Prenatal exposure to organophosphate ester flame retardants and child cognition: Findings from the environmental influences on child Health Outcomes cohort.

Experimental evidence shows that organophosphate esters (OPEs), common flame retardants and plasticizers, can cause developmental neurotoxicity. We investigated the extent to which prenatal OPE exposure was associated with child cognition. Participants were 831 mother-child pairs from 3 sites in the Environmental influences on Child Health Outcomes (ECHO) Cohort with data on urinary levels of 9 OPE analytes during gestation (2009-2019) and child cognition. Based on detection frequencies, analytes were modeled continuously (adjusted for urinary dilution and log2-transformed), categorically (high/low/non-detect), or dichotomously (detect/non-detect). Children's cognition was measured using the Wechsler Preschool and Primary Scale of Intelligence or Wechsler Intelligence Scale for Children at mean age 5.7 years (SD = 0.7). We examined associations of OPE analyte with age- and sex-standardized cognition scores using linear regression with generalized estimating equations to account for clustering within sites. We also tested for effect measure modification by sex. The analyte with the highest detection frequency (96.4 %) was diphenyl phosphate (DPHP), a primary metabolite of triphenyl phosphate (TPHP). Higher concentrations of DPHP were associated with lower cognition scores (βˆ per doubling of concentrations = -0.46, 95 %CI: -0.90, -0.02). Bis(butoxyethyl) phosphate (BBOEP), bis(1-chloro-2-propyl) phosphate (BCPP), and bis(2-methylphenyl) phosphate (BMPP) above the detection limit (vs. below) were associated with higher cognition scores mainly in boys; but, sex interaction with BMPP was not significant. Prenatal exposure to DPHP, a widely detected OPE, was associated with lower cognitive functioning, though the effect size was small. Given widespread exposure, findings related to this and other OPEs should be further examined in mechanistic studies.