ReviewTrends in neurodevelopmental disability burden due to early life chemical exposure in the USA from 2001 to 2016: A population-based disease burden and cost analysis
Introduction
Among the detrimental effects of prenatal and early-life chemical exposures are their neurotoxicity. Chemically-induced neurological damage may occur through endocrine and non-endocrine mechanisms (Bennett et al., 2016; Grandjean and Landrigan, 2014). Endocrine disrupting chemicals (EDCs) may exert their effects by altering thyroid receptor or estrogen receptor regulation of neuroendocrine development, or by influencing dopaminergic neuronal development (L. Chen et al., 2017; Ghassabian and Trasande, 2018; Gilbert et al., 2012; Iavicoli et al., 2009; Laessig et al., 1999; Masuo and Ishido, 2011). These chemicals can also affect neurotoxicity through cell damaging mechanisms such as interference with calcium pathways or inducing oxidative stress. This leads to disruption of biologically important processes required for proper neurodevelopment (Bressler and Goldstein, 1991; Ceccatelli et al., 2010; Garza et al., 2006; Naughton and Terry, 2018). Impaired neurodevelopment and resulting neurotoxicity can have a range of consequences, from behavioral problems to learning disabilities to autism spectrum disorder (Gould, 2009).
Research into the adverse health effects of EDCs has contributed to the implementation of more stringent regulatory standards. The best documented example of these changes is the removal of lead from gasoline, paint, and municipal drinking water systems and the subsequent prevention of IQ loss (Bartlett and Trasande, 2014; Grosse et al., 2002). Other regulatory practices have followed, including changes to California's 1975 upholstered furniture flammability standards, for which brominated flame-retardants (BFRs) were primarily used (State of California Department of Consumer Affairs, 1975). In 2013, public concern over the health effects of these chemicals led the state to decrease the amount of time in which furniture must remain smolder resistant, thereby removing the need for additive BFRs. This has influenced furniture and mattress manufacturing standards around the country (State of California Department of Consumer Affairs, 2013). It is a strong hypothesis that decreased EDC exposure may provide benefits for the economy by increasing intellectual capital and economic productivity, and for society through the reduction of crime and other negative behaviors (Grosse et al., 2002).
Despite these improvements, no study has documented how EDC regulations in the United States have affected health and associated economic costs. The National Health and Nutrition Examination Surveys (NHANES) provide a wealth of human biomonitoring data beginning in 1999 in which chemical levels are examined in a representative sample of the population. We examined trends in intellectual disability burden, IQ loss, and associated potential costs from 2001 to 2016 as a result of in utero and early life exposure to endocrine disrupting chemicals in the United States from 1999 to 2014.
We chose to focus this study on four major EDCs—polybrominated diphenyl ethers (PBDEs), organophosphates (OPs), methylmercury, and lead—given the extensive research on their ability to cause neurodevelopmental damage and cross the placental barrier (Bressler and Goldstein, 1991; Ceccatelli et al., 2010; L. Chen et al., 2017; Garza et al., 2006; Ghassabian and Trasande, 2018; Gilbert et al., 2012; Iavicoli et al., 2009; Laessig et al., 1999; Masuo and Ishido, 2011; Naughton and Terry, 2018; Yang et al., 2019). We restricted our analysis to the prenatal period for PBDE, organophosphate, and methylmercury exposure, as the developing fetus is at greatest risk for neurodevelopmental toxicity. For lead, we examined early life exposure (children from birth up to the age of five).
Section snippets
Population data and chemical exposures
We obtained nationally representative human biomonitoring data including chemicals from the National Health and Nutrition Examination Survey (NHANES). Sponsored by the National Centers for Health Statistics of the Centers for Disease Control and Prevention, NHANES is a nationwide probability sample of the US civilian noninstitutionalized population aged one to 74 years. The goal of the surveys has been to assess the health and nutritional status of adults and children in the United States
Results
Trends of lead, methylmercury, PBDE, and organophosphate-attributable IQ point loss over time are shown in Fig. 1. In utero exposure to PBDE represented the highest burden in neurodevelopmental impairment but showed an overall declining effect from 2008 to 2016. Lead-attributable IQ point loss in children under the age of five also showed an overall decrease, especially from 2004 to 2014. In utero methylmercury exposure had the smallest effect on IQ and experienced only a slight decrease
Discussion
This analysis of NHANES chemical biomarker data shows how chemical exposure regulation can affect the health of children and neonates. From 2001 to 2016, exposure to these chemicals cost over $6 trillion due to loss of IQ points alone. However, these results show that better regulatory efforts may have decreased exposure to PBDEs, lead, and methylmercury, thereby preventing neurodevelopmental disability. This study adds to previously published papers that demonstrate the contribution of
Conclusions
Although costs of regulation are frequently used to support the free use of chemicals in industry, our findings show that the reduction of chemical exposures in early life has already resulted in economic savings on the order of billions of dollars. Though further research is needed, these findings indicate that large societal benefits can result from reducing children's exposure to toxic chemicals. However, increased regulation forces the use of alternative, and possibly untested, chemicals.
Funding
This work was supported by the National Institutes of Health [grant numbers ES022972 and ES029779].
Declaration of competing interest
None.
Acknowledgements
We would like to thank Dr. Bruce P. Lanphear for his work modeling the exposure-response relationships with the chemicals reported in this study, which served as the basis for our analysis.
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