Paternal and maternal preconception urinary phthalate metabolite concentrations and child behavior

Background: Prenatal phthalate exposure has been associated with behavioral problems and lower performance on measures of cognitive ability in children. However, the potential effect of phthalate exposure during the sensitive preconception period is unknown. Objectives: To estimate the association of maternal and paternal preconception urinary phthalate metabolite concentrations with child behavior and evaluate potential modification by child sex. Methods: We used data from 166 children (111 singletons, 26 pairs of twins, and 1 set of triplets) born to 134 mothers and 100 fathers participating in a prospective preconception cohort study of subfertile couples from the Massachusetts General Hospital Fertility Center. We estimated mean maternal and paternal preconception exposures by averaging individual phthalate metabolite concentrations in multiple urine samples collected before pregnancy. We assessed children's behavior at 2-9 years of age by parent report using the Behavior Assessment System for Children-2 (BASC-2). We estimated the covariate-adjusted association between individual phthalate metabolite concentrations and the sum of di(2-ethylhexyl) phthalate metabolites (Sigma DEHP) and behavior scores, and evaluated differences in associations by child sex using linear regression with Generalized Estimating Equations. Models were further adjusted for prenatal phthalate concentrations in sensitivity analyses. Results: Each log(e)-unit increase in maternal and paternal preconception concentrations of Sigma DEHP was associated with a 2.0 (95% CI: - 3.2, - 0.7) and 1.8 (95% CI: - 3.1, - 0.4) point decrease in BASC-2 internalizing behavior scores among all children, respectively. We observed sex-specific associations for some phthalate biomarkers: among boys, maternal monoisobutyl phthalate (MiBP) was positively associated with externalizing behaviors, and paternal MiBP and mono-n-butyl phthalate were positively associated with internalizing behaviors. Conclusions: In this cohort, paternal and maternal preconception concentrations of some phthalate biomarkers were associated with specific aspects of child behavior, even after adjustment for prenatal concentrations. While additional research is warranted to confirm these results, our findings suggest that the preconception period of exposure may be a critical window for offspring neurodevelopment.