The relationship between cadmium and childhood autism: a meta-analysis_Chinese Journal of Evidence-Based Medicine

Authors：

WANG Jiabin ^1,2 , WEI Lili ³ , WANG Meng ¹ , LIU Lu ⁴ , WANG Yanxia ² , WANG Chen ² , HU Yaguang ² , HUANG Peiyao ¹ , QIU Wenwen ⁴ , LIU Xudong ² , LI Fuyun ¹ ,  QIU Jie ^1,2 , YANG Kehu ³

1. School of Public Health, Lanzhou University, Lanzhou 730000, P.R.China;
2. Gansu Maternal and Child Health Care Center, Lanzhou 730050, P.R.China;
3. Evidence-Based Medicine Center, Lanzhou University, Lanzhou 730000, P.R.China;
4. Gansu University of Chinese Medicine, Lanzhou 730000, P.R.China;

Corresponding author：

QIU Jie, Email: qiujiegssfy@163.com

Keywords：

Autistic disorder; Children; Cadmium; Meta-analysis; Systematic review; Case-control study

DOI：

10.7507/1672-2531.201910119

Video：

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Objective To systematically review the relationship between cadmium (Cd) and childhood autism.Methods PubMed, EMbase, Web of Science, The Cochrane Library, CNKI, VIP, WanFang Data and CBM were electronically searched to collect case-control studies on the relationship between Cd and childhood autism from inception to July 2019. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then, meta-analysis was performed by using RevMan 5.3 software.Results A total of 8 case-control studies were included. The results of meta-analysis showed that whether the specimen was from whole blood, urine or hair, there were no correlations between Cd and childhood autism (MD_blood=0.17, 95% CI −0.06 to 0.39, P=0.15; MD_urine=−0.43, 95%CI −1.44 to 0.58, P=0.4; MD_hair=−0.08, 95%CI −0.52 to 0.36, P=0.72).Conclusions Current evidence shows that Cd concentration is not correlated with autism in children. Due to limited quality and quantity of the included studies, more high quality studies are required to verify above conclusions.

Citation： WANG Jiabin, WEI Lili, WANG Meng, LIU Lu, WANG Yanxia, WANG Chen, HU Yaguang, HUANG Peiyao, QIU Wenwen, LIU Xudong, LI Fuyun, QIU Jie, YANG Kehu. The relationship between cadmium and childhood autism: a meta-analysis. Chinese Journal of Evidence-Based Medicine, 2020, 20(6): 702-707. doi: 10.7507/1672-2531.201910119 Copy

