Prenatal per- and polyfluoroalkyl substance levels and childhood rubella incidence up to age 6 years: the Japan Environment and Children’s Study

Per- and polyfluoroalkyl substances (PFAS) have raised concerns about their potential immunosuppressive effects. However, the association between prenatal PFAS exposure and childhood rubella remains unclear. This study examined whether prenatal PFAS exposure is associated with childhood rubella incidence. We analyzed data from the Japan Environment and Children's Study, including children whose mothers had plasma PFAS concentrations measured during pregnancy. The primary outcome was caregiver-reported physician-diagnosed rubella up to 6 years of age. Seven PFAS with detection frequencies >60% were analyzed. Logistic regression analyses were performed to evaluate associations between PFAS concentrations and rubella incidence. Age-stratified analyses were performed, mixture effects were evaluated using quantile g-computation, and a nested case-control sensitivity analysis using conditional logistic regression was conducted. Of 25,253 eligible children, 15,694 were included after excluding non-first-born children from multiple births and participants with missing data; 43 had caregiver-reported physician-diagnosed rubella. No significant associations were observed between maternal PFAS concentrations and childhood rubella incidence in either the regression or age-stratified analyses. Mixture exposure analyses also showed no significant association, and the nested case-control sensitivity analysis yielded similar findings. In conclusion, we did not find a statistically significant association between maternal PFAS exposure during pregnancy and childhood rubella incidence up to 6 years of age. However, the limited number of rubella cases reduced statistical power to detect modest associations, and larger studies are warranted.