Environmental Science and Pollution Research

, Volume 26, Issue 18, pp 17875–17884 | Cite as

Low blood lead levels and attention-deficit hyperactivity disorder in children: a systematic review and meta-analysis

  • Jianjun He
  • Huacheng Ning
  • Ruixue HuangEmail author
Environmental Pollution and Energy Management


Attention-deficit hyperactivity disorder (ADHD) of children is one of the most common neurodevelopmental diseases; the etiology remains unclear. We reviewed and meta-analyzed case-control studies to assess the effects of blood lead levels in children on ADHD symptoms. Relevant studies were identified by searching electronic databases. A meta-analysis was performed using the fixed model of Review Manager 5.3 software. Seven relevant studies were identified. The case groups exhibited significant increases in ADHD symptoms [mean difference (MD), 0.59; 95% confidence interval (CI), 0.50–0.68; p < 0.0001]. Subgroup assessment showed that even children with blood lead levels <3 μg/dL exhibited significant increases in ADHD symptoms (MD, 0.47; 95% CI, 0.39–0.56; p < 0.0001). Subgroup assessment also showed that children aged 5–12 years exhibited more significant increases in ADHD symptoms (MD, 1.35; 95% CI, 0.28–2.41; p < 0.0001) than children aged >12 years. Our findings suggest that low blood lead levels may be associated with ADHD symptoms in children. However, caution is needed when interpreting the results because among-study heterogeneity was in play. Primary interventions should focus on children with low blood lead levels.


ADHD Children Lead Systematic review Meta-analysis Blood level 


Author’s contribution

Ruixue Huang conceived and designed the study. Ruixue Huang, Huacheng Ning performed eligibility screening and data extraction. Jianjun He analyzed the data and performed the statistical analysis. Ruixue Huang and Jianjun He wrote the initial manuscript. Ruixue Huang critically revised the manuscript and polish the English language.

Compliance with ethical standards

Conflicts of interest

The authors declare that they have no conflicts of interest.

Supplementary material

11356_2017_9799_MOESM1_ESM.doc (64 kb)
ESM 1 (DOC 64 kb)


