The mediating role of maternal inflammation on associations between first-trimester plasticizer exposure and personal-social and language in infants

Abstract

Background: Maternal exposure to bisphenol A (BPA) or phthalates (PAEs) increases inflammation and the risk of neurodevelopmental disorders in offspring. However, limited epidemiological studies have examined the neurodevelopmental effects of co-exposure to them during the first trimester on offspring and their inflammatory mechanism. This study investigates how maternal inflammation mediates the relationship between first-trimester co-exposure to BPA and PAEs and infant neurodevelopment.

Methods: We analyzed 176 mother-child pairs. Maternal exposure to BPA and PAEs (mono-n-butyl phthalate [MBP], monoethyl phthalate [MEP], mono (2-ethylhexyl) phthalate [MEHP]) and 6 types of inflammatory markers were measured in early pregnancy. Infant neurodevelopment was assessed with the Griffiths Development Scales-Chinese. Associations were examined using Spearman correlation, Bayesian kernel machine regression (BKMR), and causal mediation analysis (BKMR-CMA), considering maternal pregestational BMI as a modifier.

Results: During the first trimester, BPA positively correlated with TNF-ɑ and CRP, while MEHP was positively associated with IL-1β. High BPA, MBP, and MEHP levels were negatively linked to infant personal-social development, MEHP was significantly associated with impaired language development. Mediation analysis showed that for personal-social ability, TNF-ɑ (4.80 %) and IL-1β (24.68 %) mediated the effect of mixed exposure at the 75th BMI percentile, while CRP mediated at the 25th (1.35 %) and 75th (11.82 %) percentiles. For language development, at the 25th BMI percentile, TNF-ɑ(28.19 %), IL-1β(50.00 %), and CRP (9.10 %) were significant mediators.

Conclusion: Early pregnancy prenatal BPA and PAE exposure may be associated with delayed personal social and language development, possibly mediated by maternal TNF-ɑ, IL-1β, and CRP, especially in women with inadequate pre-pregnancy BMI.

Keywords: Bayesian kernel regression causal mediation analysis; Bisphenol A; Maternal inflammation; Neurodevelopment; Phthalates; Pre-pregnancy body mass index.