In this cohort of children born to mothers residing adjacent to a PCB-contaminated harbor, prenatal umbilical cord blood PCB levels were low relative to other population-based PCB studies (13
). Despite low exposure levels, we detected moderate associations between PCB and p
′-DDE levels and ADHD-like behaviors in this population.
Previous studies of PCBs and child behavior have largely focused on psychometric test batteries for which associations with clinical ADHD have not been established. Neuropsychological test batteries were not used in this analysis and may measure something different than behaviors observed by a child's teacher; however, our findings are broadly consistent with PCB-associated increases in inattention and impulsive responding observed with psychometric testing. For example, associations between prenatal PCB exposure and increased reaction time were found in the Faroe Islands (4
) (in the presence of high mercury exposure) using the Neuropsychological Evaluation System Continuous Performance Test at age 7 years and in Dutch children (11
) using the Simple Reaction Time Test at age 9 years, suggesting a possible impact on attention. Studies of Michigan children born to consumers of PCB-contaminated fish found no association between prenatal PCB exposures and sustained attention (defined as the ability to maintain focus and alertness over time), measured with a continuous performance test at ages 4 and 11 years (6
), but did find an association with focused attention (defined as the maintenance of attention in the presence of distractions), using a digit cancellation task (6
) and the freedom-from-distractibility scale of the Wechsler Intelligence Scale for Children at age 11 years (5
). Investigators from the Oswego Newborn and Infant Development Project reported associations between prenatal PCBs and errors of commission (false-positive responses) on the Continuous Performance Test at 4.5, 8, and 9.5 years of age, suggesting a potential impairment of response inhibition (9
). This was supported by observed associations of PCBs with poorer performance on the Differential Reinforcement of Low Rates of Response test (in the same cohort at age 9.5 years), which measures the ability to withhold a rewarded response for a specific time delay, another test of response inhibition (22
In addition, we recently reported associations between prenatal PCB and p
′-DDE exposures and poor attention in early infancy in the New Bedford cohort using items selected a priori from the Neonatal Behavioral Assessment Scale, including alertness, quality of alert responsiveness, and cost of attention (8
In the only study of the association between PCBs and clinically diagnosed ADHD, Lee et al. (23
) reported null findings. However, that study, which used data from the National Health and Nutrition Examination Survey, had a number of limitations (24
): Firstly, PCB exposure assessment was confined to only 1 PCB congener (PCB 126) which is coplanar, present at extremely low levels (parts per trillion) in population samples, and not representative of the likely toxic mechanism of the more prevalent non-dioxin-like and mono-ortho PCBs found in most population-based samples. For PCBs, it has been postulated that the non-dioxin-like congeners may be the ones that are more deleterious to neurocognitive functions (25
). Secondly, the design was cross-sectional; therefore, Lee et al. were unable to evaluate the effect of prenatal organochlorine exposure, which may be the most critical exposure period. Thirdly, ADHD diagnosis was based on parental reports, the validity of which is unclear.
In animal studies, investigators have reported associations between PCBs and ADHD-like behaviors in rodents and nonhuman primates (27
), and laboratory studies show that PCBs can disrupt dopamine levels and dopaminergic function in the brain (30
); dopamine system dysfunction has also been linked with ADHD (32
). Organochlorines, including PCBs, have also been shown to reduce circulating levels of thyroid hormones in animals (33
) and humans (34
). Associations between these hormone disruptions and ADHD-like behaviors have been demonstrated (36
), though not consistently (39
This analysis focused on ADHD-associated behaviors assessed with a teacher's behavioral rating scale, rather than clinically diagnosed ADHD. Although behavioral checklists like the CRS-T may not be associated with clinical ADHD on an individual basis, they are used in conjunction with other guidelines for clinically diagnosing this disorder and characterizing the functional consequences of its symptoms (inattention, hyperactivity, impulsivity). The CRS-T assesses ADHD-like behaviors on a continuous scale—a strength of this study, since ADHD may be best viewed on a behavioral continuum rather than as a categorical disorder (41
). Assessing continuously distributed outcomes rather than clinical diagnoses, in addition to improving power, also prevents classification to a diagnosis with a potentially arbitrary cutoff or subjective guidelines that may change over time (42
). In addition, deficits on neurobehavioral examinations may indicate early stages of a disorder or more mild cases of this disorder, which a clinical diagnosis would tend to miss (42
Though the observed associations between organochlorines and continuous CRS-T outcomes were modest (e.g., a 2.4-point increase in the Conners’ ADHD Index for a 0.6-ng/g increase in the sum of 4 PCBs ()), a shift in group mean is less important for its average change in the population and more important for the change represented at the tails of the distribution, where clinical disease is detected (42
). Thus, even a small association between prenatal organochlorines and a health indicator such as increased ADHD-associated behavior in childhood can signal substantial changes in the prevalence of clinically evident ADHD in the population. In fact, with dichotomized CRS-T measures, children in the upper 75% of exposure (ΣPCB4
ranging from 0.30 ng/g to 4.4 ng/g) had a substantially increased risk (risk ratio = 1.8, 95% confidence interval: 1.1, 2.9) of possible or significant behavioral problems on the Conners’ ADHD Index ().
Covariate data were missing for a notable proportion of study subjects (10%–15% of those with exposure and outcome data). While this probably reduced the precision of our estimates, we ruled out selection bias by showing that the association between PCBs and ADHD-like behaviors was not meaningfully different for the subsets with and without complete covariate data (). In addition, imputing covariate data did not change our findings (data not shown).
Notably, in our population higher age was associated with higher risk of ADHD-like behaviors. High-risk children may have been more difficult to schedule or follow up, which could explain why they were examined at older ages.
We found evidence for negative confounding by covariates in the associations between organochlorines and ADHD-like behaviors, as shown by stronger adjusted exposure-outcome estimates than unadjusted estimates (). Residual confounding due to incomplete adjustment for negative confounders would potentially lead to underestimation of the true exposure-outcome association.
In summary, associations between prenatal exposure to organochlorines, including PCBs and p,p′-DDE, and ADHD-like behaviors were found using a teacher-administered rating scale. Given the burden these behaviors place on the medical and educational system and on the family, identification of modifiable risk factors is a public health priority. Future work in the New Bedford cohort will be directed toward finding consistency between these results and those obtained using other neurobehavioral tests.