Skip to main content
SpringerLink
Log in

A case–control study on the relationship between urine trace element levels and autism spectrum disorder among Iranian children

  • Research Article
  • Published:
Environmental Science and Pollution Research Aims and scope Submit manuscript

Abstract

Autism spectrum disorder (ASD) is a type of neurodevelopmental disorder characterized mainly by qualitative deficiencies in social communication skills, accompanied by repetitive and restricted behavior patterns. This study was conducted to investigate the associations between the risk of ASD development in children and exposure to trace elements (arsenic (As), cadmium (Cd), chromium (Cr), cobalt (Co), copper (Cu), lead (Pb), nickel (Ni), and zinc (Zn)). Two groups of children, including 44 ASD and 35 typically developing (TD) children, were selected, and their fasting urine samples were obtained. The concentration levels of trace elements were assayed using ICP-MS. The results showed that as compared to the TD group, the concentration levels of As (p = 0.002) and Pb (p < 0.001) and also Cr (p < 0.001), Cu (p = 0.001), and Ni (p < 0.001) were significantly higher among ASD children. In terms of gender, boys with ASD showed elevated levels of Cr, Cu, Ni, and Pb, whereas the urine levels of As, Cr, Cu, Ni, and Pb were markedly higher among girls when compared to the non-ASD children. Under the logistic regression model, the risk difference for As, Co, Cr, Cu, Ni, Pb, and Zn remained significant when adjustment was applied for age and gender confounders.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Abd Wahil MS, Ja’afar MH, Isa ZM (2021): Assessment of urinary lead (Pb) and essential trace elements in autism spectrum disorder: a case-control study among preschool children in Malaysia. Biol Trace Element Res 200, 97-121

  • Adams JB, Audhya T, McDonough-Means S, Rubin RA, Quig D, Geis E, Gehn E, Loresto M, Mitchell J, Atwood S (2013) Toxicological status of children with autism vs. neurotypical children and the association with autism severity. Biol Trace Element Res 151:171–180

    Article  CAS  Google Scholar 

  • Adams J, Howsmon DP, Kruger U, Geis E, Gehn E, Fimbres V, Pollard E, Mitchell J, Ingram J, Hellmers R (2017) Significant association of urinary toxic metals and autism-related symptoms—a nonlinear statistical analysis with cross validation. PloS one 12:e0169526

    Article  Google Scholar 

  • Akyuzlu DK, Kayaalti Z, Soylemez E, Soylemezoglu T (2014) Association between autism and arsenic, lead, cadmium, manganese levels in hair and urine. J Pharm Pharmacol 2:140

    Google Scholar 

  • Albizzati A, More L, Di Candia D, Saccani M, Lenti C (2012) Normal concentrations of heavy metals in autistic spectrum disorders. Minerva Pediatr 64:27–31

    CAS  Google Scholar 

  • Al-Farsi YM, Waly MI, Al-Sharbati MM, Al-Shafaee MA, Al-Farsi OA, Al-Khaduri MM, Gupta I, Ouhtit A, Al-Adawi S, Al-Said MF (2013) Levels of heavy metals and essential minerals in hair samples of children with autism in Oman: a case–control study. Biol Trace Element Res 151:181–186

    Article  CAS  Google Scholar 

  • Baj J, Flieger W, Flieger M, Forma A, Sitarz E, Skórzyńska-Dziduszko K, Grochowski C, Maciejewski R, Karakuła-Juchnowicz H (2021) Autism spectrum disorder: trace elements imbalances and the pathogenesis and severity of autistic symptoms. Neurosci Biobehav Rev 1:117–132

    Article  Google Scholar 

  • Bhat S, Acharya UR, Adeli H, Bairy GM, Adeli A (2014) Autism: cause factors, early diagnosis and therapies. Rev Neurosci 25:841–850

    Google Scholar 

  • Bjørklund G (2013) The role of zinc and copper in autism spectrum disorders. Acta Neurobiol Exp (Wars) 73:225–236

    Google Scholar 

  • Bjørklund G, Skalny AV, Rahman MM, Dadar M, Yassa HA, Aaseth J, Chirumbolo S, Skalnaya MG, Tinkov AA (2018) Toxic metal (loid)-based pollutants and their possible role in autism spectrum disorder. Environ Res 166:234–250

    Article  Google Scholar 

  • Blaurock-Busch E, Amin OR, Rabah T (2011) Heavy metals and trace elements in hair and urine of a sample of Arab children with autistic spectrum disorder. Maedica 6:247

    Google Scholar 

  • Bölte S, Girdler S, Marschik PB (2019) The contribution of environmental exposure to the etiology of autism spectrum disorder. Cell Mol Life Sci 76:1275–1297

    Article  Google Scholar 

  • Calabrese V, Giordano J, Ruggieri M, Berritta D, Trovato A, Ontario M, Bianchini R, Calabrese E (2016) Hormesis, cellular stress response, and redox homeostasis in autism spectrum disorders. J Neurosci Res 94:1488–1498

