Prenatal urinary biomarkers of metal and metalloid exposure and child neurodevelopmental outcomes in Puerto Rico

Exposure to toxic metals, and insufficient or excess levels of essential metals, particularly during sensitive stages of development, can pose health risks. Previous research reports that prenatal exposure to metal mixtures is associated with poorer cognitive and behavioral outcomes. However, little research has studied the impact of prenatal exposure to complex metal mixtures on child behavioral and emotional development specifically in Puerto Rico, a population with exposure and health disparities. This study aims to understand how prenatal exposure to 14 metals affects child neurodevelopment using the Child Behavior Checklist (CBCL) at 1.5, 2, 3, 4, and 5 years. We examined associations between urinary prenatal metal concentrations, collected at 18 ± 2, 22 ± 2, and 26 ± 2 weeks of gestation, and repeated CBCL raw scores in 301 mother-child pairs from the PROTECT birth cohort in Northern Puerto Rico. The median raw CBCL total problem score was 19. In single-pollutant linear mixed-effects models, As, Co, and Sn were significantly associated with higher internalizing and total problem scores, indicating more parent-reported emotional and behavioral problems. An interquartile range increase in ln(Sn) was associated with a 0.17 (95 % CI: 0.05, 0.29) point higher ln(Total Problems + 1) score. As exposure was associated with higher CBCL problem scores for male children across all domains, while Cu was associated with higher externalizing problems among females. In mixture analyses using adaptive elastic net and Bayesian kernel machine regression, Co, As, and Sn predominantly contributed to higher CBCL scores, specifically among male children. However, there were mostly only additive interactions between metals. These results elucidate the effects of multiple metals on behavioral and emotional development.