Urinary phthalate metabolites and metabolic syndrome in U.S. adolescents: Cross-sectional results from the National Health and Nutrition Examination Survey (2003-2014) data.

OBJECTIVE: There is limited research on the association between phthalates and metabolic syndrome (MetS). Among adolescents, phthalate exposure, which can occur from multiple sources, has been linked to several risk factors for MetS. The objective was to investigate the association between urinary phthalate metabolite concentrations (i.e., mono-ethyl phthalate (MEP), mono-n-butyl phthalate (MnBP), mono-isobutyl phthalate (MiBP), mono-benzyl phthalate (MBzP), mono-(3-carboxylpropyl) phthalate (MCPP), and di(2-ethylhexyl phthalate (DEHP)) and MetS in adolescents aged 12-19 years using the National Health and Nutrition Examination Survey (NHANES) data (2003-2014). A secondary aim was to assess if observed associations varied by a measure of socioeconomic status, economic adversity, which was defined using parental income and educational attainment as well as household food security.

METHODS: We used NHANES data which included physical examination, laboratory urinalysis and fasting blood profiles, and self-reported health characteristics and demographics. Physical examination and laboratory data were used to obtain values of MetS components and urinary phthalate metabolites. We created age-, sex-, and survey year-specific tertiles of creatinine-corrected urinary phthalate metabolites. Analysis was performed using appropriate weighting procedures that accounted for NHANES' complex sampling design. After univariate and bivariate analyses, we performed adjusted logistic regressions to test for associations between individual phthalate metabolites and MetS as well as MetS components and number of MetS components, separately, using the lowest tertile as the reference category. A cross-product term (phthalate metabolite*economic adversity) was subsequently added to adjusted models.

RESULTS: Among 918 participants (mean age 16 years, 45% female, 18% with economic adversity), the prevalence of MetS was 5.3%. Prior to adjustment, adolescents with MetS had marginally higher concentrations of phthalate metabolites than adolescents without MetS. There was a suggestive positive association between intermediate concentrations of MnBP and odds of MetS after adjustment (T2: Odds Ratio (OR) = 2.66 (95% confidence interval: 0.98-7.24); T3: OR = 2.11 (0.71-6.27)). Males with higher MnBP concentrations had higher odds of dyslipidemia; however, associations were mostly non-significant for females. Relationships between MiBP concentrations and odds of MetS varied by sex. Males with higher concentrations of MnBP and MiBP had greater odds of having a higher number of MetS components. Relationships between phthalate metabolites and MetS did not vary by economic adversity.

CONCLUSION: There was a suggestive positive association between MnBP and MetS among adolescents. Associations between phthalate metabolites and MetS as well as MetS components may vary by sex, but may not vary by economic adversity. Further research of the relationships between phthalate exposures, MetS, and potential interactions with socioeconomic factors is warranted.