  1. Arbuckle TE, Davis K, Boylan K, Fisher M, Fu J (2016) Bisphenol A, phthalates and lead and learning and behavioral problems in Canadian children 6-11 years of age: CHMS 2007-2009. Neurotoxicology 54:89–98Google Scholar
  2. Bakare MO (2012) Attention deficit hyperactivity symptoms and disorder (ADHD) among African children: a review of epidemiology and co-morbidities. Afr J Psychiatry (Johannesbg) 15:358–361Google Scholar
  3. Bellinger DC (2008) Very low lead exposure and children’s neurodevelopment. Curr Opin Pediatr 20:172–177CrossRefGoogle Scholar
  4. Bonfill X, Centro Cochrane I (2014) The Cochrane Collaboration turns 20. Med Clin (Barc) 143:210–215CrossRefGoogle Scholar
  5. Braun JM, Kahn RS, Froehlich T, Auinger P, Lanphear BP (2006) Exposures to environmental toxicants and attention deficit hyperactivity disorder in US children. Environ Health Perspect 114(12):1904–1909Google Scholar
  6. Centers for Disease C, Prevention (2010) Increasing prevalence of parent-reported attention-deficit/hyperactivity disorder among children—United States, 2003 and 2007. MMWR Morb Mortal Wkly Rep 59:1439–1443Google Scholar
  7. Cho SC, Kim BN, Hong YC, Shin MS, Yoo HJ, Kim JW, Bhang SY, Cho IH, Kim HW (2010) Effect of environmental exposure to lead and tobacco smoke on inattentive and hyperactive symptoms and neurocognitive performance in children. J Child Psychol Psychiatry 51:1050–1057CrossRefGoogle Scholar
  8. Ciesielski T, Weuve J, Bellinger DC, Schwartz J, Lanphear B, Wright RO (2012) Cadmium exposure and neurodevelopmental outcomes in U.S. children. Environ Health Perspect 120:758–763CrossRefGoogle Scholar
  9. Cortese S (2010) Review: ADHD impairs quality of life, but children and young people with ADHD perceive less impairment than parents. Evid Based Ment Health 13:76CrossRefGoogle Scholar
  10. Council On Environmental H (2016) Prevention of childhood lead toxicity. Pediatrics 138Google Scholar
  11. Faraone SV, Asherson P, Banaschewski T, Biederman J, Buitelaar JK, Ramos-Quiroga JA, Rohde LA, Sonuga-Barke EJ, Tannock R, Franke B (2015) Attention-deficit/hyperactivity disorder. Nat Rev Dis Primers 1:15020CrossRefGoogle Scholar
  12. Forns J, Fort M, Casas M, Cáceres A, Guxens M, Gascon M, Garcia-Esteban R, Julvez J, Grimalt JO, Sunyer J (2014) Exposure to metals during pregnancy and neuropsychological development at the age of 4 years. NeuroToxicology 40:16–22Google Scholar
  13. Froehlich TE, Lanphear BP, Auinger P, Hornung R, Epstein JN, Braun J, Kahn RS (2009) Association of tobacco and lead exposures with attention-deficit/hyperactivity disorder. Pediatrics 124(6):e1054–63Google Scholar
  14. Goodlad JK, Marcus DK, Fulton JJ (2013) Lead and attention-deficit/hyperactivity disorder (ADHD) symptoms: a meta-analysis. Clin Psychol Rev 33:417–425CrossRefGoogle Scholar
  15. Ha M, Kwon HJ, Lim MH, Jee YK, Hong YC, Leem JH, Sakong J, Bae JM, Hong SJ, Roh YM, Jo SJ (2009) Low blood levels of lead and mercury and symptoms of attention deficit hyperactivity in children: a report of the children’s health and environment research (CHEER). Neurotoxicology 30:31–36CrossRefGoogle Scholar
  16. Huang R, Wang K, Hu J (2016) Effect of probiotics on depression: a systematic review and meta-analysis of randomized controlled trials nutrients 8(8). doi: 10.3390/nu8080483
  17. Hubbs-Tait L, Nation JR, Krebs NF, Bellinger DC (2005) Neurotoxicants, micronutrients, and social environments: individual and combined effects on Children's development. Psychol Sci Public Interest 6:57–121CrossRefGoogle Scholar
  18. Joo H, Lim MH, Ha M, Kwon HJ, Yoo SJ, Choi KH, Paik KC (2017) Secondhand smoke exposure and low blood lead levels in association with attention-deficit hyperactivity disorder and its symptom domain in children: a community-based case-control study. Nicotine Tob Res 19:94–101CrossRefGoogle Scholar
  19. Kerekes N, Brandstrom S, Lundstrom S, Rastam M, Nilsson T, Anckarsater H (2013) ADHD, autism spectrum disorder, temperament, and character: phenotypical associations and etiology in a Swedish childhood twin study. Compr Psychiatry 54:1140–1147CrossRefGoogle Scholar
  20. Kim S, Arora M, Fernandez C, Landero J, Caruso J, Chen A (2013) Lead, mercury, and cadmium exposure and attention deficit hyperactivity disorder in children. Environ Res 126:105–110CrossRefGoogle Scholar
  21. Kim Y, Cho SC, Kim BN, Hong YC, Shin MS, Yoo HJ, Kim JW, Bhang SY (2010) Association between blood lead levels (<5 mug/dL) and inattention-hyperactivity and neurocognitive profiles in school-aged Korean children. Sci Total Environ 408:5737–5743CrossRefGoogle Scholar
  22. Mahboube FMTR, Seyyed M (2016) The study of serum lead level in children with ADHD referring to psychiatric clinic of Baharan Hospital, Zahedan, Southeastern Iran. Int J School Health 3:e28040Google Scholar
  23. Mitra AK, Ahua E, Saha PK (2012) Prevalence of and risk factors for lead poisoning in young children in Bangladesh. J Health Popul Nutr 30:404–409Google Scholar
