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Environmental toxicology and pharmacology · 2025

Maternal immune-inflammatory markers mediate the association between urinary phthalate metabolites and preeclampsia.

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Tao Lin, Dai Lulu, Xiong Shimin, Liao Dengqing, Zhou Yuan-Zhong, Shen Xubo

Аннотация

BACKGROUND: This study aimed to comprehensively investigate the associations among maternal immune-inflammatory markers and urinary phthalate (PAE) metabolites during pregnancy, focusing on their potential links with preeclampsia and related reproductive outcomes.

METHOD: A propensity score-matched case-control design was adopted, enrolling 61 cases and 118 controls matched based on propensity scores. To assess associations, dose-response relationships, and mediating effects, multiple statistical methods were employed, including logistic regression, restricted cubic splines (RCS), Bayesian kernel machine regression (BKMR), and structural equation modeling (SEM).

RESULTS: Maternal urinary metabolites of PAEs (MEHP, MEHHP) and the systemic immune-inflammation index (SII) were significantly higher in the case group than in the control group. Logistic regression analysis revealed positive associations between MEHP, MOP, MEHHP, SII, and preeclampsia (all odds ratios [OR] > 1, P < 0.05). RCS analysis revealed nonlinear dose-response relationships for MOP and SII, with threshold concentrations of 2.57 μg/L creatinine (MOP) and 977.24 μg/L (SII). BKMR results indicated a nonlinear positive correlation between PAE metabolites, immune-inflammatory markers, and spontaneous abortion. SEM models confirmed mediating effects of immune-inflammatory markers: SII mediated the associations between MEHP, MOP, MEHHP and preeclampsia with mediation rates (95 %CI) of 8.73 % [1.33 %-22.34 %], 25.31 % [11.72 %-36.00 %], and 6.50 % [0.36 %-21.39 %], respectively; AISI mediated the MEHP-preeclampsia association (0.27 % [0.20 %-1.19 %]); and MLR and PLR mediated the MEHHP-preeclampsia association (2.54 % [1.53 %-8.80 %] and 7.59 % [1.20 %-12.52 %], respectively).

CONCLUSION: Maternal urinary PAE metabolites during pregnancy are associated with an increased risk of preeclampsia, and maternal immune-inflammatory markers partially mediate this relationship. These findings provide insights into the potential mechanisms linking prenatal PAE exposure to adverse pregnancy outcomes.

Предметные рубрики MeSH

ИП Урсолов Владлен Сергеевич

ИНН 500118482352 · ОГРНИП 314500117700049

Реквизиты и контакты