Neonatal urinary phthalate metabolite concentrations predict the development of atopic dermatitis

Background: Maternal phthalate exposure has been linked to the risk of atopic dermatitis (AD) in children. However, maternal urinary measurements may not accurately reflect neonatal exposure. This study investigated whether early neonatal urinary phthalate levels could serve as noninvasive biomarkers for predicting AD and explored potential mechanisms involving immune activation and skin barrier disruption. Methods: Urinary phthalate metabolites were quantified in neonates within 48 hours of birth using liquid chromatography–mass spectrometry. Logistic regression was used to identify phthalate concentrations predictive of subsequent AD development. In vitro, peripheral blood mononuclear cells (PBMCs) and human epidermal keratinocytes (HEKs) were exposed to phthalates to assess cytokine and skin barrier gene expression. Skin barrier function was evaluated by measuring trans-epidermal water loss (TEWL) in organotypic skin models. Results: Neonatal urinary concentrations of di (2-ethylhexyl) phthalate (ΣDEHP) above 12.18 μg/L were strongly associated with later development of AD (adjusted OR, 8.31; 95% CI, 1.74–39.65; p = .008). Exposure to phthalates increased expression of IL-1β, TSLP, TNF-α, and IL-6 in both PBMCs and HEKs ( p < .05), while IL-25 and IL-33 were selectively elevated in HEKs. Phthalates suppressed the expression of filaggrin and loricrin in HEKs and significantly increased TEWL in organotypic skin models ( p < .05), indicating impairment of skin barrier integrity. Conclusion: Elevated neonatal urinary ΣDEHP levels independently predict AD risk. Phthalate-induced inflammation and epidermal barrier dysfunction may contribute to early AD pathogenesis.