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Background: The structural similarity between sex hormones and exogenous phthalates (PAEs) enabled them as disrupters in regulating childhood blood pressure (BP). We aim to explore the association of sex hormones homeostasis and PAEs metabolites with childhood high BP (HBP). Methods: A cohort study was conducted with 1416 children aged 7–13 years at baseline and with 824, 819, and 801 children completing three waves' follow up. Serum testosterone (TT) and estradiol (E2) in children during three consecutive waves of surveys were measured by radioimmunoassay, and then TT/E2 ratio calculated as TT divided by E2 were used to represent sex hormones homeostasis. Seven urinary PAEs metabolites were measured in children of first wave. The BP Z-Scores and HBP across waves were obtained by sex, age, and height specific percentiles. Log-binomial regression models with adjusted risk ratios (aRR) after adjusting for confounders were utilized. Results: The prevalence of HBP at the baseline survey was 25.5%, and increased from 26.3% in the first wave of survey to 35.0% in the third wave of survey. PAEs were negatively correlated with E2, while positively correlated with TT and TT/E2 ratio. A positive association of the serum TT levels, TT/E2 ratio, and total PAEs was found with HBP prevalence (in wave 1, 2 and 3 with TT (aRR): 1.63, 1.37 and 1.45; with TT/E2: 1.63, 1.42 and 1.20; with PAEs: 1.40, 1.32 and 1.32), persistent HBP (with TT (aRR): 2.19; TT/E2: 2.16; PAEs: 2.57), occasional HBP (with TT (aRR): 1.94; TT/E2: 1.72; PAEs: 1.38), and new HBP incidence (with TT (aRR): 1.44; TT/E2: 1.57; PAEs: 1.67), but E2 had a negative association with HBP phenotypes (HBP prevalence in wave 1, 2 and 3 (aRR): 0.77, 0.93, and 1.10; persistent HBP: 0.47; occasional HBP: 0.96; new HBP incidence: 0.81). The E2 and PAEs had antagonistic effects on HBP risks in children, particularly in girls and those with high BMI group, but the TT levels, TT/E2 ratio and PAEs had synergistic effects on HBP risks in children, particularly in boys and those with high BMI group. Conclusion: Exogenous PAEs exposure and endogenous sex hormones homeostasis disruption independently increase the risks of HBP. Moreover, the exogenous PAEs exposure could disrupt the endogenous sex hormones homeostasis in children, thereby combinedly increased risks of childhood HBP.

Background: There was growing interest in endocrine disrupting chemicals that might have effect on the obesity epidemic, but few studies on the association of phthalates (PAEs) with childhood overweight and obesity in China based on longitudinal cohort study were available, which was the purpose of the present study. Methods: A nested case-control study was conducted in a prospective cohort of 2298 children aged 7–13 years from October 2017 to October 2020 with five waves visits in Xiamen city, China. A total of 829 children remained in the first wave of follow up with collection of urine for measuring seven PAEs metabolites, including mono-methyl phthalate (MMP), mono-ethyl phthalate (MEP), mono-n-butyl phthalate (MBP), mono-iso-butyl phthalate (MiBP), mono-2-ethylhexyl phthalate (MEHP), mono-2-ethyl-5-oxohexyl phthalate (MEOHP) and mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP), utilizing ultra high performance liquid chromatography-triple quadrupole mass spectrometry. Overweight and obesity, defined by WHO classifications, were allocated to the cases group, and those of all normal weight and matched cases with normal weight in each wave of follow-up as two control groups. Logistic regression models after adjusting for confounders were utilized to analyze the effect of PAEs on overweight and obesity in children with divided four groups based on the quartile distribution of each and total PAEs concentration. Results: The detection rates of children for each PAEs metabolite were 99.4% for MMP, 99.4% for MEP, 99.8% for MBP, 54.5% for MEHP, 84.4% for MEOHP, 99.9% for MEHHP, and 97.2% for MiBP. The geometric mean of concentrations of PAEs, MMP, MEP, MBP, MEHP, MEHHP, and MiBP were 310.085, 34.658, 9.127, 166.347, 7.043, 3.400, 18.571, and 24.093 (ng/ml), respectively. The total PAEs and seven metabolites concentrations were positively associated with childhood BMI Z-Scores with statistically significant slope rates and correlation coefficients, and were higher in the cases group than those in two controls groups in each wave of follow-up. The PAEs concentrations in the cases group was 5.90 (95 %CI: 5.79, 6.01) ng/ml in the first wave of survey, which was higher than those normal controls group (5.68 (95 %CI: 5.61, 5.75) ng/ml, P