Effects of Polybrominated Diphenyl Ethers on Child Cognitive, Behavioral, and Motor Development

Abstract

Polybrominated Diphenyl Ether (PBDE) flame retardants are environmental chemicals that cross the placenta during pregnancy and have shown evidence of neurotoxicity. As the in utero period is a sensitive developmental window, such exposure may result in adverse childhood outcomes. Associations between in utero PBDE exposure and neurodevelopment are found in animal models and increasingly in human population studies. Here, we review the epidemiological evidence of the association between prenatal exposure to PBDEs and motor, cognitive, and behavioral development in infants and children. Published work suggests a negative association between PBDE concentrations and neurodevelopment despite varying PBDE congeners measured, bio-specimen matrix used, timing of the biological sampling, geographic location of study population, specific developmental tests used, age of children at time of testing, and statistical methodologies. This review includes 16 published studies that measured PBDE exposure in maternal blood during pregnancy or in cord blood at delivery and performed validated motor, cognitive, and/or behavioral testing at one or more time during childhood. We evaluate possible mediation through PBDE-induced perturbations in thyroid function and effect measure modification by child sex. While the majority of studies support an adverse association between PBDEs and neurodevelopment, additional research is required to understand the mechanism of action, possibly through the perturbations in thyroid function either in the pregnant woman or in the child, and the role of biologically relevant effect modifiers such as sex.

Keywords: child behavior; child cognition; child motor development; child neurodevelopment; polybrominated diphenyl ethers (PBDEs); review.

Figure A1

Funnel Plot of Beta Coefficients associated with Wechsler Scales. 1. Points indicate effect sizes of PBDEs on Wechsler Scale domains (Total, Performance Intelligence, Verbal Comprehension, Perceptual Reasoning, Working Memory, and Processing Speed). Standard errors, when not reported in the study, were back-calculated from the 95% confidence intervals.

Figure 1

Selection process for systematic review.

Figure 2

PBDE concentrations of BDE-47, -99, -100, and -153 across cohorts. 1. Points represent PBDE concentration medians. Ranges represent 25th to 75th percentiles for World Trade Center (WTC), Health Outcomes and Measurements of the Environment Study (HOME), Center for the Health Assessment of Mothers and Children of Salina (CHAMACOS), and the Chinese (Laizhou Wan) cohort. Ranges represent minimum and maximum for the Taiwanese and Spanish (INMA) cohorts.

Figure 3

Associations between PBDEs and Bayley Scales coefficients and 95% confidence intervals across studies. 1. Points indicate beta coefficients (with 95% confidence intervals) for PBDE congeners’ association with Bayley Scale Mental Development Index at ages 1, 2, and 3 in the WTC and HOME cohorts. Age is noted in labels above. Negative coefficients indicate decreased neurocognitive functioning.

Figure 4

Associations between PBDEs and WISC scores and 95% confidence intervals across studies. 1. Points indicate beta coefficients (with 95% confidence intervals) for PBDE congeners’ association with Wechsler Score (Full Scale, Verbal, Performance, Working Memory, Perceptive Reasoning, and Processing Speed) at ages between 1 and 10.5 in the WTC, HOME, PELAGIE, and CHAMACOS cohorts. Age is noted in labels above. Negative coefficients indicate decreased neurocognitive functioning.

Figure 5

Associations between PBDEs and BASC scores and 95% confidence intervals across studies. 1 Points indicate beta coefficients (with 95% confidence intervals) for PBDE congeners’ association with Behavioral Assessment System for Children between ages 2 and 10.5 in the CHAMACOS and HOME cohorts. Age is noted in labels above. Positive coefficients indicate increased behavioral problems.

Figure 6

Hypothesized Directed Acyclic Graph of PBDE exposure and neurodevelopment. 1. DAG shows theoretical direct effect of PBDEs on child neurodevelopment, possibly mediated by maternal thyroid dysfunction, confounded by maternal SES, age, and IQ, and any possible “Z” confounders, and modified by child sex.