1.	Duan G, Yao M, Ma Y, et al. Perinatal and background risk factors for childhood autism in central China. Psychiatry Res, 2014, 220(1-2): 410-417.
2.	戴琼, 徐海青, 汪鸿, 等. 2000-2016 年我国儿童孤独症流行病学研究论文的文献计量分析. 中国儿童保健杂志, 2017, 25(3): 271-274.
3.	殷道根, 何珍, 李敏, 等. 母乳喂养与儿童孤独症关系的 Meta 分析. 中国儿童保健杂志, 2018, 26(7): 754-757.
4.	毛萌, 杨慧明. 儿童保健临床研究进展. 中国实用儿科杂志, 2011, 26(6): 344-347.
5.	Qin YY, Jian B, Wu C, et al. A comparison of blood metal levels in autism spectrum disorder and unaffected children in Shenzhen of China and factors involved in bioaccumulation of metals. Environ Sci Pollut Res Int, 2018, 25(18): 17950-17956.
6.	Li H, Li H, Li Y, et al. Blood mercury, arsenic, cadmium, and lead in children with autism spectrum disorder. Biol Trace Elem Res, 2018, 181(1): 31-37.
7.	Saghazadeh A, Rezaei N. Systematic review and meta-analysis links autism and toxic metals and highlights the impact of country development status: Higher blood and erythrocyte levels for mercury and lead, and higher hair antimony, cadmium, lead, and mercury. Prog Neuropsychopharmacol Biol Psychiatry, 2017, 79(Pt B): 340-368.
8.	Hessabi M, Rahbar MH, Dobrescu I, et al. Concentrations of lead, mercury, arsenic, cadmium, manganese, and aluminum in blood of romanian children suspected of having autism spectrum disorder. Int J Environ Res Public Health, 2019, 16(13): E2303.
9.	Rahbar MH, Samms-Vaughan M, Dickerson AS, et al. Role of fruits, grains, and seafood consumption in blood cadmium concentrations of Jamaican children with and without autism spectrum disorder. Res Autism Spectr Disord, 2014, 8(9): 1134-1145.
10.	Mohammad R, Maureen S V, Aisha D, et al. Concentration of lead, mercury, cadmium, aluminum, arsenic and manganese in umbilical cord blood of Jamaican newborns. Int J Environ Res Public Health, 2015, 12(19): 4481-4501.
11.	杨克虎, 田金徽, 李伦. 网状 Meta 分析方法与实践. 北京: 中国医药科技出版社, 2018.
12.	Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol, 2010, 25(9): 603-605.
13.	Yorbik O, I Kurt A, Hasimi A, et al. Chromium, cadmium, and lead levels in urine of children with autism and typically developing controls. Biol Trace Elem Res, 2010, 135(13): 10-15.
14.	Adams JB, Audhya T, Mcdonough-Means S, et al. Toxicological status of children with autism vs. neurotypical children and the association with autism severity. Biol Trace Elem Res, 2013, 151(2): 171-180.
15.	Kern JK, Grannemann BD, Trivedi MH, et al. Sulfhydryl-reactive metals in autism. J Toxicol Environ Health A, 2007, 70(8): 715-721.
16.	Vergani L, Lanza C, Rivaro P, et al. Metals, metallothioneins and oxidative stress in blood of autistic children. Research in Autism Spectrum Disorders, 2011, 5(1): 286-293.
