Lower risk of atopic disorders in whole cell pertussis-vaccinated children

An increased risk of atopic disorders in pertussis or diphtheria tetanus pertussis (DTP) vaccinated children has been reported 1–4, but this was not confirmed by more recent observational studies 5–7, a randomised placebo-controlled trial 8, and an ecological study 9. Reports of adverse effects of vaccinations usually cause controversy and debate between advocates and opponents of vaccination programmes. The current study evaluated the role of the pertussis vaccination as a risk factor for atopic disorders within a study of family size and birth order as risk factors for asthma, allergy and eczema in a population of 700 families in the Netherlands.

Material and methods

Results

The 700 families comprised 1,961 children. Both vaccination status and atopic status was available for 1,724 children; of these 44 (2.6%) were not vaccinated for pertussis, mostly for religious reasons. Of these, 39 had received no vaccinations at all, four received only the polio-vaccination, and one received DT‐polio (without pertussis). The 1,724 children had their health checkup at a mean age of 5.9 yrs (sd: 0.6 yrs). The types of allergy mentioned were house-dust mite, pollen, furry pets, food allergy, hay fever and allergic rhinitis. The prevalence of atopic disorders in both groups is shown in table 1⇓. Crude odds ratios (OR)s for atopic disorders (vaccinated/unvaccinated) varied between 0.33–0.69. Adjusted ORs ranged 0.23–0.40, consistent with a substantially reduced risk of atopy in pertussis-vaccinated children. The same analysis in the subgroup of children attending orthodox reformed schools (39 unvaccinated and 128 vaccinated children) yielded similar point estimates. For “any atopic disorder” the adjusted OR (vaccinated/unvaccinated) in this subgroup was 0.16 (95% confidence interval 0.04–0.67, data not shown in table).

Discussion

In the present study, pertussis-vaccinated children were at a considerably lower risk of atopic disorders than unvaccinated children. Most vaccinated children received the combined DTP‐polio vaccine. Hence, the comparison of children with and without pertussis vaccination was almost equivalent to the comparison of DTP‐polio vaccination and no vaccination at all. Data used for this study were not collected to answer the present research question, and consequently no sample sizes for vaccinated and unvaccinated groups were computed. A total of 44 unvaccinated children were found and the relations studied were significant. Adjustment for confounders could have been a problem with so few children at risk, with resulting empty cells and huge confidence intervals. However, this was not the case and the results of the adjusted analyses showed similar relations. All data were collected retrospectively from files and possibly misreporting, most likely underreporting, of atopic diseases may have occurred. It could be that this misclassification is differential, i.e. related to the risk factor under study. This may mean that parents of vaccinated children report less atopy than unvaccinated children. However, the relations found persisted and even became somewhat stronger when the analyses were restricted to the more homogenous group of children attending orthodox reformed schools. Even if within this more homogenous group underreporting would be differential, it would be more likely that parents of unvaccinated children (more orthodox religious families) would report less than parents of vaccinated children. However, this bias would lead to an attenuation of the OR and the unbiased OR would even be more extreme.

In the Netherlands pertussis is endemic in childhood and shows 4‐yearly peaks 12. The highest incidence is reported ininfants aged <1 yr (35 per 100,000 per year during 1989–1993). Pertussis cases are reported both in vaccinated and unvaccinated children, the incidence in the latter group being roughly 10‐fold the incidence in the vaccinated group. The relatively low incidence in the unvaccinated group (compared to completely unvaccinated groups in Germany) can be explained by herd immunity.

As only 0.7% of the study population was born after 1997, the role of acellular pertussis vaccine is negligible in this study.

Given the hygiene hypothesis, it would be expected that the immune system of the unvaccinated children would have shifted more towards the T‐helper cell 1‐side, inconsistent with a raised risk of atopy. On the other hand, the immune system of vaccinated children is triggered with the (albeit killed) microorganisms at a very young age and from this point of view the findings of the current study fit in the hygiene hypothesis and are biologically plausible.

The findings of the current study are consistent with a recent study in Germany by Grüber et al. 7. Several studies found an increased risk of asthma and allergy in DTP or pertussis-vaccinated children 1–4, but this may be due to residual confounding or confounding by indication as the reasons for not vaccinating are not described and may be related to the outcome. A number of studies found no relation between the DTP or the pertussis-vaccination and atopy 5–9. One of these is a randomised controlled trial 8, which compared three groups that received different cocktails of DTP with a control group that received DT only. However the age of evaluation at 2.5 yrs was rather young and this may account for the lack of an effect. Henderson et al. 5 found no difference, but in this study the outcome was wheezing at the age of not more than 42 months. All (but one) studies mentioned above are observational and residual confounding cannot be excluded, especially when the reason for refraining from vaccination is not known. It is important for future studies to include groups that are as homogenous as possible and adequately describe the differences between vaccinated and unvaccinated groups.