Early Life Phthalate Exposure and Cognition at Age 8 Years: Identifying Windows of Heightened Vulnerability

Abstract

Background: Early-life phthalate exposures may adversely affect children’s neurodevelopment by disrupting thyroid function, reducing gonadal hormone levels, or altering concentrations of fatty acids in the brain. We attempted to identify windows of heightened vulnerability to phthalate exposures during fetal period and early childhood.Methods: We used data from 204 mother-child pairs in the HOME Study (Cincinnati, Ohio), a longitudinal pregnancy-birth cohort. We quantified phthalate biomarkers in urine samples collected up to twice at gestational visits and up to 6 times during childhood visits at ages 1-8 years. We assessed children’s intelligence (IQ) at age 8 years using the Wechsler Intelligence Scale for Children-IV. We estimated covariate-adjusted associations between log10-transformed biomarker concentrations and children’s IQ at each visit, and tested for differences in these associations across visits using multiple informants models.Results: The associations between phthalate biomarker concentrations and IQ varied by visit (biomarker*visit interaction p-values<0.2). Concentrations of monobenzyl phthalate, mono(3-carboxypropyl) phthalate, and monoethyl phthalate at ages 2 and 3 years, and di(2-ethylhexyl) phthalate (ΣDEHP) metabolites at age 3 years were inversely associated with children’s full-scale IQ. For example, each 10-fold increase in urine ΣDEHP concentrations at age 3 was associated with a 4.9-point decrease in full-scale IQ (95% confidence interval [CI]: -8.8, -1.1). Concentrations of mono-n-butyl phthalate (MnBP) at age 4 years and mono-isobutyl phthalate at gestation and age 4 years were positively associated with children’s IQ. For instance, each 10-fold increase in urine MnBP concentrations at age 4 years was associated with a 5.0-point increase in full-scale IQ (95% CI: 0.8, 9.2).Conclusion: In this cohort, associations of gestational and childhood urinary phthalate biomarker concentrations with IQ scores depended on the timing of exposure.