This is the first study to examine the association between prenatal BPA exposure and childhood behavior. We did not observe an association between mean urinary BPA concentrations and behavior scores among all children. However, we report an association between mean prenatal BPA concentrations and externalizing scores in females. Further examination revealed that the association between prenatal BPA concentrations and externalizing behaviors in 2-year-old girls was driven by maternal urine BPA concentrations measured at 16 weeks of gestation. The association between early BPA concentrations and externalizing scores was strongest among women with urine measurements taken at ≤ 16 weeks of gestation. The interaction between sex and 16-week BPA concentrations persisted in samples taken at ≤ 16 weeks of gestation.
We observed an inverted U-shaped association between maternal urinary BPA concentrations and internalizing behaviors among male children in our sample. Others have written extensively about the possibility of a nonlinear dose–response curve between environmental estrogens and various end points (Welshons et al. 2003
Two issues must be considered when comparing the results of our study to those of rodent studies. First, the route of exposure in animal studies has included oral, subcutaneous, and direct injection at target organs (Li et al. 2008
), whereas humans are exposed predominantly through the oral route (Chapin et al. 2008
). Second, animal studies have used doses spanning several orders of magnitude, many of which are not relevant to human exposure (Li et al. 2008
Prenatal urinary BPA concentrations among women in this study were similar to those from women of childbearing age from a nationally representative U.S. sample (Calafat et al. 2008
), from a previous study examining the association between BPA exposure and infant birth outcomes among minority pregnant women in New York City (Wolff et al. 2008
), and from pregnant women in Rotterdam, the Netherlands (Ye et al. 2008
This study has several limitations. First, the children in our sample were 2 years of age at the time of behavioral assessment. Patterns of behavior are variable during early childhood. However, longitudinal analyses of children reveal that inattentive/hyperactive behaviors tend to be stable over childhood, whereas aggressive behaviors decrease (Jester et al. 2005
; Nagin and Tremblay 2001
; Tremblay et al. 2004
). Second, unmeasured confounding may be responsible for some or all of our observed associations. Mink et al. (2004)
have shown that unmeasured confounding can be responsible for much of the observed association between environmental neurotoxicants and neurobehavioral function. Although we included many of the same confounders used in studies of other neurotoxicants, it is possible that we did not adequately assess parental psychopathology (e.g., parental attention deficit/hyperactivity disorder). Third, there is evidence that prenatal BPA exposure disrupts normal mother–child interactions in rodent models (Palanza et al. 2008
). Female mice exposed to BPA spend less time in their nest and nursing their offspring and more time grooming and resting alone. Therefore, associations between childhood behavior and prenatal BPA exposure may be mediated through maternal behavior toward the child. Finally, maternal BPA measurements taken at 26 weeks and birth may be influenced by the glucose tolerance test and birthing process, respectively. However, this is unlikely because creatinine-adjusted BPA concentration distributions were almost identical at each time point. We would have expected BPA concentrations to be higher at birth because women would be more likely to be exposed to BPA containing plastics, such as intravenous tubing, in the hospital setting (Calafat et al. 2009
). The lack of a difference could be attributable to increased plasma volume from intravenous fluids, hospital diet or fasting near delivery, metabolic changes from the birthing process, hospital policies that limit BPA-containing plastics, or a combination of all of these factors.
Exposure misspecification may be responsible for our observed results. This could bias our results toward or away from the null, depending on the nature of the misspecification and characterization of the exposure (continuous vs. categorical). BPA has a short half-life in biological tissues (Volkel et al. 2002
), although a recent analysis of the 2003–2004 National Health and Nutrition Examination Survey suggests that BPA may have a longer than expected half-life (Stahlhut et al. 2009
). Urinary BPA concentrations have a moderate degree of intraindividual variability, making it difficult to accurately characterize exposure from a single measurement. The lack of prior literature on the appropriate specification of BPA exposure during pregnancy makes it difficult to determine if a single measurement or summary measurement of BPA concentration more accurately quantifies exposure. Because women did not have repeated urine measurements around 16 weeks of gestation, we assumed that timing of the 16-week urine measurement was random. The results of these analyses should be interpreted cautiously because this assumption may not be true. As recommended previously by Wolff et al. (2008)
, additional research into characterizing BPA exposure is necessary. An additional source of exposure misspecification may have arisen from BPA degradation in samples that were stored for > 3 years. However, prior work indicates that storing urine samples at subfreezing temperatures for as long as 30 months does not result in substantial loss of BPA (Calafat et al. 2009
Another limitation is that we were not able to examine whether postnatal BPA exposure was associated with childhood behavior. We are planning to examine this association in future studies of this cohort.
Selection bias is another potential limitation of our study because women were required to be living in pre-1978 housing. It is possible that children living in older housing stock come from lower socioeconomic status, making them more likely to have behavior problems. However, this is unlikely because families in our sample have higher levels of education and income than the general population.
Finally, there were two statistical limitations to this study. First, it could be argued that our observed associations are spurious because of the large number of associations we examined. However, multiple comparison arguments assume that randomness underlies the variability of all the observed associations (Rothman 1990
; Savitz and Olshan 1995
). It is unlikely that our results are attributable to random variation because we observed a consistent association between prenatal urinary BPA concentrations and externalizing behaviors in females that became stronger in measurements taken earlier in pregnancy. Second, our power to detect associations between maternal BPA exposure and childhood behavior was diminished in our analyses examining sex- and time-specific associations, resulting in imprecise estimates.
This study has several strengths. First, we had three urinary BPA measurements in the latter two-thirds of pregnancy to estimate gestational exposure. This allowed us to examine whether some periods of gestation are sensitive to BPA exposure. Second, we used a valid and reliable measure of adaptive and problem behaviors in children (Kamphaus et al. 1999
). Finally, we are continuing to follow these children through 5 years of age, which will allow us to examine whether our observed associations persist throughout early childhood.
Mean prenatal BPA concentrations were not associated with childhood behavior. However, we did observe a positive association between these concentrations and externalizing behaviors among females. Early second-trimester maternal urinary BPA concentrations were positively associated with externalizing behaviors and global behavior scores among all children, but especially among 2-year-old female children. Our results suggest that BPA concentrations in samples taken earlier in pregnancy may be more strongly associated with externalizing scores than those in later samples. The reported associations and interactions between child sex and timing of BPA exposure should be viewed cautiously because these results could be biased by exposure misspecification or residual confounding. Future research should aim to develop methods to accurately characterize BPA exposure, especially during the first trimester of pregnancy; to validate the associations observed in this cohort; and to examine the association between pre- and postnatal BPA exposure and behavior in later childhood.