Previously the main metabolites of di-n-butyl phthalate and diisobutyl phthalate, respectively, were inversely associated with child age 3 year motor development and increased the risk of motor delay. Among girls, MiBP was also inversely associated with mental development. Experimental animal studies find inverse associations between prenatal exposure to di-2- ethylhexyl phthalate and DnBP and learning and memory in the offspring. Tellez-Rojo et al evaluated prenatal phthalate exposure and repeated BSID scores at ages 2, 2.5 and 3 years in 135 children enrolled in the ELEMENT study in Mexico and found associations with DEHP metabolites in sex-specific analyses only. A final, albeit cross sectional, study found inverse associations between metabolites of DEHP and DnBP and vocabulary development at ages 8– 11 years among Korean children. The inconsistent associations regarding the specific phthalates may be due to the variability in age of assessment, the WISC testing different constructs than the BSID, poor adjustment for the correlations between phthalate metabolites, and differences in the concentrations of phthalates in the specific populations. Nevertheless, the consistent pattern of associations between MnBP and MiBP across ages in our cohort lends support to our cognitive findings. Comparison of the concentrations of phthalate metabolites in our study to those in the last reported NHANES data find, as expected, slightly higher concentrations among women in our sample. However, the confidence intervals in our data and the NHANES data overlap substantially, suggesting that the concentrations in our study are still relevant. There are several possible GW-572016 EGFR/HER2 inhibitor mechanisms underlying these associations. Phthalates may act as anti-androgens and lead to disruption in the normal sexual differentiation of the brain ; they may modulate the activity of aromatase in the developing brain and thus interfere with estrogen synthesis ; they may interfere with thyroid hormone production ; and they may disrupt brain dopaminergic activity which is linked to inattention and hyperactivity. These mechanisms may shed light on why the adverse associations are sex specific. Our study has a number of strengths. First it is a prospective evaluation with assessment of exposure to phthalates not only in the prenatal period, but also at ages 3 and 5 years. It is noteworthy that our associations were primarily limited to prenatal concentrations of phthalate metabolites, with some additional associations seen for age 3 exposures, suggesting that there are critical periods of exposure related to adverse cognitive outcomes. Second, although our sample size was likely not sufficient to estimate sex-specific associations, we did observe several sex specific differences in associations. This is important given that many of the purported mechanisms for these associations are linked to brain concentrations of sex hormones. However, there are also some limitations. We are unable to identify specific times during pregnancy when phthalates could be related to outcomes as urine was only collected from the pregnant women in the third trimester.