Developmental exposure to polychlorinated biphenyls (PCBs) has been implicated as a possible cause of deficient immune function in children. This study was designed to assess whether prenatal and postnatal exposure to PCBs impacts on antibody response to childhood immunizations.
Methods and Findings
Two birth cohorts were formed in the Faroe Islands, where exposures vary widely, because traditional diets may include whale blubber contaminated with PCBs. Prenatal exposure was determined from maternal concentrations of PCBs in pregnancy serum and milk. Following routine childhood vaccinations against tetanus and diphtheria, 119 children were examined at 18 mo and 129 children at 7 y of age, and their serum samples were analyzed for tetanus and diphtheria toxoid antibodies and for PCBs. The antibody response to diphtheria toxoid decreased at age 18 mo by 24.4% (95% confidence interval [CI], 1.63–41.9; p = 0.04) for each doubling of the cumulative PCB exposure at the time of examination. The diphtheria response was lower at age 7 y and was not associated with the exposure. However, the tetanus toxoid antibody response was affected mainly at age 7 y, decreasing by 16.5% (95% CI, 1.51–29.3; p = 0.03) for each doubling of the prenatal exposure. Structural equation analysis showed that the early postnatal exposure was the most important predictor of a decreased vaccination response.
Increased perinatal exposure to PCBs may adversely impact on immune responses to childhood vaccinations. The clinical implications of insufficient antibody production emphasize the need for prevention of immunotoxicant exposures.
A study of two birth cohorts in the Faroe Islands, where diets may include whale blubber contaminated with polychlorinated biphenyls (PCBs), suggests exposure to PCBs may reduce immune response to childhood vaccinations.
These days, mothers are as likely to worry about potential side-effects of childhood vaccinations as about whether they completely protect their child against infections. But healthy children vary in how well vaccinations “take.” After tetanus and diphtheria vaccination, for example, some children produce large quantities of antibodies that protect them against these serious bacterial diseases; others make a weaker, sometimes inadequate, immune response. What causes this variation is unclear, but one possibility is that the developing immune system is damaged in some babies by exposure both before birth and after birth through breast milk to “immunotoxicants” such as polychlorinated biphenyls (PCBs). These stable, man-made chemicals, which were widely used last century as insulators in electrical equipment and as fire retardants, accumulate and persist in the environment where they affect animal and human health. PCB-exposed babies often have a small thymus (the gland where immune system cells mature), make decreased amounts of antibodies, and have more childhood infections.
Why Was This Study Done?
Given these observations, could exposure to PCBs be partly responsible for the variable immunological responses of children to vaccination? If it is, and if environmental PCB levels remain high, it might be necessary to adapt more intensive vaccination programs so that all children are adequately protected against infectious diseases. In this study, the researchers examined whether prenatal and postnatal exposure to PCBs affects antibody responses to childhood vaccinations
What Did the Researchers Do and Find?
The researchers enrolled two groups of children—one group born in 1994–1995, the other in 1999–2001—living on the Faroe Islands in the North Atlantic. Here, people are exposed to high levels of PCBs through eating contaminated whale blubber. All the children received routine vaccinations against diphtheria and tetanus. The bacteria that cause these illnesses do so by producing a “toxoid,” so a harmless quantity of these toxic proteins is injected to stimulate a protective antibody response. For the older group, a blood sample was taken when they were seven and half years old to test for antibodies against diphtheria and tetanus toxoids; for the younger group, a sample was taken at 18 months. The exposure of the children to PCBs was assessed by measuring PCBs in their mothers' blood during pregnancy, in their mothers' milk soon after birth, and in their own blood when their antibodies were tested. The researchers found that the antibody response to diphtheria toxoid in the younger group of children was reduced by nearly a quarter for every doubling in their total exposure to PCBs. The tetanus toxoid response in the older children was reduced by a similar amount by prenatal exposure to PCBs. Although most of the children made enough antibodies to both toxoids to provide protection, about a fifth of the older children—mainly those with the highest exposures to PCBs—had worryingly low levels of diphtheria toxoid antibodies.
What Do These Findings Mean?
These results reveal an association between exposure to PCBs, particularly soon after birth, and a reduction in immunoprotection after childhood vaccinations. It is not clear, however, exactly how big this effect may be. This is uncertain for two reasons. First, the estimates of how much antibody responses are reduced by doubling PCB exposure are imprecise—for the younger children this change in exposure might actually have very little effect on their response to diphtheria vaccination or it could halve their response. Second, the estimates of PCB exposures are based on only three samples of body fluids so provide only a crude indication of exposure. Nevertheless, these results in children exposed to high levels of PCBs indicate that the immune function of children might also be adversely affected by the lower levels of PCBs found elsewhere in the world. Although the changes in immune function are subtle, they could be clinically important, write the researchers, and might affect both the general health of children and the degree of protection against infectious diseases that vaccination provides. Finally, these findings suggest that efforts must be stepped up to reduce PCB exposure levels to protect the sensitive immune systems of young children from these potent immunotoxicants.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0030311.
Tox Town, a Web site available from the US National Institutes of Health, provides an introduction to toxic chemicals and environmental health risks
US Agency for Toxic Substances and Disease Registry fact sheet on PCBs
US Environmental Protection Agency information on PCBs
MedlinePlus encyclopedia entries on immunization tetanus vaccine, and diphtheria vaccine
Wikipedia pages on PCBs and vaccines (note: Wikipedia is a free online encyclopedia that anyone can edit)