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Chemical mixtures, maternal exposure and infant neurodevelopment: Did we miss positive (breastfeeding) and negative (mercury) confounders?
Neurotoxicology and Teratology 45 (2014) 93
Contents lists available at ScienceDirect
Neurotoxicology and Teratology journal homepage: www.elsevier.com/locate/neutera
Chemical mixtures, maternal exposure and infant neurodevelopment: Did we miss positive (breastfeeding) and negative (mercury) confounders? Keywords: Breastfeeding Neurodevelopment Mercury Thimerosal Ethylmercury
Multiple exposures to environmental toxic metals are routinely expected in most low-income countries, and yet the subject is not frequently studied. Therefore, environmental health scientists welcome the work of Parajuli et al. (2014), who accomplished the difficult task of studying the potential effects of Pb, As, and Zn on neurodevelopment in a group of Nepalese infants. This report illustrates some of the challenges of assessing public health in these countries and the environmental conditions into which some children are born. Nevertheless, it is pertinent to raise awareness regarding some key points related to important potential influences on BSID II outcomes that were not addressed in this study. Specifically, this study did not evaluate breastfeeding duration and Hg exposure as two factors likely to exert positive and negative influences on infant development, respectively. Although Parajuli et al. apparently collected data on breastfeeding (their Table 1) they did not use them in the statistical model. Not including a known confounder as important as the type of feeding deserves comment regarding the observed BSID II outcomes. Neural maturation is faster in breastfed babies, and exclusive breastfeeding may overcome some of the neurotoxic effects caused by exposure during pregnancy (Dórea, 2007). It is possible that increased breastfeeding could have beneficial effects counteracting lead exposure during pregnancy (Marques et al., 2014). In this case, if breastfeeding were more prevalent and prolonged in this Nepalese cohort than in the Saudi Arabian, American, and Chinese cohorts, this influence could help explain the discrepancy between the lack of deficits at 6 months reported here, and the continued deficits in BSID scores in those cohorts. However, the lower Pb burden in this sample and the smaller sample size in the study are also important factors in this case. Co-exposure to Hg is a likely negative influence not addressed in this study. Low-income countries, like Nepal, are likely to use Thimerosalcontaining vaccines (TCVs) during pregnancy and during the heavy immunization scheme of infancy. Therefore, it is likely that the tested infants were also exposed to ethylmercury (etHg). Early exposure to TCV most probably will not affect cord-blood Hg concentrations, but continues to be an issue throughout the world. Indeed, recent studies addressing multiple exposures that included TCV-etHg indicated its
http://dx.doi.org/10.1016/j.ntt.2014.06.006 0892-0362/© 2014 Elsevier Inc. All rights reserved.
influence on BSID II outcomes. For example, in the Krakow cohort study of chemical mixtures (properly referenced in the Jedrychowski studies), when etHg exposure was integrated, found a significant and negative association compounded by Pb (Majewska and Dórea, 2012; Mrozek-Budzyn et al., 2012). Likewise, in Korea, post hoc analysis of exposure to mixtures of environmental chemicals revealed a significant association between BSID II tests and TCV-etHg (Lee and Ha, 2012). Given these reports of the effects of TCV on infant development, information about the use of Thimerosal in Nepal should be included in further studies of infant development. In addition, the protective effect of breastfeeding should be tested to understand how it may influence combined exposures to Pb and Hg in different forms. Nevertheless, the research by Parajuli et al. remains an important contribution both in representing a rarely researched population of Nepalese children, and by helping to understand how a mixture of chemicals impacted pregnant mothers and affected child development. Transparency Document The Transparency Document associated with this article can be found, in the online version. References Dórea JG. Maternal smoking and infant feeding: breastfeeding is better and safer. Matern Child Health J 2007;11:287–91. Parajuli RP, Fujiwara T, Umezaki M, Furusawa H, Watanabe C. Home environment and prenatal exposure to lead, arsenic and zinc on the neurodevelopment of sixmonth-old infants living in Chitwan Valley, Nepal. Neurotoxicol Teratol 2014;41C: 89–95. Lee BE, Ha EH. Response to commentary “co-exposure and confounders during neurodevelopment: we need them in the bigger picture of secondhand smoke exposure during pregnancy”. Environ Res 2012;112:235. Majewska MD, Dórea JG. Krakow's children and cognitive function: can the study by Jedrychowski et al. show us the bigger picture? Eur J Pediatr 2012;171:405. [author reply 407]. Marques RC, Bernardi JV, Dórea JG, de Fatima R, Moreira M, Malm O. Perinatal multiple exposure to neurotoxic (lead, methylmercury, ethylmercury, and aluminum) substances and neurodevelopment at six and 24 months of age. Environ Pollut 2014; 187C:130–5. Mrozek-Budzyn D, Majewska R, Kieltyka A, Augustyniak M. Neonatal exposure to Thimerosal from vaccines and child development in the first 3 years of life. Neurotoxicol Teratol 2012;34:592–7.
