Major characteristics of the 587 cohort members contributing serum samples at ages 5 and/or 7 years are included in . The pre-booster concentration of both diphtheria and tetanus antibodies correlated well with the results at the two subsequent examinations (). Similarly, correlations between log-transformed tetanus and diphtheria concentrations obtained at the same examination were 0.45, 0.32, and 0.43 at the three occasions (before booster, 1 month after booster, and at 7 years, respectively). Although boys had higher antibody concentrations than girls and also had higher PCB exposures at ages 5 and 7 years (results not shown), the extended set of covariates appeared to cause little potential for confounding.
Characteristics, with arithmetic mean ± SD and geometric mean (interquartile range) values, of 587 birth cohort members examined for serum concentrations of specific vaccine antibodies at ages 5 and 7 years.
Geometric mean (and interquartile range) serum antibody concentrations (IU/L) in 587 children examined on up to three occasions at ages 5–7 years.
Results of multiple regression analyses with adjustment for sex and age indicated a clear inverse association between the pre-booster diphtheria-specific antibody concentration and PCB concentrations in maternal milk and in the child’s serum at 18 months of age, although the latter comparison was based on a much smaller number of subjects than the other comparisons. PCB levels measured at age 5 years were not associated with the pre-booster tetanus response at this age (). Further adjustment for additional covariates did not materially affect these results.
Relative change in serum antibody concentrations at age 5 years (before booster vaccination) associated with a doubling in developmental exposure to PCBs, as indicated by the concentrations in biological samples obtained at different times.
Serum antibody concentrations after the 5-year booster vaccination varied according to the time interval between the booster vaccination and serum collection (). Five children had a negative interval (i.e., they were examined before the booster vaccination) and were therefore excluded from the analysis of post-booster antibody concentrations. A cubic spline function was used for adjustment of the data used in these regression analyses. Each of the two newer booster vaccinations that included additional vaccines were associated with lower antibody responses for both tetanus and diphtheria (p < 0.05); adjustment for the booster type was therefore also included in these models as well as for the 7-year data.
Figure 1 Time-dependent change in serum antibody concentrations against tetanus and diphtheria in 455 Faroese children after booster vaccination at age 5 years, as modeled by a cubic spline function adjusted for sex, age, and booster type. Results are shown for (more ...)
Although none of the PCB concentrations at different time points reached statistical significance as predictors at the post-booster examination, all showed an inverse association with the antibody concentrations. Thus, doubling of PCB concentrations in maternal serum [−7.5%; 95% confidence interval (CI), −18.8 to 5.4; p = 0.24], milk (−8.2%; 95% CI, −16.9 to 1.5; p = 0.10) and 18-month serum (−8.3%; 95% CI, −26.4 to 14.2; p = 0.43) suggested similar relative declines in the diphtheria antibody concentration. Although inclusion of the additional covariates did not materially affect these results, the concurrent 5-year serum PCB concentration became a significant predictor (−11.6%; 95% CI, −19.4 to −3.0; p = 0.01) for the diphtheria antibody concentration after adjustment for all covariates.
At age 7 years, six children were excluded because they had received an additional booster at some point after the routine booster at 5 years of age. Children inoculated with the two combination vaccines containing pertussis and/or polio showed a lower antibody response toward tetanus and diphtheria, and combination booster was therefore included as a covariate along with sex and age. Again, we saw inverse associations with PCB exposure, although not as strong as at age 5 years (). Only the serum PCB concentration at age 18 months approached statistical significance with regard to the decrease in diphtheria antibody concentrations, although the response was almost as strong with regard to tetanus.
Table 4 Relative change in serum antibody concentrations at age 7 years associated with a doubling in developmental exposure to PCBs, as indicated by their concentrations in biological samples obtained at different times from members of a Faroese birth cohort. (more ...)
Because of the pronounced association with the 18-months serum PCB concentration, which was obtained only for about one-fifth of the cohort, we conducted further analyses using the imputed data. These results strengthened the observations, and an inverse association was now apparent for tetanus at age 7 years ().
Table 5 Effect on antibody concentrations at ages 5 years (pre-booster) and 7 years associated with PCB exposures reflected by the serum concentration at 18 months after multiple imputation to allow for missing observations among the 587 members of a Faroese (more ...)
We further identified the children who had antibody concentrations below a clinically protective level of 0.1 IU/mL. As anticipated, the highest number was at the pre-booster examination at age 5 years, with 202 (37%) children having a low diphtheria concentration and 141 (26%) having a low tetanus concentration. The numbers of children with inadequate antibody concentrations were much less (7% and 4%, respectively) at age 7 years, 2 years after booster vaccination. The ORs for inadequate antibody concentrations associated with a doubling of PCB concentrations are shown in . In general, children showing insufficient protection against diphtheria had experienced higher PCB exposures, as reflected by the concentrations in milk and in serum concentrations at ages 18 months or 5 years. Among the limited number of children with available exposure data from age 18 months, the only two children with insufficient protection against diphtheria at age 7 years had PCB concentrations of 3.9 μg/g lipid and 5.3 μg/g lipid—among the five highest in the group, a statistically significant deviation (p = 0.04) from an expectation of no association.
ORs (95% CIs) and p-values describing the effect of a doubling exposure concentration on the risk of an antibody concentration below a clinically protective level of 0.1 IU/mL in Faroese birth cohort members examined at ages 5 and 7 years (n = 587).
Mercury exposure parameters showed variable associations with the antibody concentrations without a clear pattern. The strongest negative association was for the hair-mercury concentration at age 5 years with regard to the diphtheria antibody concentration at age 7 years (−16.3; 95% CI, −31.3 to 1.9; p = 0.08), but this association was substantially attenuated when adjusted for PCB (−5.6; 95% CI, −23.9 to 17.2; p = 0.60). Adjustment for mercury had only a negligible effect on the regression coefficients for PCB (data not shown).