17.	De Palma G, Catalani S, Franco A, et al. Lack of correlation between metallic elements analyzed in hair by ICP-MS and autism. J Autism Dev Disord, 2012, 42(3): 342-353.
18.	Geier DA, Kern JK, King PG, et al. Hair toxic metal concentrations and autism spectrum disorder severity in young children. Int J Environ Res Public Health, 2012, 9(12): 4486-4497.
19.	俞慧强, 郑辉烈, 李悦, 等. Meta 分析发表偏倚诊断方法研究. 中国卫生统计, 2011, 28(4): 402-405.
20.	刘贤, 林穗方, 陈文雄, 等. 中国儿童孤独症谱系障碍患病率 Meta 分析. 中国儿童保健杂志, 2018, 26(4): 402-406, 429.
21.	Kogan MD, Strickland BB, Blumberg SJ, et al. A national profile of the health care experiences and family impact of autism spectrum disorder among children in the United States, 2005-2006. Pediatrics, 2008, 122(6): e1149-e1158.
22.	Montes G, Halterman JS. Child care problems and employment among families with preschool-aged children with autism in the United States. Pediatrics, 2008, 122(1): e202-e208.
23.	Seguí JD, Ortiz-Tallo M, Diego YD. Stress related factors in caregivers of children with autism: Over-load, psychopathology and health. Anales de Psicología, 2008, 24(1): 100-105.
24.	Mugno D, Ruta L, D'Arrigo VG, et al. Impairment of quality of life in parents of children and adolescents with pervasive developmental disorder. Health Qual Life Outcomes, 2007, 5(22): 234-236.
25.	Stuart M, Mcgrew JH. Care giver burden after receiving a diagnosis of an autism spectrum disorder. Res Aut Spect Dis, 2009, 3(1): 86-97.
26.	杨昱, 王曼. 学龄前孤独症儿童家庭的职业和经济负担调查. 中国临床心理学杂志, 2014, 22(2): 295-297, 361.
27.	袁燕. 镉对大鼠大脑皮质神经细胞毒性损伤的机制. 畜牧与兽医, 2016, 48(11): 91-94.
28.	陈龙, 周娟, 高伟, 等. 镐负荷大鼠一氧化氮和肿瘤坏死因子-α 释放在介导多器官机能活动障碍中的作用. 生理学报, 2003, 55(5): 535-540.
29.	Zawia NH, Lahiri DK, Cardozo-Pelaez F. Epigenetics, oxidative stress, and Alzheimer disease. Free Radic Biol Med, 2017, 46(9): 1241-1249.
30.	张斯蒙, 田沛茹, 辛芳冉. 镉暴露与高血压发病风险相关性的 Meta 分析. 中国循证医学杂志, 2018, 18(10): 1062-1069.
31.	黄慧, 李国慧, 李贵霞, 等. 健康儿童血清中钙, 镁, 铁, 锌, 铜, 铅, 镉 7 种元素检测结果研究. 中国实验诊断学, 2019, 23(3): 503-505.
32.	Jarup L. Hazards of heavy metal contamination. Br Med Bull, 2003, 68: 167-182.
33.	Jarup L, Akesson A. Current status of cadmium as an environmental health problem. Toxicol Appl Pharmacol, 2009, 238(3): 201-208.
34.	Berglund M, Akesson A, Nermell B, et al. Intestinal absorption of dietary cadmium in women depends on body iron stores and fiber intake. Environ Health Perspect, 1994, 102(12): 1058-1066.
35.	Zhang ZW, Moon CS, Watanabe T, et al. Background exposure of urban populations to lead and cadmium: comparison between China and Japan. Int Arch Occup Environ Health, 1997, 69(4): 273-281.
36.	Ikeda M, Zhang ZW, Shimbo S, et al. Urban population exposure to lead and cadmium in east and south-east Asia. Sci Total Environ, 2000, 249(1-3): 373-384.

