Association of maternal bisphenol exposure during pregnancy with spontaneous preterm birth and preliminary mechanistic exploration in a prospective cohort

Objective: This study aimed to examine the associations between trimester-specific bisphenol exposure and preterm birth (PTB) and explore potential underlying mechanisms.

Methods: Within the Tongji Precision Birth Cohort (TPBC), concentrations of ten bisphenols were quantified using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Multivariable logistic regression models were employed to examine associations between trimester-specific urinary bisphenol exposure and spontaneous PTB (sPTB). Placental expressions of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were evaluated by immunohistochemistry. Median urinary concentrations of Bisphenol A (BPA) and BPF were used to guide in vitro assays. HTR8 and BeWo trophoblast cell lines were exposed to gradient BPA and BPF. RT-qPCR was used to measure mRNA levels of NF-κB pathway-related genes.

Results: Among the bisphenols analyzed, BPF emerged as the most common alternative to BPA. Placental BPA and urinary BPF showed associations with sPTB risk. Each standard deviation increase in placental BPA concentration was associated with a 38.1% increased risk of spontaneous preterm birth (95% CI: 1.023-1.866, p = 0.035). Placental expression of IL-6 and TNF-α was increased in sPTB. In trophoblast cells, low to middle concentrations of BPA and BPF might upregulate NF-κB pathway-related genes and selected inflammatory markers.

Conclusions: Bisphenol exposure during pregnancy, particular BPA and BPF, may be associated with increased risk of sPTB. The findings further suggest the involvement of NF-κB pathway-related placental inflammatory signaling.