Association of placental concentrations of phenolic endocrine disrupting chemicals with cognitive functioning in preschool children from the Environment and Childhood (INMA) Project

Developmental exposure to bisphenol A (BPA) and other phenolic endocrine disrupting chemicals (EDCs) may affect child neurodevelopment, but data on the effects of prenatal exposure to phenols on cognitive function remain sparse. Our aim was to examine the association of placental concentrations of several phenolic EDCs, including BPA, parabens (PBs), and benzophenones (BzPs), with cognitive development in preschool children from the Environment and Childhood (INMA) Project in Spain. Concentrations of BPA, four PBs (methylparaben [MePB], ethylparaben [EtPB], propylparaben [PrPB], and butylparaben [BuPB]), and six BzPs (BzP-1, BzP-2, BzP-3, BzP-6, BzP-8, and 4-hydroxybenzophenone [4-OH-BzP]) were measured in 490 placenta samples randomly selected from five INMA cohorts collected between 2000 and 2008. Neuropsychological assessment of cognitive and motor function was performed with the McCarthy Scales of Children's Abilities (MSCA) at the age of 4-5 years. Associations were assessed in a sub-sample of 191 mother-child pairs using linear and logistic regression models adjusted for confounding factors. PB compounds were detected in more than 71% of placentas, BPA in 62%, 4-OH-BzP in 50%, and the remaining BzPs in <9% of the samples. Because of the low detection frequency of BzP compounds, only 4-OH-BzP was included in the exposure-outcome analyses. After adjustment for confounders, BPA was associated with greater odds of scoring lower (below the 20th percentile) in the verbal (third vs. first exposure tertile: odds ratio [OR] = 2.78, 95% confidence interval [CI] = 1.00; 5.81, p-trend = 0.05) and gross motor (detected vs. undetected: OR = 1.75, 95%CI = 1.06; 9.29) areas, and these associations were only significant for boys. Regarding PB compounds, PrPB was associated with lower scores in memory (detected vs. undetected: β = -4.96, 95%CI = -9.54; -0.31), span memory (OR = 2.50, 95%CI = 0.95; 6.92 and 2.71, 95%CI = 0.97; 6.64, respectively for second and third tertiles, p-trend = 0.03), and motor function (β = -5.15, 95%CI = -9.26; -0.01 for third vs. first exposure tertile, p-trend = 0.04). EtPB and total PBs concentrations in the second tertile were also associated with poorer visual function of posterior cortex and worse quantitative performance, respectively, but linear trends were not statistically significant. The associations of BPA and PrPB with poorer verbal, memory, and motor skills are novel observations that warrant further attention. Larger prospective studies are required to confirm whether prenatal exposure to BPA and other phenolic EDCs is associated with impaired cognitive development.