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

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_ICC) and weighted quantile sum regression (MBB_WQS), 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_ICC Cd and Co; and MMB_WQS 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_ICC, and 0.19 (0.06, 0.31) in MMB_WQS (all p < 0.05; q < 0.1 for blood and MMB_WQS). The effects of the cumulative mixture of MMB metals were not consistently more strongly associated with CBCL scores compared to blood media.

Significance

The results of this study can inform future research on optimizing biomarker assessment and reducing measurement error to assess the effect of metal mixtures on child neurodevelopment.

Impact statement

Combining multiple biomarker media may better capture health effects compared to single-media biomarker analyses, especially for the effects of exposure to metals with varied toxicokinetic properties. Our findings provide insight to potential approaches for combining blood and urine biomarkers and to the selection of preferred media for toxic and essential metals, with the goal of reducing measurement error and accounting for toxicokinetics. Future research should explore the integration of other commonly utilized biomarkers to compare their performance and efficacy as integrated MMBs in larger sample sizes.