Maternal co-exposure to mercury and perfluoroalkyl acid isomers and their associations with child neurodevelopment in a Canadian birth cohort

Background: Perfluoroalkyl acids (PFAAs) within the broader class of per- and polyfluoroalkyl substances (PFAS) are present in human serum as isomer mixtures, but epidemiological studies have yet to address isomer-specific associations with child development and behavior. Objectives: To examine associations between prenatal exposure to 25 PFAAs, including perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) isomers, and child neurodevelopment among 490 mother–child pairs in a prospective Canadian birth cohort, the Alberta Pregnancy Outcomes and Nutrition (APrON) study. To consider the influence of a classic neurotoxicant, total mercury (THg), based on its likelihood of co-exposure with PFAAs from common dietary sources. Methods: Maternal blood samples were collected in the second trimester and child neurodevelopment was assessed at 2 years of age using the Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III). Linear or curvilinear multiple regression models were used to examine associations between exposures and neurodevelopment outcomes. Results: Select PFAAs were associated with lower Cognitive composite scores, including perfluoroheptanoate (PFHpA) (β = −0.88, 95% confidence interval (CI): −1.7, −0.06) and perfluorododecanoate (PFDoA) (β = −2.0, 95% CI: −3.9, −0.01). Non-linear relationships revealed associations of total PFOS (β = −4.4, 95% CI: −8.3, −0.43), and linear-PFOS (β = −4.0, 95% CI: −7.5, −0.57) and 1m-PFOS (β = −1.8, 95% CI: −3.3, −0.24) isomers with lower Language composite scores. Although there was no effect modification, including THg interaction terms in PFAA models revealed negative associations between perfluorononanoate (PFNA) and Motor (β = −3.3, 95% CI: −6.2, −0.33) and Social-Emotional (β = −3.0, 95% CI: −5.6, −0.40) composite scores. Discussion: These findings reinforce previous reports of adverse effects of maternal PFAA exposure during pregnancy on child neurodevelopment. The unique hazards posed from isomers of PFOS justify isomer-specific analysis in future studies. To control for possible confounding, mercury co-exposure may be considered in studies of PFAAs.