José G. Dórea C.P. 04322, Faculty of Health Sciences, Universidade de Brasilia, 70919-970 Brasilia, DF, Brazil E-mail address: [email protected]. 1 March 2014
Contents lists available at ScienceDirect
Neurotoxicology and Teratology journal homepage: www.elsevier.com/locate/neutera
Chemical mixtures, maternal exposure and infant neurodevelopment: Did we miss positive (breastfeeding) and negative (mercury) confounders? Keywords: Breastfeeding Neurodevelopment Mercury Thimerosal Ethylmercury
Multiple exposures to environmental toxic metals are routinely expected in most low-income countries, and yet the subject is not frequently studied. Therefore, environmental health scientists welcome the work of Parajuli et al. (2014), who accomplished the difficult task of studying the potential effects of Pb, As, and Zn on neurodevelopment in a group of Nepalese infants. This report illustrates some of the challenges of assessing public health in these countries and the environmental conditions into which some children are born. Nevertheless, it is pertinent to raise awareness regarding some key points related to important potential influences on BSID II outcomes that were not addressed in this study. Specifically, this study did not evaluate breastfeeding duration and Hg exposure as two factors likely to exert positive and negative influences on infant development, respectively. Although Parajuli et al. apparently collected data on breastfeeding (their Table 1) they did not use them in the statistical model. Not including a known confounder as important as the type of feeding deserves comment regarding the observed BSID II outcomes. Neural maturation is faster in breastfed babies, and exclusive breastfeeding may overcome some of the neurotoxic effects caused by exposure during pregnancy (Dórea, 2007). It is possible that increased breastfeeding could have beneficial effects counteracting lead exposure during pregnancy (Marques et al., 2014). In this case, if breastfeeding were more prevalent and prolonged in this Nepalese cohort than in the Saudi Arabian, American, and Chinese cohorts, this influence could help explain the discrepancy between the lack of deficits at 6 months reported here, and the continued deficits in BSID scores in those cohorts. However, the lower Pb burden in this sample and the smaller sample size in the study are also important factors in this case. Co-exposure to Hg is a likely negative influence not addressed in this study. Low-income countries, like Nepal, are likely to use Thimerosalcontaining vaccines (TCVs) during pregnancy and during the heavy immunization scheme of infancy. Therefore, it is likely that the tested infants were also exposed to ethylmercury (etHg). Early exposure to TCV most probably will not affect cord-blood Hg concentrations, but continues to be an issue throughout the world. Indeed, recent studies addressing multiple exposures that included TCV-etHg indicated its
http://dx.doi.org/10.1016/j.ntt.2014.06.006 0892-0362/© 2014 Elsevier Inc. All rights reserved.
influence on BSID II outcomes. For example, in the Krakow cohort study of chemical mixtures (properly referenced in the Jedrychowski studies), when etHg exposure was integrated, found a significant and negative association compounded by Pb (Majewska and Dórea, 2012; Mrozek-Budzyn et al., 2012). Likewise, in Korea, post hoc analysis of exposure to mixtures of environmental chemicals revealed a significant association between BSID II tests and TCV-etHg (Lee and Ha, 2012). Given these reports of the effects of TCV on infant development, information about the use of Thimerosal in Nepal should be included in further studies of infant development. In addition, the protective effect of breastfeeding should be tested to understand how it may influence combined exposures to Pb and Hg in different forms. Nevertheless, the research by Parajuli et al. remains an important contribution both in representing a rarely researched population of Nepalese children, and by helping to understand how a mixture of chemicals impacted pregnant mothers and affected child development. Transparency Document The Transparency Document associated with this article can be found, in the online version. References Dórea JG. Maternal smoking and infant feeding: breastfeeding is better and safer. Matern Child Health J 2007;11:287–91. Parajuli RP, Fujiwara T, Umezaki M, Furusawa H, Watanabe C. Home environment and prenatal exposure to lead, arsenic and zinc on the neurodevelopment of sixmonth-old infants living in Chitwan Valley, Nepal. Neurotoxicol Teratol 2014;41C: 89–95. Lee BE, Ha EH. Response to commentary “co-exposure and confounders during neurodevelopment: we need them in the bigger picture of secondhand smoke exposure during pregnancy”. Environ Res 2012;112:235. Majewska MD, Dórea JG. Krakow's children and cognitive function: can the study by Jedrychowski et al. show us the bigger picture? Eur J Pediatr 2012;171:405. [author reply 407]. Marques RC, Bernardi JV, Dórea JG, de Fatima R, Moreira M, Malm O. Perinatal multiple exposure to neurotoxic (lead, methylmercury, ethylmercury, and aluminum) substances and neurodevelopment at six and 24 months of age. Environ Pollut 2014; 187C:130–5. Mrozek-Budzyn D, Majewska R, Kieltyka A, Augustyniak M. Neonatal exposure to Thimerosal from vaccines and child development in the first 3 years of life. Neurotoxicol Teratol 2012;34:592–7.
José G. Dórea C.P. 04322, Faculty of Health Sciences, Universidade de Brasilia, 70919-970 Brasilia, DF, Brazil E-mail address: [email protected]. 1 March 2014