Prenatal PFAS exposure and childhood respiratory allergic diseases: Findings from Shanghai Birth cohort Consortium

• A prospective cohort study involving 4,166 mother–child pairs was conducted. • Prenatal exposure to individual and PFAS mixture increased the risk of childhood RAD, particularly allergic rhinitis. • Higher PM 2.5 exposure during pregnancy exacerbated the PFOA-RAD association Per- and polyfluoroalkyl substances (PFAS) pose significant health risks to vulnerable populations such as pregnant women and children. Evidence on prenatal PFAS exposure and childhood respiratory allergic diseases (RAD) is scarce, particularly regarding how this relationship might be modified by prenatal PM 2.5 exposure. To assess the association between prenatal PFAS exposure and the risk of childhood RAD and evaluate whether prenatal PM 2.5 exposure modifies this association. We conducted a population-based prospective cohort study of 4,166 mother–child pairs from the Shanghai Birth Cohort Consortium to investigate this relationship. Data on RAD (including asthma and allergic rhinitis) in children under 8 years of age were collected from medical records or validated questionnaires. Concentrations of seven PFAS were measured in maternal blood collected during early pregnancy using ultra-high performance liquid chromatography/triple quadrupole tandem mass spectrometry. Generalized linear regression models were used to assess the associations between PFAS and childhood RAD after adjusting for potential confounders. Among the participants, 1,003 (23.9%) children were diagnosed with RAD. PFOA exhibited the highest median concentration (11.97 ng/mL), followed by PFOS (9.68 ng/mL). A doubling increment in PFOA was associated with an increased adjusted odds ratio (aOR) for childhood RAD (1.21, 95% CI: 1.03 to 1.41). The molar sum of five carboxylate PFAS (∑PFCAs) were also significantly associated with elevated RAD risk (aOR = 1.21, 95% CI: 1.03 to 1.42). Additionally, we observed that higher prenatal PM 2 . 5 exposure appeared to enhance the adverse effects of PFAS on RAD, with a significant interaction specifically noted for PFOA in relation to allergic rhinitis (aOR = 1.35, 95% CI: 1.07 to 1.72). Prenatal exposure to individual and PFAS mixture was associated with an increased risk of childhood RAD, particularly allergic rhinitis. Children born to mothers with high PM 2 . 5 levels during pregnancy were more susceptible. Reducing prenatal PFAS and PM 2.5 exposure may reduce the public health burden of childhood RAD.