Archives of Toxicology

, Volume 91, Issue 11, pp 3459–3467 | Cite as

Early life arsenic exposure, infant and child growth, and morbidity: a systematic review

  • Anisur RahmanEmail author
  • Caroline Granberg
  • Lars-Åke Persson
Review Article


Epidemiological studies have suggested a negative association between early life arsenic exposure and fetal size at birth, and subsequently with child morbidity and growth. However, our understanding of the relationship between arsenic exposure and morbidity and growth is limited. This paper aims to systematically review original human studies with an analytical epidemiological study design that have assessed arsenic exposure in fetal life or early childhood and evaluated the association with one or several of the following outcomes: fetal growth, birth weight or other birth anthropometry, infant and child growth, infectious disease morbidity in infancy and early childhood. A literature search was conducted in PubMed, TOXLINE, Web of Science, SciFinder and Scopus databases filtered for human studies. Based on the predefined eligibility criteria, two authors independently evaluated the studies. A total of 707 studies with morbidity outcomes were identified, of which six studies were eligible and included in this review. For the growth outcomes, a total of 2959 studies were found and nine fulfilled the criteria and were included in the review. A majority of the papers (10/15) emanated from Bangladesh, three from the USA, one from Romania and one from Canada. All included studies on arsenic exposure and morbidity showed an increased risk of respiratory tract infections and diarrhea. The findings in the studies of arsenic exposure and fetal, infant, and child growth were heterogeneous. Arsenic exposure was not associated with fetal growth. There was limited evidence of negative associations between arsenic exposures and birth weight and growth during early childhood. More studies from arsenic-affected low- and middle-income countries are needed to support the generalizability of study findings.


