Early life bisphenol A exposure and neurobehavior at 8years of age: Identifying windows of heightened vulnerability

Abstract

Background: Early life BPA exposure could affect neurobehavior, but few studies have investigated whether there are developmental periods when the fetus or child is more vulnerable to these potential effects.

Objectives: We explored windows of vulnerability to BPA exposure in a multiethnic cohort of 228 mothers and their children from Cincinnati, Ohio.

Methods: We measured urinary BPA concentrations at up to two prenatal and six postnatal time points from the 2nd trimester of pregnancy until the child was age 8years. At age 8years, we administered the Behavioral Assessment System for Children-2 (BASC-2), Behavior Rating Inventory of Executive Function, and Wechsler Intelligence Scale for Children-IV. We estimated covariate-adjusted differences in composite scores from each instrument using a multiple informant model designed to identify heightened windows of vulnerability.

Results: Among all children, there was not strong evidence that the associations between BPA and neurobehavior varied by the timing of exposure (Visit x BPA p-values≥0.16). However, child sex modified the associations of repeated BPA measures with BASC-2 scores (Visit x Sex x BPA p-values=0.02-0.23). For example, each 10-fold increase in prenatal BPA was associated with more externalizing behaviors in girls (β=6.2, 95% CI: 0.8, 11.6), but not boys (β=-0.8, 95% CI: -5.0, 3.4). In contrast, a 10-fold increase in 8-year BPA was associated with more externalizing behaviors in boys (β=3.9, 95% CI: 0.6, 7.2), but not girls (β=0.3, 95% CI: -3.5, 4.1).

Conclusions: We found that sex-dependent associations between BPA and child neurobehavior may depend on the timing of BPA exposure.

Keywords: Bisphenol A; Children; Epidemiology; Neurodevelopment.

Conflict of interest statement

Conflicts of Interest: The authors have no actual or potential competing financial interests.

Copyright © 2017 Elsevier Ltd. All rights reserved.

Figures

Figure 1

Adjusted differences in BASC-2 (row 1),1 BRIEF (row 2),1 and WISC-IV (rows 3–4)2 scores at 8 years of age with 10-fold increases in prenatal and childhood creatinine-standardized urinary BPA concentrations (Prenatal: N=202–210, Age 1: N=178–185, Age 2: N=159–165, Age 3: N=163–168, Age 4: N=131–132, Age 5: N=159–161, Age 8: N=200–204). 1Adjusted for: visit, BPA × visit, child’s sex, child’s race, mother’s education, household income, caregiving environment, marital status, prenatal serum cotinine concentrations, prenatal vitamins, mother’s BDI, and mother’s CAARS. 2Adjusted for: visit, BPA × visit, child’s sex, child’s race, mother’s education, household income, caregiving environment, marital status, prenatal serum cotinine concentrations, prenatal vitamins, and mother’s full-scale IQ. BPA × visit interaction term p-values were 0.18 for the global executive composite and 0.16 for the behavioral regulation index, indicating that these associations depended on the timing of BPA exposure. Heterogeneity p-values were >0.2 for all other outcomes. Exact sample sizes at each visit are available in Supplemental Table S3. Higher BASC-2 and BRIEF scores indicate worse behavior or executive function, while higher WISC-IV scores indicate better cognitive abilities. Abbreviations: Pre=Prenatal, BASC-2=Behavioral Assessment for Children-2, BRIEF=Behavior Rating Inventory of Executive Function, WISC-IV=Wechsler Intelligence Scale for Children-IV, BDI=Beck Depression Inventory, CAARS= Conners’ Adult ADHD Rating Scale

Figure 2

Adjusted1 difference in BASC-2,1 BRIEF,1 and WISC-IV2 IV scores at 8 years of age with 10-fold increases in prenatal and childhood creatinine-standardized urinary BPA concentrations, in girls (N=72–117) and boys (N=59–93). 1Adjusted for: visit, BPA × visit, child’s sex × visit, BPA × child’s sex, BPA × visit × child’s sex, child’s race, mother’s education, household income, caregiving environment, marital status, prenatal serum cotinine concentrations, prenatal vitamins, mother’s BDI, and mother’s CAARS. 2Adjusted for: visit, BPA × visit, child’s sex × visit, BPA × child’s sex, BPA × visit × child’s sex, child’s race, mother’s education, household income, caregiving environment, marital status, prenatal serum cotinine concentrations, prenatal vitamins, and mother’s full-scale IQ. BPA × visit × sex interaction term p-values were 0.05, 0.02, 0.23, and 0.17 for the BSI, EXT, INZ, and BRI, respectively, indicating differences in time windows of BPA exposure between girls and boys. Heterogeneity p-values were >0.2 for all other outcomes. Exact sample sizes at each visit are available in Supplemental Table S5. Higher BASC-2 and BRIEF scores indicate worse behavior or executive function, while higher WISC-IV scores indicate better cognitive abilities. Abbreviations: Pre=Prenatal, BASC-2=Behavioral Assessment for Children-2, BRIEF=Behavior Rating Inventory of Executive Function, WISC-IV=Wechsler Intelligence Scale for Children-IV, BSI=Behavioral Symptom Index, EXT=Externalizing Problems, INZ=Internalizing Problems, GEC=Global Executive Composite, BRI=Behavioral Regulation Index, MI=Metacognition Index, FSIQ=Full-Scale IQ, VCI=Verbal Comprehension Index, PRI=Perceptual Reasoning Index, PSI=Processing Speed Index, BDI=Beck Depression Inventory, CAARS= Conners’ Adult ADHD Rating Scale