Furong Wang, Yutao Li, Jing Li, Xi Ling, Huan Yang, Yangyang Pi, Xue Li, Liwen Zhang, Da Chen, Gongli Chen, Jia Cao, Qing Chen, Shengzhi Sun, Niya Zhou
These findings characterize the maternal-fetal distribution of BHT and its TPs among pregnant women in Southwest China and identify associations of maternal BHT-derived TPs with GDM and related metabolic alterations.
Synthetic phenolic antioxidants (SPAs) and their transformation products (TPs) are widespread environmental contaminants with endocrine-disrupting potential, yet their distribution across the maternal-fetal interface and relevance to maternal metabolic health remain unclear. Leveraging 222 paired maternal and umbilical cord plasma samples (51 cases of gestational diabetes mellitus [GDM] and 171 normoglycemic controls) from the Chongqing Preconception Reproductive Health and Birth Outcome Cohort (PREBIC), we quantified eight SPAs (AO246, DTBSBP, DtAP, AO2246, 4-tOP, BHA, 2,4-DtBP, and BHT) and five BHT-derived TPs (BHT-OH, BHT-CHO, BHT-COOH, BHT-quinol, and BHT-Q) using UPLC-MS/MS and performed targeted metabolomic profiling of 446 maternal plasma metabolites. In maternal plasma, 2,4-DtBP and BHT were the predominant compounds, whereas BHT-derived TPs, particularly BHT-Q and BHT-quinol, predominated in umbilical cord plasma. The transplacental transfer efficiency of BHT-quinol was significantly lower in GDM pregnancies. Maternal plasma concentrations of BHT-quinol and total TPs were higher in women with GDM. Each one-unit increase in ln-transformed BHT-quinol and total TP concentrations was associated with higher odds of GDM (adjusted odds ratio [OR], 1.83; 95% CI: 1.34-2.59; adjusted OR, 1.49; 95% CI: 1.08-2.11, respectively). Bayesian kernel machine regression identified BHT-quinol as the dominant contributor to the observed positive mixture-GDM association. Integrative metabolomic analyses identified 88 overlapping lipid metabolites showing consistent inverse associations with both maternal BHT-quinol concentrations and GDM status, with enrichment in pathways related to AGE-RAGE signaling in diabetic complications, sphingolipid signaling, and insulin resistance. These findings characterize the maternal-fetal distribution of BHT and its TPs among pregnant women in Southwest China and identify associations of maternal BHT-derived TPs with GDM and related metabolic alterations. Prospective studies are warranted to clarify the potential causal relationships between SPA exposure and maternal metabolic health.