Arsenic Human studies Growth Morbidity Systematic review 


  1. Ahmed S, Mahabbat-e Khoda S, Rekha RS et al (2011) Arsenic-associated oxidative stress, inflammation, and immune disruption in human placenta and cord blood. Environ Health Perspect 119(2):258–264. doi: 10.1289/ehp.1002086 CrossRefPubMedGoogle Scholar
  2. Bloom MS, Neamtiu IA, Surdu S et al (2016) Low level arsenic contaminated water consumption and birth outcomes in Romania—An exploratory study. Reprod Toxicol 59:8–16. doi: 10.1016/j.reprotox.2015.10.012 CrossRefPubMedGoogle Scholar
  3. Conde P, Acosta-Saavedra LC, Goytia-Acevedo RC, Calderon-Aranda ES (2007) Sodium arsenite-induced inhibition of cell proliferation is related to inhibition of IL-2 mRNA expression in mouse activated T cells. Arch Toxicol 81(4):251–259. doi: 10.1007/s00204-006-0152-7 CrossRefPubMedGoogle Scholar
  4. Farzan SF, Korrick S, Li Z et al (2013) In utero arsenic exposure and infant infection in a United States cohort: a prospective study. Environ Res 126:24–30. doi: 10.1016/j.envres.2013.05.001 CrossRefPubMedGoogle Scholar
  5. Farzan SF, Li Z, Korrick SA et al (2016) Infant infections and respiratory symptoms in relation to in utero arsenic exposure in a US cohort. Environ Health Perspect 124(6):840–847. doi: 10.1289/ehp.1409282 PubMedGoogle Scholar
  6. Gardner RM, Kippler M, Tofail F et al (2013) Environmental exposure to metals and children’s growth to age 5 years: a prospective cohort study. Am J Epidemiol 177(12):1356–1367. doi: 10.1093/aje/kws437 CrossRefPubMedPubMedCentralGoogle Scholar
  7. George CM, Brooks WA, Graziano JH et al (2015) Arsenic exposure is associated with pediatric pneumonia in rural Bangladesh: a case control study. Environ Health 14:83. doi: 10.1186/s12940-015-0069-9 CrossRefPubMedPubMedCentralGoogle Scholar
  8. Gilbert-Diamond D, Emond JA, Baker ER, Korrick SA, Karagas MR (2016) Relation between in utero arsenic exposure and birth outcomes in a cohort of mothers and their newborns from New Hampshire. Environ Health Perspect 124(8):1299–1307. doi: 10.1289/ehp.1510065 CrossRefPubMedPubMedCentralGoogle Scholar
  9. Heck JE, Chen Y, Grann VR, Slavkovich V, Parvez F, Ahsan H (2008) Arsenic exposure and anemia in Bangladesh: a population-based study. J Occup Environ Med 50(1):80–87. doi: 10.1097/JOM.0b013e31815ae9d4 CrossRefPubMedGoogle Scholar
  10. Huyck KL, Kile ML, Mahiuddin G et al (2007) Maternal arsenic exposure associated with low birth weight in Bangladesh. J Occup Environ Med 49(10):1097–1104. doi: 10.1097/JOM.0b013e3181566ba0 CrossRefPubMedGoogle Scholar
  11. International Agency for Research on Cancer (IARC) (2004) Some drinking-water disinfectants and contaminants, including arsenic. IARC Monogr Eval Carcinog Risks Hum 84:1–477Google Scholar
  12. Kile ML, Cardenas A, Rodrigues E et al (2016) Estimating effects of arsenic exposure during pregnancy on perinatal outcomes in a Bangladeshi cohort. Epidemiology 27(2):173–181. doi: 10.1097/EDE.0000000000000416 PubMedPubMedCentralGoogle Scholar
  13. Kippler M, Wagatsuma Y, Rahman A et al (2012) Environmental exposure to arsenic and cadmium during pregnancy and fetal size: a longitudinal study in rural Bangladesh. Reprod Toxicol 34(4):504–511. doi: 10.1016/j.reprotox.2012.08.002 CrossRefPubMedGoogle Scholar
  14. Liu L, Oza S, Hogan D et al (2015) Global, regional, and national causes of child mortality in 2000–13, with projections to inform post-2015 priorities: an updated systematic analysis. Lancet 385(9966):430–440. doi: 10.1016/S0140-6736(14)61698-6 CrossRefPubMedGoogle Scholar
  15. Lo CK, Mertz D, Loeb M (2014) Newcastle-Ottawa Scale: comparing reviewers’ to authors’ assessments. BMC Med Res Methodol 14:45. doi: 10.1186/1471-2288-14-45 CrossRefPubMedPubMedCentralGoogle Scholar
  16. Milton AH, Rahman M (2002) Respiratory effects and arsenic contaminated well water in Bangladesh. Int J Environ Health Res 12(2):175–179. doi: 10.1080/09603120220129346 CrossRefPubMedGoogle Scholar
  17. Milton AH, Smith W, Rahman B et al (2005) Chronic arsenic exposure and adverse pregnancy outcomes in bangladesh. Epidemiology 16(1):82–86CrossRefPubMedGoogle Scholar
  18. Moon KA, Guallar E, Umans JG et al (2013) Association between exposure to low to moderate arsenic levels and incident cardiovascular disease. A prospective cohort study. Ann Intern Med 159(10):649–659. doi: 10.7326/0003-4819-159-10-201311190-00719 PubMedPubMedCentralGoogle Scholar
  19. Mridha MK, Matias SL, Chaparro CM et al (2016) Lipid-based nutrient supplements for pregnant women reduce newborn stunting in a cluster-randomized controlled effectiveness trial in Bangladesh. Am J Clin Nutr 103(1):236–249. doi: 10.3945/ajcn.115.111336 CrossRefPubMedGoogle Scholar
  20. Mukherjee A, Sengupta MK, Hossain MA et al (2006) Arsenic contamination in groundwater: a global perspective with emphasis on the Asian scenario. J Health Popul Nutr 24(2):142–163PubMedGoogle Scholar
  21. Navas-Acien A, Silbergeld EK, Pastor-Barriuso R, Guallar E (2008) Arsenic exposure and prevalence of type 2 diabetes in US adults. JAMA 300(7):814–822. doi: 10.1001/jama.300.7.814 CrossRefPubMedGoogle Scholar
  22. Ng JC, Wang J, Shraim A (2003) A global health problem caused by arsenic from natural sources. Chemosphere 52(9):1353–1359. doi: 10.1016/S0045-6535(03)00470-3 CrossRefPubMedGoogle Scholar
