Effect modification of maternal concentrations of per- and polyfluoroalkyl substances on vaccine effectiveness in children up to 6 years of age: The Japan Environment and Children's Study.

Epidemiological evidence suggests that per- and polyfluoroalkyl substances (PFAS) exposure may attenuate antibody responses to vaccination. However, vaccine effectiveness as an outcome has not been investigated. This study assessed whether maternal PFAS concentrations during pregnancy modified childhood vaccine effectiveness. We analyzed mother-child pairs from the Japan Environment and Children's Study. Children's vaccination status for varicella, mumps, and influenza was collected via self-reported questionnaires at 2 years of age. Subsequent infection incidence was similarly assessed until 6 years for varicella and mumps, and 3 years for influenza. Maternal plasma samples collected during pregnancy provided PFAS measurements. Logistic regression models, incorporating interaction terms between vaccination status and PFAS concentrations, examined effect modification on both additive (relative excess odds due to interaction) and multiplicative (ratio of odds ratios) scales. Vaccinations were associated with reduced infection risk across PFAS exposure levels for all three diseases. Effect modification assessments revealed that perfluorononanoic acid (PFNA) significantly reduced varicella and mumps vaccine effectiveness on the additive scale. For mumps, the odds ratio for infection among unvaccinated versus vaccinated children (higher values indicate greater vaccine effectiveness) was higher in the lowest PFNA tertile than in the highest, with a relative excess odds due to interaction of 0.94 (95% confidence interval: 0.33-1.54, P = 0.0025). Multiplicative scale effect modifications were not statistically significant. Vaccinations reduced infections in children across all maternal PFAS exposure levels. Evidence of effect modification was limited, isolated, and inconsistent. These analyses are exploratory, and confirmation is warranted.