1. Duan G, Yao M, Ma Y, et al. Perinatal and background risk factors for childhood autism in central China. Psychiatry Res, 2014, 220(1-2): 410-417.
2. 戴琼, 徐海青, 汪鸿, 等. 2000-2016 年我国儿童孤独症流行病学研究论文的文献计量分析. 中国儿童保健杂志, 2017, 25(3): 271-274.
3. 殷道根, 何珍, 李敏, 等. 母乳喂养与儿童孤独症关系的 Meta 分析. 中国儿童保健杂志, 2018, 26(7): 754-757.
4. 毛萌, 杨慧明. 儿童保健临床研究进展. 中国实用儿科杂志, 2011, 26(6): 344-347.
5. Qin YY, Jian B, Wu C, et al. A comparison of blood metal levels in autism spectrum disorder and unaffected children in Shenzhen of China and factors involved in bioaccumulation of metals. Environ Sci Pollut Res Int, 2018, 25(18): 17950-17956.
6. Li H, Li H, Li Y, et al. Blood mercury, arsenic, cadmium, and lead in children with autism spectrum disorder. Biol Trace Elem Res, 2018, 181(1): 31-37.
7. Saghazadeh A, Rezaei N. Systematic review and meta-analysis links autism and toxic metals and highlights the impact of country development status: Higher blood and erythrocyte levels for mercury and lead, and higher hair antimony, cadmium, lead, and mercury. Prog Neuropsychopharmacol Biol Psychiatry, 2017, 79(Pt B): 340-368.
8. Hessabi M, Rahbar MH, Dobrescu I, et al. Concentrations of lead, mercury, arsenic, cadmium, manganese, and aluminum in blood of romanian children suspected of having autism spectrum disorder. Int J Environ Res Public Health, 2019, 16(13): E2303.
9. Rahbar MH, Samms-Vaughan M, Dickerson AS, et al. Role of fruits, grains, and seafood consumption in blood cadmium concentrations of Jamaican children with and without autism spectrum disorder. Res Autism Spectr Disord, 2014, 8(9): 1134-1145.
10. Mohammad R, Maureen S V, Aisha D, et al. Concentration of lead, mercury, cadmium, aluminum, arsenic and manganese in umbilical cord blood of Jamaican newborns. Int J Environ Res Public Health, 2015, 12(19): 4481-4501.
11. 杨克虎, 田金徽, 李伦. 网状 Meta 分析方法与实践. 北京: 中国医药科技出版社, 2018.
12. Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol, 2010, 25(9): 603-605.
13. Yorbik O, I Kurt A, Hasimi A, et al. Chromium, cadmium, and lead levels in urine of children with autism and typically developing controls. Biol Trace Elem Res, 2010, 135(13): 10-15.
14. Adams JB, Audhya T, Mcdonough-Means S, et al. Toxicological status of children with autism vs. neurotypical children and the association with autism severity. Biol Trace Elem Res, 2013, 151(2): 171-180.
15. Kern JK, Grannemann BD, Trivedi MH, et al. Sulfhydryl-reactive metals in autism. J Toxicol Environ Health A, 2007, 70(8): 715-721.
16. Vergani L, Lanza C, Rivaro P, et al. Metals, metallothioneins and oxidative stress in blood of autistic children. Research in Autism Spectrum Disorders, 2011, 5(1): 286-293.
17. De Palma G, Catalani S, Franco A, et al. Lack of correlation between metallic elements analyzed in hair by ICP-MS and autism. J Autism Dev Disord, 2012, 42(3): 342-353.
18. Geier DA, Kern JK, King PG, et al. Hair toxic metal concentrations and autism spectrum disorder severity in young children. Int J Environ Res Public Health, 2012, 9(12): 4486-4497.
19. 俞慧强, 郑辉烈, 李悦, 等. Meta 分析发表偏倚诊断方法研究. 中国卫生统计, 2011, 28(4): 402-405.
20. 刘贤, 林穗方, 陈文雄, 等. 中国儿童孤独症谱系障碍患病率 Meta 分析. 中国儿童保健杂志, 2018, 26(4): 402-406, 429.
21. Kogan MD, Strickland BB, Blumberg SJ, et al. A national profile of the health care experiences and family impact of autism spectrum disorder among children in the United States, 2005-2006. Pediatrics, 2008, 122(6): e1149-e1158.
22. Montes G, Halterman JS. Child care problems and employment among families with preschool-aged children with autism in the United States. Pediatrics, 2008, 122(1): e202-e208.
23. Seguí JD, Ortiz-Tallo M, Diego YD. Stress related factors in caregivers of children with autism: Over-load, psychopathology and health. Anales de Psicología, 2008, 24(1): 100-105.
24. Mugno D, Ruta L, D'Arrigo VG, et al. Impairment of quality of life in parents of children and adolescents with pervasive developmental disorder. Health Qual Life Outcomes, 2007, 5(22): 234-236.
25. Stuart M, Mcgrew JH. Care giver burden after receiving a diagnosis of an autism spectrum disorder. Res Aut Spect Dis, 2009, 3(1): 86-97.
26. 杨昱, 王曼. 学龄前孤独症儿童家庭的职业和经济负担调查. 中国临床心理学杂志, 2014, 22(2): 295-297, 361.
27. 袁燕. 镉对大鼠大脑皮质神经细胞毒性损伤的机制. 畜牧与兽医, 2016, 48(11): 91-94.
28. 陈龙, 周娟, 高伟, 等. 镐负荷大鼠一氧化氮和肿瘤坏死因子-α 释放在介导多器官机能活动障碍中的作用. 生理学报, 2003, 55(5): 535-540.
29. Zawia NH, Lahiri DK, Cardozo-Pelaez F. Epigenetics, oxidative stress, and Alzheimer disease. Free Radic Biol Med, 2017, 46(9): 1241-1249.
30. 张斯蒙, 田沛茹, 辛芳冉. 镉暴露与高血压发病风险相关性的 Meta 分析. 中国循证医学杂志, 2018, 18(10): 1062-1069.
31. 黄慧, 李国慧, 李贵霞, 等. 健康儿童血清中钙, 镁, 铁, 锌, 铜, 铅, 镉 7 种元素检测结果研究. 中国实验诊断学, 2019, 23(3): 503-505.
32. Jarup L. Hazards of heavy metal contamination. Br Med Bull, 2003, 68: 167-182.
33. Jarup L, Akesson A. Current status of cadmium as an environmental health problem. Toxicol Appl Pharmacol, 2009, 238(3): 201-208.
34. Berglund M, Akesson A, Nermell B, et al. Intestinal absorption of dietary cadmium in women depends on body iron stores and fiber intake. Environ Health Perspect, 1994, 102(12): 1058-1066.
35. Zhang ZW, Moon CS, Watanabe T, et al. Background exposure of urban populations to lead and cadmium: comparison between China and Japan. Int Arch Occup Environ Health, 1997, 69(4): 273-281.
36. Ikeda M, Zhang ZW, Shimbo S, et al. Urban population exposure to lead and cadmium in east and south-east Asia. Sci Total Environ, 2000, 249(1-3): 373-384.

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