    Article  CAS  Google Scholar 

  • Crăciun EC, Bjørklund G, Tinkov AA, Urbina MA, Skalny AV, Rad F, Dronca E (2016) Evaluation of whole blood zinc and copper levels in children with autism spectrum disorder. Metab Brain Dis 31:887–890

    Article  Google Scholar 

  • Dickerson AS, Rahbar MH, Bakian AV, Bilder DA, Harrington RA, Pettygrove S, Kirby RS, Durkin MS, Han I, Moyé LA (2016) Autism spectrum disorder prevalence and associations with air concentrations of lead, mercury, and arsenic. Environ Monitoring assessment 188:1–15

    Article  CAS  Google Scholar 

  • El-Ansary A, Bjørklund G, Tinkov AA, Skalny AV, Al Dera H (2017) Relationship between selenium, lead, and mercury in red blood cells of Saudi autistic children. Metab Brain Dis 32:1073–1080

    Article  CAS  Google Scholar 

  • Eqani SAMAS, Khuram F, Alamdar A, Tahir A, Shah STA, Nasir A, Javed S, Bibi N, Hussain A, Rasheed H (2020) Environmental exposure pathway analysis of trace elements and autism risk in Pakistani children population. Sci Total Environ 712:136471

    Article  Google Scholar 

  • Fiłon J, Ustymowicz-Farbiszewska J, Krajewska-Kułak E (2020) Analysis of lead, arsenic and calcium content in the hair of children with autism spectrum disorder. BMC Public Health 20:1–8

    Article  Google Scholar 

  • Fuentes-Albero M, Puig-Alcaraz C, Cauli O (2015) Lead excretion in Spanish children with autism spectrum disorder. Brain Sci 5:58–68

    Article  CAS  Google Scholar 

  • Imbriani G, Panico A, Grassi T, Idolo A, Serio F, Bagordo F, De Filippis G, De Giorgi D, Antonucci G, Piscitelli P (2021) Early-life exposure to environmental air pollution and autism spectrum disorder: a review of available evidence. Int J Environ Res Public Health 18:1204

    Article  CAS  Google Scholar 

  • Jan AT, Azam M, Siddiqui K, Ali A, Choi I, Haq QM (2015) Heavy metals and human health: mechanistic insight into toxicity and counter defense system of antioxidants. Int J Mol Sci 16:29592–29630

    Article  CAS  Google Scholar 

  • Kloke JD, McKean JW (2012) Rfit: rank-based estimation for linear models. R J 4:57

    Article  Google Scholar 

  • Li S-o, Wang J-l, Bjørklund G, Zhao W-n, Yin C-h (2014) Serum copper and zinc levels in individuals with autism spectrum disorders. Neuroreport 25:1216–1220

    Article  CAS  Google Scholar 

  • Meguid NA, Anwar M, Bjørklund G, Hashish A, Chirumbolo S, Hemimi M, Sultan E (2017) Dietary adequacy of Egyptian children with autism spectrum disorder compared to healthy developing children. Metab Brain Disease 32:607–615

    Article  Google Scholar 

  • Mohammadi MR, Ahmadi N, Khaleghi A, Zarafshan H, Mostafavi S-A, Kamali K, Rahgozar M, Ahmadi A, Hooshyari Z, Alavi SS (2019) Prevalence of autism and its comorbidities and the relationship with maternal psychopathology: a national population-based study. Arch Iranian Med 22:546–553

    Google Scholar 

  • Mostafa GA, Bjørklund G, Urbina MA, Al-Ayadhi LY (2016) The positive association between elevated blood lead levels and brain-specific autoantibodies in autistic children from low lead-polluted areas. Metab Brain Disease 31:1047–1054

    Article  CAS  Google Scholar 

  • Nevison CD (2014) A comparison of temporal trends in United States autism prevalence to trends in suspected environmental factors. Environ Health 13:1–16

    Article  CAS  Google Scholar 

  • Obrenovich ME, Shamberger RJ, Lonsdale D (2011) Altered heavy metals and transketolase found in autistic spectrum disorder. Biol Trace Element Res 144:475–486

    Article  CAS  Google Scholar 

  • Ousley O, Cermak T (2014) Autism spectrum disorder: defining dimensions and subgroups. Current Dev Disorders Reports 1:20–28

    Article  Google Scholar 

  • Priya MDL, Geetha A (2011) Level of trace elements (copper, zinc, magnesium and selenium) and toxic elements (lead and mercury) in the hair and nail of children with autism. Biol Trace Element Res 142:148–158

    Article  Google Scholar 

  • Rahbar MH, Samms-Vaughan M, Lee M, Zhang J, Hessabi M, Bressler J, Bach MA, Grove ML, Shakespeare-Pellington S, Beecher C (2020) Interaction between a mixture of heavy metals (lead, mercury, arsenic, cadmium, manganese, aluminum) and GSTP1, GSTT1, and GSTM1 in relation to autism spectrum disorder. Res Autism Spectrum Disorders 79:101681

    Article  Google Scholar 

  • Roberts AL, Lyall K, Hart JE, Laden F, Just AC, Bobb JF, Koenen KC, Ascherio A, Weisskopf MG (2013) Perinatal air pollutant exposures and autism spectrum disorder in the children of Nurses’ Health Study II participants. Environ Health Perspect 121:978–984

