Association between Biomarkers of Phthalate Exposure and Serum Folate Concentrations in Children: A Population-Based Cross-Sectional Study of the NHANES from 2011 to 2016

Background: Although adverse health effects of phthalates have been reported, very few studies have assessed the associations between biomarkers of phthalate exposure and serum folate concentrations in children. Objectives: We aimed to examine the association between urinary phthalate metabolites, as biomarkers of exposure to phthalates, and total serum folate concentrations in children using national data from the United States. Methods: We conducted cross-sectional analyses of 2100 individuals aged 6 - 18 y enrolled in the National Health and Nutrition Examination Survey, 2011 - 2016. Multivariable linear regression was applied to examine the relationship between natural logarithm (ln)-transformed urinary phthalate metabolites and serum folate concentrations. The quantile-based g-computation was used to assess the association of urinary phthalate metabolite mixture with serum folate levels. Subgroup analyses were conducted by sex, age, and race/ethnicity, and the interactions were assessed by adding interaction terms of these stratifying variables and phthalates and modeling through the Wald test. Results: In multiple linear regression models, for participants in the highest tertile of MEHHP, MEOHP, DEHP, MCPP, and MCOP, total serum folate concentrations were 1.566 [ beta : - 1.566; 95% con fi dence interval: - 2.935, - 0.196], 1.423 ( - 1.423; - 2.689, - 0.157), 1.309 ( - 1.309; - 2.573, - 0.044), 1.530 ( - 1.530; - 2.918, - 0.142), and 1.381 ( - 1.381; - 2.641, - 0.122) ng/mL lower than those in the lowest tertile. The inverse associations were consistent in different subgroups by sex, age, and race/ethnicity ( P for interaction >= 0.083 for all). In addition, the phthalate mixture showed a strong inverse correlation with serum folate; a quartile increase in the phthalate mixture on the ln scale was associated with 0.888 ( - 0.888; - 1.677, - 0.099) ng/mL decrease in the serum folate. Conclusions: Higher concentrations of urinary phthalate metabolites were associated with lower serum folate concentrations in children. Although our fi ndings should be validated through additional population and mechanistic studies, they support a potential adverse effect of phthalate exposure on folate metabolism in children.