Prenatal exposure to organophosphate ester flame retardants and plasticizers and maternal immune responses in three ECHO cohorts.
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Organophosphate ester (OPE) flame retardants and plasticizers may alter maternal immune responses; yet epidemiologic evidence in pregnant populations remains limited. We pooled data from 410 pregnant participants across three Environmental influences on Child Health Outcomes (ECHO) Cohort sites. During mid-to late-pregnancy, spot urine was collected for OPE metabolite quantification, followed by plasma/serum collection for immune markers on the same day or thereafter. Twelve immune markers available in at least two sites were included. We estimated associations between log2-transformed OPE metabolite concentrations and log2-transformed, site-specific z-scored immune marker levels using linear mixed-effects regression with site as a random effect for pooled analyses, and linear regression for site-specific analyses. We conducted exploratory analyses to evaluate effect modification by race/ethnicity, pre-pregnancy obesity, and fetal sex. We observed associations between bis(1,3-dichloro-2-propyl) phosphate and elevated interleukin (IL)-8 levels in the pooled sample (β per doubling = 0.06, 95% confidence interval [CI]: 0.02-0.11) and in both contributing sites. Associations between other OPE metabolites and immune markers were not consistently observed across study sites. Participants with a race/ethnicity other than non-Hispanic White showed stronger associations of diphenyl phosphate (β = 0.16, 95% CI: 0.04-0.28) and bis(2-chloroethyl) phosphate (β = 0.04, 95% CI: -0.01-0.09) with higher tumor necrosis factor-α. Sex-dimorphic associations for IL-6 were observed, with directions varying by OPE metabolite. This U.S. multi-site study suggests certain OPE exposure may be positively associated with maternal IL-8 levels. Such immune responses could alter the intrauterine environment, warranting further investigation into the downstream effects on child health, given the limited current evidence.