Prenatal Parabens Exposure and Infantile Eczema: Mediation by IL-17A, Effect Modification by Breastfeeding, and Evidence from Network Toxicology.

Background

Prenatal exposure to parabens (PBs) has been associated with infantile eczema; however, the mediating role of inflammatory cytokines and the potential modifying effect of breastfeeding remain unclear.

Methods

This prospective study included 336 mother-infant dyads. Maternal serum concentrations of five parabens, namely methylparaben (MeP), ethylparaben (EtP), propylparaben (PrP), butylparaben (BuP), and hexylparaben (HeP), and eight inflammatory cytokines were measured during pregnancy. Infantile eczema and feeding patterns during the first six months were recorded. Weighted quantile sum (WQS) regression assessed mixture effects; single-chemical associations were examined using covariate-adjusted logistic and linear regression. Mediation and moderated mediation analyses were performed to evaluate the role of interleukin-17A (IL-17A) and the modifying effect of breastfeeding. Network toxicology was employed to identify shared molecular targets and pathways.

Results

The PBs mixture was significantly associated with increased eczema risk (WQS OR = 1.97, 95% CI: 1.24-3.12). In single-chemical models, PrP (OR = 1.08, 95% CI: 1.02-1.15) and HeP (OR = 1.38, 95% CI: 1.02-1.87) were positively associated with eczema. Maternal PrP was positively associated with serum IL-17A (β = 0.034, 95% CI: 0.006-0.063). Elevated IL-17A was strongly associated with eczema (OR = 3.46, 95% CI: 1.45-8.26). IL-17A accounted for approximately 14.9% of the association between PrP and eczema (indirect effect β = 0.003, 95% CI: 0.001-0.010). Moderated mediation revealed that breastfeeding significantly modified the pathway from IL-17A to eczema (interaction P = 0.018). The indirect effect was significant only in formula-fed infants (β = 0.069, P = 0.040) and absent in breastfed infants (P = 0.680). Network toxicology identified 11 common targets of PrP and eczema enriched in IL-17, Toll-like receptor, and NF-κB signaling pathways.

Conclusions

Maternal IL-17A may partially mediate the association between prenatal PrP exposure and infantile eczema, and breastfeeding may modify the association between IL-17A and eczema. These findings support the importance of further evaluating prenatal paraben exposure during pregnancy and promoting breastfeeding to mitigate early-life allergic disease risk.