Neonatal urinary phthalate metabolite concentrations are associated with the development of atopic dermatitis

Perinatal phthalate exposure has been suggested as a potential cause of atopic dermatitis (AD).

To investigate whether neonatal urinary phthalate levels may serve as predictors of AD development and to explore mechanisms involving immune activation and skin barrier impairment.

Urinary phthalate metabolites collected within 48 hours of birth were analyzed by liquid chromatography-tandem mass spectrometry. AD at 12 months was identified through physician diagnosis and treatment history. Logistic regression was used to evaluate the association between phthalate levels and AD. Peripheral blood mononuclear cells (PBMCs) and human neonatal epidermal keratinocytes (HEKs) were exposed to phthalates to assess cytokine and skin barrier protein expression, and trans-epidermal water loss (TEWL) was measured in organotypic skin models.

Among 61 neonates, 11 (18.0%) developed AD by 12 months of age. Neonatal urinary concentrations of di(2-ethylhexyl) phthalate were associated with the development of AD (adjusted OR, 2.03; 95% CI, 1.12-3.68; p = 0.020). Phthalates increased expression of IL-1β in PBMCs (1.54-fold, 95% CI 1.27-1.81) and HEKs (1.23-fold, 95% CI 1.11-1.36), and similarly elevated TNF-α (1.29-fold, 95% CI 1.16-1.42; 1.80-fold, 95% CI 1.22-2.39), and IL-6 (1.55-fold,95% CI 1.36-1.74; 1.96-fold, 95% CI 1.31-2.62). Phthalates suppressed protein expression of filaggrin (0.67-fold, 95% CI 0.34-1.00) and loricrin (0.66-fold, 95% CI 0.35-0.97) in HEKs and increased TEWL in organotypic skin models (1.43-fold, 95% CI 5.21-19.61).

Elevated neonatal urinary phthalate metabolites are associated with an increased risk of AD development. Phthalate-induced skin barrier dysfunction may contribute to early onset of AD.

The study was registered in the Clinical Research Information Service (CRiS), Republic of Korea, which is part of the WHO International Clinical Trials Registry Platform (registration number: KCT0007286).