  24. Needleman HL (2004) Low level lead exposure and the development of children. Southeast Asian J Trop Med Public Health 35:252–254Google Scholar
  25. Neugebauer J, Wittsiepe J, Kasper-Sonnenberg M, Schöneck N, Schölmerich A, Wilhelm M (2015) The influence of low level pre- and perinatal exposure to PCDD/Fs, PCBs, and lead on attention performance and attention-related behavior among German school-aged children: results from the Duisburg birth cohort study. Int J Hyg Environ Health 218(1):153–162Google Scholar
  26. Nigg JT, Knottnerus GM, Martel MM, Nikolas M, Cavanagh K, Karmaus W, Rappley MD (2008) Low blood lead levels associated with clinically diagnosed attention-deficit/hyperactivity disorder and mediated by weak cognitive control. Biol Psychiatry 63:325–331CrossRefGoogle Scholar
  27. Nigg JT, Nikolas M, Mark Knottnerus G, Cavanagh K, Friderici K (2010) Confirmation and extension of association of blood lead with attention-deficit/hyperactivity disorder (ADHD) and ADHD symptom domains at population-typical exposure levels. J Child Psychol Psychiatry 51:58–65CrossRefGoogle Scholar
  28. Nigg JT, Elmore AL, Natarajan N, Friderici KH, Nikolas MA (2016) Variation in an iron metabolism gene moderates the association between blood lead levels and attention-deficit/hyperactivity disorder in children. Psychol Sci 27:257–269CrossRefGoogle Scholar
  29. Park JH, Seo JH, Hong YS, Kim YM, Kang JW, Yoo JH, Chueh HW, Lee JH, Kwak MJ, Kim J, Woo HD, Kim DW, Bang YR, Choe BM (2016) Blood lead concentrations and attention deficit hyperactivity disorder in Korean children: a hospital-based case control study. BMC Pediatr 16:156CrossRefGoogle Scholar
  30. Patros CH, Alderson RM, Kasper LJ, Tarle SJ, Lea SE, Hudec KL (2016) Choice-impulsivity in children and adolescents with attention-deficit/hyperactivity disorder (ADHD): a meta-analytic review. Clin Psychol Rev 43:162–174CrossRefGoogle Scholar
  31. Polanczyk G, de Lima MS, Horta BL, Biederman J, Rohde LA (2007) The worldwide prevalence of ADHD: a systematic review and metaregression analysis. Am J Psychiatry 164:942–948CrossRefGoogle Scholar
  32. Polanczyk GV, Willcutt EG, Salum GA, Kieling C, Rohde LA (2014) ADHD prevalence estimates across three decades: an updated systematic review and meta-regression analysis. Int J Epidemiol 43:434–442CrossRefGoogle Scholar
  33. Schlack R, Holling H, Kurth BM, Huss M (2007) The prevalence of attention-deficit/hyperactivity disorder (ADHD) among children and adolescents in Germany. Initial results from the German Health Interview and Examination Survey for Children and Adolescents (KiGGS). Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 50:827–835CrossRefGoogle Scholar
  34. Sharma A, Couture J (2014) A review of the pathophysiology, etiology, and treatment of attention-deficit hyperactivity disorder (ADHD). Ann Pharmacother 48:209–225CrossRefGoogle Scholar
  35. Sioen I, Den Hond E, Nelen V, Van de Mieroop E, Croes K, Van Larebeke N, Nawrot TS, Schoeters G (2013) Prenatal exposure to environmental contaminants and behavioural problems at age 7-8years. Environ Int 59:225–231Google Scholar
  36. Solon O, Riddell TJ, Quimbo SA, Butrick E, Aylward GP, Lou Bacate M, Peabody JW (2008) Associations between cognitive function, blood lead concentration, and nutrition among children in the central Philippines. J Pediatr 152:237–243CrossRefGoogle Scholar
  37. Thapar A, Cooper M (2016) Attention deficit hyperactivity disorder. Lancet 387:1240–1250Google Scholar
  38. Thurston DL, Middelkamp JN, Mason E (1955) The late effects of lead poisoning. J Pediatr 47:413–423CrossRefGoogle Scholar
  39. Wang HL, Chen XT, Yang B, Ma FL, Wang S, Tang ML, Hao MG, Ruan DY (2008) Case-control study of blood lead levels and attention deficit hyperactivity disorder in Chinese children. Environ Health Perspect 116:1401–1406CrossRefGoogle Scholar
  40. Willcutt EG, Nigg JT, Pennington BF, Solanto MV, Rohde LA, Tannock R, Loo SK, Carlson CL, McBurnett K, Lahey BB (2012) Validity of DSM-IV attention deficit/hyperactivity disorder symptom dimensions and subtypes. J Abnorm Psychol 121:991–1010CrossRefGoogle Scholar
  41. Yoshimasu K, Kiyohara C, Takemura S, Nakai K (2014) A meta-analysis of the evidence on the impact of prenatal and early infancy exposures to mercury on autism and attention deficit/hyperactivity disorder in the childhood. Neurotoxicology 44:121–131CrossRefGoogle Scholar
  42. Zhang R, Huo X, Ho G, Chen X, Wang H, Wang T, Ma (2015) Attention-deficit/hyperactivity symptoms in preschool children from an E-waste recycling town: assessment by the parent report derived from DSM-IV. BMC Pediatrics 15(1). doi: 10.1186/s12887-015-0368-x

Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  1. 1.Changsha Medical UniversityChangshaChina
  2. 2.Department of Occupational and Environmental Health, Xiangya School of Public HealthCentral South UniversityChangshaChina

Personalised recommendations