Developmental PBDE Exposure and IQ/ADHD in Childhood: A Systematic Review and Meta-analysis

Abstract

Background: In the United States, one in six children are affected by neurodevelopmental disorders, and polybrominated diphenyl ethers (PBDEs) in flame-retardant chemicals are measured ubiquitously in children.

Objective: We conducted a systematic a systematic review regarding developmental exposure to PBDEs and intelligence or Attention Deficit/Hyperactivity Disorder (ADHD) and attention-related behavioral conditions in humans.

Methods: We searched articles published up to 26 September 2016, and included original studies that quantified exposures to PBDEs incurred any time in proximity to conception or during in utero, perinatal, or childhood time periods. We evaluated the risk of bias of individual studies and the overall quality and strength of the evidence according to the Navigation Guide systematic review methodology. We established criteria in advance to identify studies that could be combined using random effects meta-analyses (DerSimonian-Laird method).

Results: Fifteen studies met the inclusion criteria; 10 studies met the criteria for intelligence and nine for attention-related problems. We rated studies generally with "low" to "probably low" risk of bias and rated the overall body of evidence as "moderate" quality with "sufficient" evidence for an association between Intelligence Quotient (IQ) and PBDEs. Our meta-analysis of four studies estimated a 10-fold increase (in other words, times 10) in PBDE exposure associated with a decrement of 3.70 IQ points (95% confidence interval: 0.83, 6.56). We concluded the body of evidence was of "moderate" quality for ADHD with "limited" evidence for an association with PBDEs, based on the heterogeneity of association estimates reported by a small number of studies and the fact that chance, bias, and confounding could not be ruled out with reasonable confidence.

Conclusion: We concluded there was sufficient evidence supporting an association between developmental PBDE exposure and reduced IQ. Preventing developmental exposure to PBDEs could help prevent loss of human intelligence. https://doi.org/10.1289/EHP1632.

Figure 1.

Flowchart showing the literature search and screening process for studies relevant to PBDE exposure and IQ/ADHD outcomes. The primary goal of our search was to obtain comprehensive results; therefore, our search was not limited by language or publication date. The search terms used for each database are provided in Table S1.

Figure 2.

Summary of risk of bias judgments (low, probably low, probably high, high) for the human studies included in our systematic review of PBDE exposure and a) IQ or b) ADHD outcome. Risk of bias designations for individual studies are assigned according to criteria provided in Supplemental Material, “Instructions for Making Risk of Bias Determinations” and the justification for each study is provided in Tables S4–S18.

Figure 3.

Meta-analysis of human studies ($n=4$ studies, 595 children) for PBDE exposure (represented as congener BDE-47, lipid-adjusted) measured in cord blood or maternal serum during gestation or at birth for IQ outcome (FSIQ or McCarthy Scale) assessed in children between 48–84 months: reported effect estimates [95% confidence interval (CI)] from individual studies (inverse-variance weighted, represented by size of rectangle) and overall pooled estimate from random effects (RE) model per 10-fold increase (in other words, times 10) in PBDE exposure. Heterogeneity statistics: Cochran’s $Q=0.1367$; $p=0.99$; $I^2=0\%$. Estimates were adjusted as follows: Herbstman et al. 2010: age at testing, race/ethnicity, IQ of mother, sex of child, gestational age at birth, maternal age, environmental tobacco smoke exposure, maternal education, material hardship, breastfeeding, language and location of interview; Gascon et al. 2011: sex, age of the child, preterm, evaluating psychologist, maternal age, social class, education, parity, smoking during pregnancy, alcohol consumption, prepregnancy BMI; Eskenazi et al. 2013: child’s age, sex, HOME score at 6-months visit, language of assessment, and maternal years living in United States before giving birth; Chen et al. 2014: maternal age at enrollment, race, education, marital status, maternal serum cotinine concentrations at enrollment, maternal IQ, child sex, maternal depression, household income, and HOME (Home Observation for Measurement of the Environment) inventory.