Prenatal polycyclic aromatic hydrocarbon (PAH) exposure, antioxidant levels and behavioral development of children ages 6–9

Highlights

• Lower antioxidants levels may harm neurodevelopment after adjusting for PAH levels.

• No interaction was present between antioxidants and PAH on CBCL symptoms.

• Future research is needed to confirm these findings.

Abstract

Purpose

Prenatal polycyclic aromatic hydrocarbon (PAH) exposure has been shown to increase DNA adduct levels and to affect neurodevelopment. Micronutrients may modify the adverse effect of PAH on neurodevelopment. Thus, we examined if micronutrient concentrations modified the association between PAH exposure and neurodevelopmental outcomes.

Methods

151 children from a birth cohort who had micronutrient concentrations measured in cord blood and completed the Child Behavioral Checklist (CBCL), between the ages of 6 and 9 years, were evaluated. Prenatal airborne PAH exposure was measured by personal air monitoring. The betas and 95% CI for the associations of antioxidant concentrations and PAH exposure with each of the outcomes of CBCL raw score and dichotomized standardized T-score (based on clinical cutpoints) were estimated, respectively, by multivariable poisson and logistic models.

Results

Children below the median for alpha-tocopherol and gamma-tocopherol concentrations, compared to those above, were more likely to have thought problems, aggressive behavior and externalizing problems (p<0.05). Lower carotenoid concentration was associated with more thought problems (MVβ=0.60, p<0.001) and externalizing problems (MVβ=0.13, p<0.05) for the same contrast. No statistically significant associations were observed between retinol concentrations and neurodevelopmental symptoms. Overall, no consistent patterns were observed when we examined the interaction between antioxidants (e.g., alpha-tocopherol) and PAH in relation to CBCL symptoms (e.g., internalizing and externalizing problems, p<0.05).

Conclusions

Lower alpha-tocopherol, gamma-tocopherol and carotenoid levels may adversely affect healthy neurodevelopment, even after accounting for PAH exposure. Future research to confirm these findings are warranted given the importance of identifying modifiable factors for reducing harmful PAH effects.

Introduction

Polycyclic aromatic hydrocarbons (PAH) are a group of pollutants due to incomplete combustion of carbon sources stemming from industrial activities, coal heating, vehicle exhaust, as well as tobacco smoke, and grilled foods (Guo et al., 2011). Exposure to PAHs can result in genotoxic effects, DNA damage through DNA adduct formation, and dysregulation of the epigenome (Farmer et al., 2003, Jedrychowski et al., 2013, Perera and Herbstman, 2011, Perera et al., 2005). Most prior research has been conducted in adults; however, evidence over the last decade has emerged showing that prenatal and early life exposure to PAH has effects on fetuses and infants, and may result in long term detrimental effects (Perera et al., 1999). For example, higher prenatal PAH exposure was inversely associated with measures of fetal growth, such as birth weight and head circumference, and neurodevelopment outcomes in children (Jedrychowski et al., 2003). Within two birth cohorts in the United States and Poland, prenatal PAH exposure was associated with poor cognitive development and intelligence, as well as behavioral problems, in children measured at three to seven years of age (Edwards et al., 2010, Perera et al., 2009, Perera et al., 2006, Perera et al., 2012, Perera et al., 2013). Given the potential long term consequences of prenatal and early life exposure to PAH, reduction of exposure to PAH and identification of modifiable risk factors that modulate downstream effects of PAH exposure are crucial.

Micronutrients, particularly antioxidants, found in fruits and vegetables, oils and nuts and supplemental forms, may modulate PAH exposure by quenching free radicals, reducing DNA adduct formation (Kelvin et al., 2009), and ultimately preventing harmful downstream effects, such as poor health (Masters et al., 2007, Pedersen et al., 2013) and neurodevelopmental outcomes. In particular, alpha-tocopherol (Vitamin E) has been shown to be critical for fetal growth, normal neurological function and development of the nervous system (Kiely et al., 1999a, Kiely et al., 1999b, Masters et al., 2007). Similarly, retinol (Vitamin A) is essential for postnatal brain development activities such as learning and spatial memory (Haga et al., 1982). In addition, carotenoids seem to exhibit protective effect against Benzo(a)Pyrene (B(a)P)-induced oxidative stress and DNA damage (Azqueta and Collins, 2012), possibly by combating oxidative stress via free radical scavenging activity (Baydas et al., 2002a, Baydas et al., 2002b). However, to date, no study has analyzed the modulating effect of micronutrient levels on the association between prenatal and early life exposure to PAH and the behavioral development of children. Thus, within a well characterized birth cohort based in Krakow, Poland, we examined the interaction effects of antioxidant micronutrient concentrations and prenatal PAH exposure, measured by air concentrations of eight PAH carcinogens, on neurodevelopment of children.