Phthalate Mixture Exposure is Associated with Elevated Blood Pressure in Chinese Children: A Panel Study

There is unclearly epidemiological evidence regarding relations of phthalates (PAEs) with children’s blood pressure (BP) and its potential mechanism. We designed a panel study with up to 3 repeated visits over 3 seasons. Total of 103 children aged 4–13 years were available with 287 measurements of urinary PAEs metabolites (mPAEs), BP and serum cytokines. We evaluated associations of mPAEs, either as individual or as mixture, with systolic/diastolic BP (SBP/DBP), mean arterial pressure (MAP) and hypertension, and in which the role of serum cytokines played. After multiple comparisons, positive associations of mono-iso-butyl phthalate with SBP, mono-ethyl phthalate (MEP), mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP) with DBP, MEP with MAP were the most robust ( P - FDR < 0.05), while a marginal relation of MECPP and hypertension was also observed ( P - FDR = 0.07). Such relationships showed in a dose–response manner and were stronger in children with dyslipidemia. Meanwhile, weighted quantile sum regression analyses indicated the associations of mPAEs mixture with DBP and MAP elevation, which were dominated by MEP, MECPP and mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP). Furthermore, BP-related mPAEs were positively linked with multiple cytokines, however, only PDGF, IL-16 respectively mediated 7.76% and 12.23% in MEP-related MAP elevation. Accordingly, urinary PAEs were dose-responsive related to elevated BP and risk of hypertension with the highest weight in MEP, MECPP and MEHHP, in which PDGF, IL-16 might be partly involved among children.