 2021

NO, nitric oxide; NO2, nitrogen dioxide; SO2, sulfur dioxide; PM10, particulate matter with an aerodynamic diameter of <10 μm.

TOOLS
Similar articles