Prenatal exposure to a mixture of organochlorines and metals and internalizing symptoms in childhood and adolescence

Background: Although prenatal chemical exposures influence neurobehavior, joint exposures are not well explored as risk factors for internalizing disorders through adolescence. Objective: To evaluate associations of prenatal organochlorine and metal exposures, considered individually and as a mixture, with mid-childhood and adolescent internalizing symptoms. Methods: Participants were 468 children from a prospective cohort recruited at birth (1993-1998) in New Bedford, Massachusetts. Organochlorines (hexachlombenzene, p,p'-dichlorodiphenyl dichlomethylene, polychlorinated biphenyls) and metals (lead, manganese) were analyzed in cord blood. Internalizing symptoms (anxiety, depressive, somatic) were assessed via multiple informants on the Conners' Rating Scale (CRS) at 8-years and Behavior Assessment System for Children, Second Edition (BASC-2) at 15-years; higher T-scores indicate greater symptoms. Overall and sex-specific covariate-adjusted associations were evaluated using Bayesian Kernel Machine Regression (BKMR) and five-chemical linear regression models. Results: The cohort was socioeconomically diverse (35% household income <$20,000; 55% maternal <= high school education at birth). Most chemical concentrations were consistent with background levels [e.g., median (range) cord blood lead: 1.1 (0-9.4) mu g/dL]. BKMR suggested linear associations and no interactions between chemicals. The overall mixture was positively associated with Conners' Parent Rating Scale (CPRS) and BASC-2 Self Report of Personality (SRP) anxiety and depressive symptoms, and negatively with somatic symptoms. Prenatal lead was positively associated with adolescent anxiety symptoms [1.56 (95% CI: 0.50, 2.61) BASC-2 SRP Anxiety score increase per doubling lead]. For CRPS and BASC-2 SRP, a doubling of cord blood manganese was positively associated with internalizing symptoms for girls [e.g., 3.26 (95% CI: 0.27, 6.25) BASC-2 SRP Depression score increase], but not boys. Organochlorine exposures were not adversely associated with internalizing symptoms. Discussion: Low-level prenatal lead exposure was positively associated with adolescent anxiety symptoms, and prenatal manganese exposure was positively associated with internalizing symptoms for girls from mid- childhood through adolescence. In utero neurotoxicant metal exposures may contribute to the emergence of anxiety and depression.