Gestational urinary BPA concentrations were associated with some neurobehavioral measures at 3 years of age in this cohort. In particular, gestational BPA exposure was associated with higher scores for measures of anxiety, hyperactivity, emotional control, and behavioral inhibition. Similar to our previous findings, the effects of gestational BPA exposure on these behavioral domains were larger among girls than boys.2
The different responses to gestational BPA exposure were especially pronounced for hyperactivity; girls exhibited increases in hyperactivity, and boys exhibited decreases in hyperactivity. In contrast, childhood urinary BPA concentrations were less important predictors of behavior or executive functions in this study.
The findings presented are consistent with numerous studies demonstrating altered neurobehavior among BPA-exposed animals.14,38
Gestational BPA exposures might affect endocrine or other neurotransmitter pathways and disrupt sexual differentiation of the brain, to alter behavior in a gender-dependent manner.39,40
However, the exposures and behavioral end points used in some animal studies might not be relevant or comparable to human cases.41
A recent epidemiological study suggests that gestational BPA exposure may be associated with impaired social behaviors in children.42
However, the authors did not find that their associations were modified by child gender.
The association of anxious, hyperactive, and depressive behaviors with gestational BPA exposure seems paradoxical at first; however, there is substantial comorbidity between attention-deficit/hyperactivity disorder, depression, and anxiety disorders.43
The pattern of observed associations suggests that gestational BPA exposure may affect neurobehavioral domains associated with behavioral regulation. Additional research using neuropsychologically based measures of these domains would enhance our understanding of BPA-neurobehavior relationships.
Our results suggested that girls in this cohort were more sensitive to gestational BPA exposures than were boys. This pattern should be interpreted cautiously, given the imprecision of the observed associations among girls and the low statistical power for interactions between gender and BPA exposures. This finding is intriguing, however, given the endocrine-disrupting nature of BPA. Future studies should examine other sexually dimorphic behaviors and should address whether boys and girls have different levels of susceptibility to BPA at different periods of development.
The results from analyses using the BRIEF-P corroborated our findings with the BASC-2 and suggest that associations between gestational BPA exposure and behavior might be related to poor behavioral regulation. Alternatively, this result might reflect the shared correlation between these 2 measures, rather than deficits in performance-based measures of executive function.25,44
The BRIEF-P may merely serve as an additional measure of problem behaviors.
The generalizability of our findings might vary according to predictors of neurobehavior and levels of BPA exposure in selected target populations. Consistent with findings in the United States, children from lower socioeconomic backgrounds had scores indicative of more behavioral and executive function impairment. Our observed urinary BPA concentrations were similar to those measured in other studies with pregnant women.3,45,46
Children's urinary BPA concentrations at 1, 2, and 3 years of age were higher than concentrations reported for adults but were slightly lower than concentrations observed among 6- to 11-year-old children in previous studies.47,48
Higher BPA concentrations in children could be attributable to pharmacokinetic factors or increased food consumption per unit of body mass.24
Accurate assessment of BPA exposure during the correct period of susceptibility is difficult. One of the primary strengths of this study is that we collected 6 spot urine samples from mothers and their children and averaged ≥2 urinary BPA concentrations during gestation or childhood, to reduce exposure variability. BPA concentrations in multiple spot urine samples still may exhibit substantial within-person variability but may classify BPA exposure accurately over time scales of days to weeks.22,47,49,50
With the assumption of nondifferential exposure misclassification, this error would result in null-biased estimates.51
Integrated exposure measures such as mean BPA concentrations might reduce misclassification rates, but they would decrease the ability to identify short time-sensitive windows of development. Future studies should consider the importance of collecting multiple or integrated urinary concentration measurements, to improve exposure classification during critical windows of neurodevelopment.
We adjusted for a variety of confounders, including factors that are difficult to measure, such as the caregiving environment and biomarkers of other environmental toxicants. Adjustment did not greatly affect the magnitude of most estimates, which suggests that confounding by these factors was not an important source of bias. However, additional, unidentified, confounding factors, including other hormonally active chemicals that vary with BPA or heritable personality traits that influence BPA exposure and childhood behavior, might explain some of the observed associations.
Our sample size was modest, which reduced our statistical power to test for gender modification and led to wide CIs. In addition, we examined many exposure-outcome associations, which increased the likelihood that our results might include the null value through chance alone. Instead of applying mathematical corrections for multiple comparisons, such as the Dunn-Bonferroni correction, we avoided strict application and interpretation of statistical significance thresholds (such as the 95% CI excluding the null value).52
Instead, we focused on the patterns, magnitudes, and consistency of our results and compared those factors with findings from our previous studies and experimental studies with animals.38,42
The clinical relevance of these findings is unclear at this point. Despite this uncertainty, clinicians can advise concerned patients to reduce their exposure, as well as cautioning that it is difficult to avoid all sources of exposure and the health consequences of BPA exposure are not fully understood. BPA exposure can be reduced by avoiding canned and packaged foods, receipts, and polycarbonate bottles with the recycling symbol 7.22,38,53,54