Racial and ethnic differences in the association between pediatric phthalate exposures and antibody response to vaccination from NHANES 2015-2016

Background: Phthalates are endocrine-disrupting chemicals widely present in consumer products. Increasing evidence suggests phthalates may impair immune responses, including antibody production following vaccination. Racial and ethnic disparities in phthalate exposure have been documented in the United States, yet little is known about whether associations with vaccine-induced immunity differ across sexes and racial/ethnic groups. Methods: Data from the 2015-2016 National Health and Nutrition Examination Survey (NHANES) were analyzed for 387 children aged 6-17 years with complete data on urinary phthalate metabolites, serum antibody concentrations against tetanus and pertussis, and relevant covariates. Linear regression, Quantile G-computation, and Bayesian Kernel Machine Regression (BKMR) were used to evaluate associations between phthalates and antibody levels, with models adjusted for age, sex, BMI, family income-to-poverty ratio, and creatinine. Sex and racial/ethnic differences were evaluated in stratified analyses. Results: Two phthalate metabolites, mono-(2-ethylhexyl) phthalate (MEHP) and mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), were negatively associated with tetanus and pertussis antibody concentrations in individual chemical analysis, with antibody levels approximately 10-12% lower for each doubling of exposure, several associations remained after correction for multiple testing comparisons. In stratified analyses, associations were more pronounced among females and White children. Using quantile g-computation, the phthalate mixture was associated with lower pertussis antibody levels in females (ψ = −0.26; 95% CI: −0.51, −0.01), but not in males or in the overall population. Grouped analyses of correlated metabolites (e.g., ∑ DEHP) revealed inverse associations with antibody levels, particularly in females. Bayesian Kernel Machine Regression did not identify statistically significant overall mixture effects, but suggested heterogeneity driven by specific metabolites. Conclusions: Higher phthalate exposures were associated with lower vaccine-induced antibody concentrations in U.S. children, with potential sex and racial/ethnic differences. These findings underscore the importance of addressing environmental exposures as contributors to health disparities in the US.