Sex-specific associations between maternal phthalate exposure and neurodevelopmental outcomes in children at 2 years of age in the APrON cohort

There is inconsistent evidence regarding the sex-specific associations between prenatal phthalate exposure and children’s neurodevelopment. This could be due to differences in the phthalate exposures investigated and the neurodevelopmental domains assessed. To evaluate the associations between prenatal phthalate exposure and sex-specific outcomes on measures of cognition, language, motor, executive function, and behaviour in children 2 years of age in the Alberta Pregnancy Outcomes and Nutrition (APrON) cohort. We evaluated the associations between prenatal phthalate exposure and sex-specific neurodevelopmental outcomes in children at 2 years of age using data from 448 mothers and their children (222 girls, 226 boys). Nine phthalate metabolites were measured in maternal urine collected in the second trimester of pregnancy. Children’s cognitive, language, and motor outcomes were assessed using the Bayley Scales of Infant Development – Third Edition (Bayley-III). Parents completed questionnaires on children’s executive function and behavior, the Behavior Rating Inventory of Executive Function- Preschool Version (BRIEF-P) and Child Behavior Checklist (CBCL), respectively. Sex-stratified robust multivariate regressions were performed. Higher maternal concentrations of ΣDEHP and its metabolites were associated with lower scores on the Bayley-III Cognitive (β’s from −11.8 to −0.07 95% CI’s from −21.3 to −0.01), Language (β’s from −11.7 to −0. 09, 95% CI’s from −22.3 to −0.02) and Motor (β’s from −10.9 to −0.07, 95% CI from −20.4 to -0.01) composites in boys. The patterns of association in girls were in the opposite direction on the Cognitive and Language composites; on the Motor composite they were in the same direction as boys, but of reduced strength. Higher concentrations of ΣDEHP and its metabolites were associated with higher scores (i.e., more difficulties) on all measures of executive function in girls: inhibitory self-control (B’s from 0.05 to 0.11, 95% CI s from −0.01 to 0.15), flexibility (B’s from 0.04 to 0.11, 95% CI s from 0.01 to 0.21) and emergent metacognition (B’s from −0.01 to 0.06, 95% CIs from −0.01 to 0.20). Similar patterns of attenuated associations were seen in boys. Higher concentrations of ΣDEHP and its metabolites were associated with more Externalizing Problems in girls and boys (B’s from 0.03 to 6.82, 95% CIs from −0.08 to 12.0). Two phthalates, MMP and MBP, had sex-specific adverse associations on measures of executive function and