    Article  Google Scholar 

  • Saghazadeh A, Rezaei N (2017) 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 Neuro-Psychopharmacol Biol Psychiat 79:340–368

    Article  CAS  Google Scholar 

  • Santos JX, Rasga C, Vicente AM (2021) Exposure to xenobiotics and gene-environment interactions in autism spectrum disorder: a systematic review. . In: Michael F (Editor), Autism spectrum disorder: profile, heterogeneity, neurobiology and intervention. doi: https://doi.org/10.5772/intechopen.95758. BoD – Books on Demand, pp. 133

  • Skalny AV, Simashkova NV, Klyushnik TP, Grabeklis AR, Radysh IV, Skalnaya MG, Tinkov AA (2017) Analysis of hair trace elements in children with autism spectrum disorders and communication disorders. Biol Trace Element Res 177:215–223

    Article  CAS  Google Scholar 

  • Sulaiman R, Wang M, Ren X (2020) Exposure to aluminum, cadmium, and mercury and autism spectrum disorder in children: a systematic review and meta-analysis. Chem Res Toxicol 33:2699–2718

    Article  CAS  Google Scholar 

  • Vakilizadeh N, Abedi A, Mohseni Ezhiyeh A (2017) Investigating validity and reliability of early screening for autistic traits-Persian version (ESAT-PV) in toddlers. Arch Rehabilit 18:182–193

    Article  Google Scholar 

  • Weitlauf AS, McPheeters ML, Peters B, Sathe N, Travis R, Aiello R, Williamson E, Veenstra-VanderWeele J, Krishnaswami S, Jerome R (2014) Therapies for children with autism spectrum disorder: behavioral interventions update. AHRQ Comparative Effectiveness Reviews. No. 137. Rockville (MD): Agency for Healthcare Research and Quality (US); 2014 Aug. Report No: 14-EHC036-EF

  • Yao Y, Walsh WJ, McGinnis WR, Praticò D (2006) Altered vascular phenotype in autism: correlation with oxidative stress. Arch Neurol 63:1161–1164

  • Yasuda H, Yasuda Y, Tsutsui T (2013) Estimation of autistic children by metallomics analysis. Scientific Reports 3:1–8

    Google Scholar 

  • Yorbik Ö, Kurt İ, Haşimi A, Öztürk Ö (2010) Chromium, cadmium, and lead levels in urine of children with autism and typically developing controls. Biol Trace Element Res 135:10–15

    Article  CAS  Google Scholar 

  • Yorbik O, Sayal A, Akay C et al (2002) Investigation of antioxidant enzymes in children with autistic disorder. Prostaglandins Leukot Essent Fatty Acids 67(5):341–343

Download references

Acknowledgements

We would like to acknowledge the assistance of the Medical Toxicology and Drug Abuse Research Center (MTDRC) and also Clinical Research Development Unit of Imam Reza Hospital at the Birjand University of Medical Sciences. Special thanks to Dr. Lukasz J. Binkowski and Dr. Martyna Błaszczyk for their assistance in improving the manuscript. In addition, our sincere appreciation goes to all patients who participated in this study.

Availability of data and materials

The datasets used and/or analyzed during the current research are available from the corresponding author on request.

Funding

This study was supported by the Birjand University of Medical Sciences (Grant number: 1398.4868).

Author information

Authors and Affiliations

  1. Medical Toxicology and Drug Abuse Research Center (MTDRC), Birjand University of Medical Sciences, Birjand, Iran

    Maryam Rezaei, Azam Rezaei & Samaneh Nakhaee

  2. Psychiatry and Behavioral Science Research Center, Birjand University of Medical Sciences, Birjand, Iran

    Aliakbar Esmaeili

  3. Biostatistics Department, School of Public Health, Iran University of Medical Sciences, Tehran, Iran

    Nemam Ali Azadi

  4. Substance Abuse Prevention Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran

    Borhan Mansouri

Authors
  1. Maryam Rezaei
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Azam Rezaei
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Aliakbar Esmaeili
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Samaneh Nakhaee
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Nemam Ali Azadi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Borhan Mansouri
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

MR and BM were the overall coordinators. MR, AR, AE, SN, NA, and BM contributed to the design of the study, interpretation of the results, and drafting of the manuscript. MR and AR conducted the data collection. NA did data analysis. All authors have read and approved the final version of the manuscript.

Corresponding author

Correspondence to Borhan Mansouri.

Ethics declarations

Ethics approval and consent to participate

This study was approved by the research and ethics committee of Birjand University of Medical Sciences (no. IR.BUMS.REC.1397.204).

Consent for publication

Not applicable

Competing interests

The authors declare no competing interests.

Additional information

Responsible editor: Lotfi Aleya

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Rezaei, M., Rezaei, A., Esmaeili, A. et al. A case–control study on the relationship between urine trace element levels and autism spectrum disorder among Iranian children. Environ Sci Pollut Res 29, 57287–57295 (2022). https://doi.org/10.1007/s11356-022-19933-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11356-022-19933-1

Keywords

Search

Navigation