Association of phthalate exposures with urinary free cortisol and 8-hydroxy-2'-deoxyguanosine in early childhood

Several studies suggested potential links of phthalates to stress-related outcomes. However, limited evidence has been available for the relationships between phthalate metabolites and free cortisol and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in perinatal and postnatal environments. Therefore, we evaluated the relationships between phthalate metabolites and free cortisol and 8-OHdG in mother-child pairs. We repeatedly collected urine samples of 287 mother-child pairs from just before delivery to 15 months of age to measure the levels of four phthalate metabolites - mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono-isobutyl phthalate (MiBP), and mono-n-butyl phthalate (MnBP) - and free cortisol and 8-OHdG. We used linear mixed effect models and generalized additive mixed models to estimate the relationship between the phthalate metabolites and free cortisol and 8-OHdG after adjusting for the child's gender, urine collection time, and maternal smoking status. The four phthalate metabolite levels were strongly correlated each other (all, p < .0001), and intra-class correlation for each metabolite in children ranged from 0.18 to 0.96. All four phthalate metabolites were positively associated with both free cortisol (MEHHP, β = 0.18 and p < .0001; MEOHP, β = 0.17 and p < .0001; MiBP, β = 0.13 and p = .0001; MnBP, β = 0.21 and p < .0001; and molar sum of metabolites, β = 0.21 and p < .0001) and 8-OHdG (MEHHP, β = 0.20 and p < .0001; MEOHP, β = 0.18 and p < .0001; MiBP, β = 0.23 and p < .0001; MnBP, β = 0.28 and p < .0001; and molar sum of metabolites, β = 0.29 and p < .0001) in childhood. Our findings suggest that phthalate exposures increase free cortisol and 8-OHdG levels in early childhood.