Evaluation of integrated, multimedia biomarkers of prenatal metals exposure in association with child neurodevelopment in Puerto Rico.

Résumé

BACKGROUND: Biomarkers can be measured in various media, including urine or blood, which represent different biological compartments and toxicokinetic pathways, resulting in potential biases when estimating the internal dose of an environmental exposure. Integrating measurements across multiple media as a multimedia biomarker (MMB) may better characterize an exposure, allowing for improved assessment of exposure-outcome relationships.OBJECTIVE: This study utilized concentrations of 10 metals in urine, blood, and as MMBs, integrated using intraclass correlation coefficients (MMB) and weighted quantile sum regression (MBB), to investigate associations with child neurodevelopment, using the Child Behavior Checklist (CBCL).METHODS: We examined log-transformed geometric mean prenatal metal concentrations (in urine, blood, or as MMBs) in association with repeatedly measured CBCL scores for ages 1.5-5 years, in 284 mother-child pairs in the PROTECT birth cohort in Puerto Rico. Summary scores were modeled as log(CBCL + 1). Associations were assessed as single-pollutants and as a mixture, using linear mixed-effects models, adaptive elastic net, and Bayesian kernel machine regression, adjusted for sex, maternal education level, maternal age, and child age at assessment.RESULTS: In single-pollutant models, prenatal urinary As and Co; blood Cd and Mn; MMB Cd and Co; and MMB Cd, Co, and Mn were associated with higher emotional and behavioral problems in children. For example, Cd was associated with 0.24 (0.08, 0.41) higher CBCL total problem scores per interquartile range (IQR) increase in blood, 0.19 (0.07, 0.31) in MMB, and 0.19 (0.06, 0.31) in MMB (all p