  23. NIPORT (2014) Bangladesh Demographic and Health Survey 2014: National Institute of Population Research and Training, Mitra and Associates, and Macro International. Dhaka, Bangladesh and Calverton, MarylandGoogle Scholar
  24. Persson LA, Arifeen S, Ekstrom EC et al (2012) Effects of prenatal micronutrient and early food supplementation on maternal hemoglobin, birth weight, and infant mortality among children in Bangladesh: the MINIMat randomized trial. JAMA 307(19):2050–2059. doi: 10.1001/jama.2012.4061 CrossRefPubMedGoogle Scholar
  25. Quansah R, Armah FA, Essumang DK et al (2015) Association of arsenic with adverse pregnancy outcomes/infant mortality: a systematic review and meta-analysis. Environ Health Perspect 123(5):412–421. doi: 10.1289/ehp.1307894 PubMedPubMedCentralGoogle Scholar
  26. Rahman M, Tondel M, Chowdhury IA, Axelson O (1999a) Relations between exposure to arsenic, skin lesions, and glucosuria. Occup Environ Med 56(4):277–281CrossRefPubMedPubMedCentralGoogle Scholar
  27. Rahman M, Tondel M, Ahmad SA, Chowdhury IA, Faruquee MH, Axelson O (1999b) Hypertension and arsenic exposure in Bangladesh. Hypertension 33(1):74–78CrossRefPubMedGoogle Scholar
  28. Rahman A, Vahter M, Ekstrom EC et al (2007) Association of arsenic exposure during pregnancy with fetal loss and infant death: a cohort study in Bangladesh. Am J Epidemiol 165(12):1389–1396. doi: 10.1093/aje/kwm025 (pii:kwm025) CrossRefPubMedGoogle Scholar
  29. Rahman A, Vahter M, Smith AH et al (2009) Arsenic exposure during pregnancy and size at birth: a prospective cohort study in Bangladesh. Am J Epidemiol 169(3):304–312. doi: 10.1093/aje/kwn332 (pii:kwn332) CrossRefPubMedGoogle Scholar
  30. Rahman A, Vahter M, Ekstrom EC, Persson LA (2011) Arsenic exposure in pregnancy increases the risk of lower respiratory tract infection and diarrhea during infancy in Bangladesh. Environ Health Perspect 119(5):719–724. doi: 10.1289/ehp.1002265 CrossRefPubMedGoogle Scholar
  31. Raqib R, Ahmed S, Sultana R et al (2009) Effects of in utero arsenic exposure on child immunity and morbidity in rural Bangladesh. Toxicol Lett 185(3):197–202 (pii:S0378-4274(09)00018-6) CrossRefPubMedGoogle Scholar
  32. Saha KK, Engstrom A, Hamadani JD, Tofail F, Rasmussen KM, Vahter M (2012) Pre- and postnatal arsenic exposure and body size to 2 years of age: a cohort study in rural Bangladesh. Environ Health Perspect 120(8):1208–1214. doi: 10.1289/ehp.1003378 CrossRefPubMedPubMedCentralGoogle Scholar
  33. Sazawal S, Dhingra U, Dhingra P et al (2010) Micronutrient fortified milk improves iron status, anemia and growth among children 1–4 years: a double masked, randomized, controlled trial. PLoS One 5(8):e12167. doi: 10.1371/journal.pone.0012167 CrossRefPubMedPubMedCentralGoogle Scholar
  34. Selgrade MK (2007) Immunotoxicity: the risk is real. Toxicol Sci 100(2):328–332. doi: 10.1093/toxsci/kfm244 CrossRefPubMedGoogle Scholar
  35. Smith AH, Lingas EO, Rahman M (2000) Contamination of drinking-water by arsenic in Bangladesh: a public health emergency. Bull World Health Organ 78(9):1093–1103PubMedPubMedCentralGoogle Scholar
  36. Smith AH, Yunus M, Khan AF et al (2013) Chronic respiratory symptoms in children following in utero and early life exposure to arsenic in drinking water in Bangladesh. Int J Epidemiol 42(4):1077–1086. doi: 10.1093/ije/dyt120 CrossRefPubMedPubMedCentralGoogle Scholar
  37. Svefors P, Rahman A, Ekstrom EC et al (2016) Stunted at 10 Years. Linear growth trajectories and stunting from birth to pre-adolescence in a rural Bangladeshi cohort. PLoS One 11(3):e0149700. doi: 10.1371/journal.pone.0149700 CrossRefPubMedPubMedCentralGoogle Scholar
  38. Thomas S, Arbuckle TE, Fisher M, Fraser WD, Ettinger A, King W (2015) Metals exposure and risk of small-for-gestational age birth in a Canadian birth cohort: the MIREC study. Environ Res 140:430–439. doi: 10.1016/j.envres.2015.04.018 CrossRefPubMedGoogle Scholar
  39. Tondel M, Rahman M, Magnuson A, Chowdhury IA, Faruquee MH, Ahmad SA (1999) The relationship of arsenic levels in drinking water and the prevalence rate of skin lesions in Bangladesh. Environ Health Perspect 107(9):727–729CrossRefPubMedPubMedCentralGoogle Scholar
  40. UNICEF (2015). Levels & trends in child mortality 2015. (Available from Accessed 30 June 2017
  41. Vahter ME (2007) Interactions between arsenic-induced toxicity and nutrition in early life. J Nutr 137(12):2798–2804PubMedGoogle Scholar
  42. Vahter M (2009) Effects of arsenic on maternal and fetal health. Annu Rev Nutr 29:381–399. doi: 10.1146/annurev-nutr-080508-141102 CrossRefPubMedGoogle Scholar
  43. von Ehrenstein OS, Guha Mazumder DN, Hira-Smith M et al (2006) Pregnancy outcomes, infant mortality, and arsenic in drinking water in West Bengal, India. Am J Epidemiol 163(7):662–669. doi: 10.1093/aje/kwj089 CrossRefGoogle Scholar
  44. Wells GA, Shea B, O’Connell D et al (2013) The Newcastle–Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. (Available from Accessed 30 June 2017

Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  1. 1.Maternal and Child Health DivisionInternational Centre for Diarrhoeal Disease Research, Bangladesh (icddr, b)DhakaBangladesh
  2. 2.Department of Women’s and Children’s Health, International Maternal and Child Health (IMCH)Uppsala UniversityUppsalaSweden
  3. 3.Department of Disease Control, Faculty of Infectious and Tropical DiseasesLondon School of Hygiene and Tropical MedicineLondonUK

Personalised recommendations