Sexually-Dimorphic Associations of Prenatal Phthalate Exposure and Neurobehavioral Development in 6-10 Year Olds

Abstract

Background: Concern has been raised over the potential neurobehavioral effects of prenatal phthalate exposure but available data are inconsistent. Aims: To examine associations between prenatal urinary concentrations of phthalate metabolites and neurobehavioral outcomes among children. Methods: We analyzed data on 153 children, aged 6 to 10 years, born to participants in the Study for Future Families, a multicenter pregnancy cohort study. Maternal urinary phthalate metabolite levels were measured during late pregnancy by high performance liquid chromatography-tandem mass spectrometry. Children were evaluated with the Child Behavior Checklist. With a useful re-parameterization of a standard regression interaction model, we estimated sex-specific associations between neurobehavioral outcomes and phthalate metabolites levels, adjusting for the child’s age, mother’s education, family stress, and urinary creatinine. Results: Concentration of monoisobutyl phthalate was associated in boys (but not girls) with inattention (b=0.27 (95% CI=0.04, 0.50)), rule-breaking behavior (b=0.20 (95% CI=0.01, 0.38)), aggression (b=0.34 (95% CI=0.09, 0.59)), and conduct problems (b=0.39 (95% CI=0.20, 0.58)). Among boys, the (molar) sum of di-2-ethylhexyl phthalate metabolites was associated with somatic problems (b=0.15, 95% CI=(0.03, 0.28), while in girls, it was negatively associated with anxiety problems (b=-0.21, 95% CI=-0.38, -0.04). Higher monobenzyl phthalate concentration was associated in boys with more oppositional behavior (b=0.16 (95% CI=0.01, 0.32)) and conduct problems (b=0.21 (95% CI=0.06, 0.37)), but with reduced anxiety in girls (b=-0.20, 95% CI=-0.39, -0.01). Higher monoethyl phthalate concentration was associated with fewer affective problems in boys (b=-0.12, 95% CI=-0.24, -0.01). Conclusions: Our results suggest associations between exposure to certain phthalates in late pregnancy and behavioral problems in boys.