Prenatal phthalate exposures and childhood allergies: Combined linear/nonlinear modeling reveals critical windows and sex differences

Prenatal phthalate exposure and childhood allergies remain understudied. This study analyzed 3240 singleton mother-infant pairs from the Ma'anshan Birth Cohort. Urine samples were collected during all three trimesters to detect phthalate metabolites. Childhood allergic diseases, which included recurrent wheezing (RW), atopic dermatitis (AD), and allergic rhinitis (AR), were longitudinally assessed using a self-designed questionnaire incorporated items adapted from ISAAC. A nonlinear association existed between first-trimester exposure to low-molecular-weight phthalates (MMP, MEP, MBP) and childhood RW risk, with cumulative exposure amplifying this risk. Individual metabolites (MMP, MBP, and MEOHP) exhibited linear/nonlinear associations with AD, cumulative exposure was nonsignificant. Early rhinitis risk in girls demonstrated an inverse U-shaped relationship with prenatal exposure to a specific DEHP metabolite, with third-trimester exposure reducing risk. Notably, cumulative exposure to phthalates during the third-trimester reduced the risk of rhinitis in children. However, cumulative phthalate exposure during first-trimester increased the risk of developing rhinitis in children, which was driven primarily by nonlinear associations of DEHP metabolites in early pregnancy with rhinitis risk. Second-trimester cumulative exposure also increased the risk of rhinitis in children, primarily due to MBP-associated early rhinitis susceptibility. Importantly, all associations were sex-specific. This study highlights trimester- and sex-dependent effects of prenatal phthalate exposure on childhood allergies, emphasizing nonlinear dose-response relationships. Future studies are needed to confirm these findings.