Vol. 120, No. 6 CorrespondenceOpen AccessNeurotoxic Metal Coexposures and Neurodevelopmentis accompanied byAssociations of Early Childhood Manganese and Lead Coexposure with Neurodevelopment José G. Dórea José G. Dórea Search for more papers by this author Published:1 June 2012https://doi.org/10.1289/ehp.1205004Cited by:2AboutSectionsPDF ToolsDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InReddit Claus Henn et al. (2012) addressed a “real world scenario” of exposure to multiple neurotoxic metals in their unique and interesting study. They investigated manganese–lead coexposure and its association with neurodevelopmental deficiencies in Mexican children. Their rationale was that neurodevelopmental deficiencies of both metals together could be more severe than expected based on effects of exposure to each metal alone. Indeed, they observed a synergism between manganese and lead. Given the early age of the subjects (12 and 24 months of age), I suggest that some confounders not included in their model deserve consideration in regard to this study.Claus Henn et al. (2012) collected information on duration of breast-feeding, but it seems that in their statistical analyses, they adjusted only for sex, gestational age, hemoglobin, maternal IQ (intelligence quotient), and maternal education. Other confounders, such as thimerosal (a compound containing ethylmercury that is used as a preservative in some vaccines) and breast-feeding, may influence neurodevelopment outcomes. In countries such as Mexico, children 12–24 months of age may be immunized with thimerosal-containing vaccines (TCVs) (WHO 2011). Because of opposite effects on the central nervous system, the combination of breast-feeding and ethylmercury may influence neurodevelopmental outcomes. Kramer et al. (2008) showed that children who were exclusively breast-fed had improved cognitive development. Indeed, Kostial et al. (1978) demonstrated that infant rats fed cow’s milk diets absorbed more lead and manganese, which are associated with a higher relative retention of mercury in the brain.Blood levels of lead and manganese are indicators of ongoing exposure; however, ethylmercury has a short half-life and thus is unlikely to be concurrently measured in blood (Dórea et al. 2011). Nevertheless we can ascertain exposure from vaccination cards (Dórea et al. 2012; Marques et al. 2009). Following participants in the National Immunization Program of Mexico, the amount of ethylmercury from routine immunizations against hepatitis B (three doses), DTP (diphtheria, tetanus, and pertussis, three doses), and influenza can be estimated from records on vaccination cards. Additionally, during pregnancy, Mexican mothers may receive tetanus toxoid (TT) vaccines and other products, such as anti-RhoD immune globulins (given to Rh-negative mothers) that may contain thimerosal (Marques et al. 2009). These sources of prenatal and postnatal ethylmercury exposure should be considered significant sources of an additional neurotoxic coexposure—organic mercury.Claus Henn et al. (2012) realized that information on the association of neurodevelopment and coexposure to multiple chemicals is limited; the scientific literature is even more scarce for the specific exposure to small amounts of ethylmercury derived from TCVs (Oken and Bellinger 2008), which are largely used in nonindustrialized countries. However, recent work has suggested that when studies with young children are properly adjusted for exposure to TCVs, subtle neurodevelopmental effects can be demonstrated (Dórea et al. 2012; Marques et al. 2009; Mrozek-Budzyn 2011a, 2011b). Therefore, the potential for interaction of ethylmercury, manganese, and lead provides an opportunity to expand our knowledge.Factors related to maternal neurotoxic exposure and neurodevelopment (e.g., breast-feeding) are significant in studies of children’s exposure to ethylmercury (Marques et al. 2009). The study design used by Claus Henn et al. (2012) could provide further information on this timely issue and also provide direction for future studies of contaminants and confounders that affect neurodevelopment.The author declares that he has no actual or potential competing financial interests.ReferencesClaus Henn B, Schnaas L, Ettinger AS, Schwartz J, Lamadrid-Figueroa H, Hernández-Avila Met al.. 2012. Associations of early childhood manganese and lead coexposure with neurodevelopment.Environ Health Perspect 120:126-13121885384. Link, Google ScholarDórea JG, Bezerra VL, Fajon V, Horvat M. 2011. Speciation of methyl- and ethyl-mercury in hair of breastfed infants acutely exposed to thimerosal-containing vaccines.Clin Chim Acta 412:1563-156621575620. Crossref, Medline, Google ScholarDórea JG, Marques RC, Isejima C. 2012. Neurodevelopment of Amazonian infants: antenatal and postnatal exposure to methyl- and ethylmercury.J Biomed Biotechnol2012: 132876; doi:.10.1155/2012/132876. Crossref, Google ScholarKostial K, Kello D, Jugo S, Rabar I, Maljkovi’c T.. 1978. Influence of age on metal metabolism and toxicity.Environ Health Perspect 25:81-86720306. Link, Google ScholarKramer MS, Aboud F, Mironova E, Vanilovich I, Platt RW, Matush Let al.. 2008. Breastfeeding and child cognitive development. New evidence from a large randomized trial.Arch Gen Psychiatry 65:578-58418458209. Crossref, Medline, Google ScholarMarques RC, Dórea JG, Bernardi JV, Bastos WR, Malm O. 2009. Prenatal and postnatal mercury exposure, breastfeeding and neurodevelopment during the first 5 years.Cogn Behav Neurol 22:134-14119506431. Crossref, Medline, Google ScholarMrozek-Budzyn D, Majewska1 R, Kieltyka A, Augustyniak M, Mroz E, Skarupa A2011a. The influence of neonatal exposure to thimerosal containing vaccines on infants development in the first years of life. [Abstract]Ped Res 70:338. Crossref, Google ScholarMrozek-Budzyn D, Majewska1 R, Kieltyka A, Augustyniak M, Mroz E, Skarupa A2011b. The influence of infant’s exposure to thimerosal containing vaccines on the development in the first three years of life. [Abstract]Ped Res 70:340. Crossref, Google ScholarOken E, Bellinger DC. 2008. Fish consumption, methylmercury and child neurodevelopment.Curr Opin Pediatr 20:178-18318332715. Crossref, Medline, Google ScholarWHOImmunization Profile – Mexico.2011. Available: http://apps.who.int/immunization_monitoring/en/globalsummary/countryprofileresult.cfm?C=mex [accessed 2 May 2012]. Google ScholarFiguresReferencesRelatedDetailsCited By Dórea J (2019) Environmental exposure to low-level lead (Pb) co-occurring with other neurotoxicants in early life and neurodevelopment of children., Environmental Research, 10.1016/j.envres.2019.108641, (108641), Online publication date: 1-Aug-2019. Willhite C, Karyakina N, Yokel R, Yenugadhati N, Wisniewski T, Arnold I, Momoli F and Krewski D (2014) Systematic review of potential health risks posed by pharmaceutical, occupational and consumer exposures to metallic and nanoscale aluminum, aluminum oxides, aluminum hydroxide and its soluble salts, Critical Reviews in Toxicology, 10.3109/10408444.2014.934439, 44:sup4, (1-80), Online publication date: 1-Oct-2014. Related articlesAssociations of Early Childhood Manganese and Lead Coexposure with Neurodevelopment1 September 2011Environmental Health Perspectives Vol. 120, No. 6 June 2012Metrics About Article Metrics Publication History Originally published1 June 2012Published in print1 June 2012 Financial disclosuresPDF download License information EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. All content is public domain unless otherwise noted. Note to readers with disabilities EHP strives to ensure that all journal content is accessible to all readers. However, some figures and Supplemental Material published in EHP articles may not conform to 508 standards due to the complexity of the information being presented. If you need assistance accessing journal content, please contact [email protected]. Our staff will work with you to assess and meet your accessibility needs within 3 working days.