April 14, 2008 — Childhood asthma is reduced by half when the first dose of diphtheria, pertussis, and tetanus (DPT) is delayed by more than 2 months vs given during the recommended period, according to the results of a retrospective longitudinal study reported in the March issue of the Journal of Allergy & Clinical Immunology.

"Early childhood immunizations have been viewed as promoters of asthma development by stimulating a T _H 2-type immune response or decreasing microbial pressure, which shifts the balance between T _H 1 and T _H 2 immunity," write Kara L. McDonald, MSc, from the University of Manitoba in Winnipeg, Manitoba, Canada, and colleagues. "Differing time schedules for childhood immunizations may explain the discrepant findings of an association with asthma reported in observational studies. This research was undertaken to determine whether timing of diphtheria, pertussis, tetanus (DPT) immunization has an effect on the development of childhood asthma by age 7 years."

The investigators analyzed data from the complete immunization and healthcare records of a cohort of children born in Manitoba in 1995, from birth until age 7 years. Using multivariable logistic regression, they computed the adjusted odds ratio for asthma at age 7 years according to the timing of DPT immunization.

Among 11,531 children who received at least 4 doses of DPT, the risk for asthma was halved in children in whom administration of the first dose of DPT was delayed by more than 2 months. For children with delays in administration of all 3 doses, the likelihood of asthma was 0.39 (95% confidence interval [CI], 0.18 - 0.86).

"We found a negative association between delay in administration of the first dose of whole-cell DPT immunization in childhood and the development of asthma; the association was greater with delays in all of the first 3 doses," the study authors write. "The mechanism for this phenomenon requires further research."

Limitations of this study include possible ascertainment bias; findings not yet confirmed with the diphtheria, acellular pertussis, tetanus (DaPT) vaccine; and inability to refute the issue of early-life infections as an explanation for the association between delayed immunization and protection against the development of asthma.

"Further study is vital to gain a detailed understanding of the relationship between vaccination and allergic disease, because a perception that vaccination is harmful may have an adverse effect on the effectiveness of immunization programs," the study authors conclude.

The Canadian Institutes of Health Research supported this study. Some of the authors have disclosed various financial relationships with the Western Regional Training Center for Health Services Research, the National Training Program in Allergy and Asthma, the Canadian Institutes of Health Research, Allergen, and/or Novartis.

J Allergy Clin Immunol. 2008;121:626-631.

Clinical Context

Study Highlights

• Of children born in Manitoba in 1995, 11,531 children (82.6%) had received at least 4 doses of DPT and were included in this study.
• These children were primarily immunized with whole-cell pertussis DPT, because the DaPT vaccine was phased in throughout Manitoba beginning in November 1997.
• The investigators analyzed data from the complete immunization and healthcare records of these children from birth until age 7 years.
• The investigators used multivariable logistic regression to compute the adjusted odds ratio (OR) for asthma at age 7 years, based on the timing of whole-cell DPT immunization.
• Prevalence of asthma was 11.7%.
• Children with asthma were predominantly boys (3:2) and lived in urban areas (70.3%); 25% were from low-income homes; and 10.1% had mothers with a history of asthma.
• The risk for asthma was decreased by 50% in children in whom administration of the first dose of DPT was delayed by more than 2 months (OR, 0.50; 95% CI, 0.25 - 0.97).
• Sensitivity analyses that varied the interval for DPT immunization showed that these findings were robust.
• Asthma prevalence rates decreased successively from 13.8% to 5.9% with each month delay in DPT administration.
• Likelihood of childhood asthma was also decreased after delays in the administration of the second and third doses of DPT. Most of these delays were in children with delays in their first dose.
• The reduction in asthma risk for the second and third doses mainly resulted from the delay in the first dose because there were no statistically significant differences in asthma risk with delays in the second and third doses in the absence of delays in the first dose.
• However, for children with delays in administration of all 3 doses, the likelihood of asthma was further reduced by 60% (likelihood ratio, 0.39; 95% CI, 0.18 - 0.86).
• Based on these findings, the investigators conclude that there was a negative association between delay in administration of the first dose of DPT immunization in childhood and the development of asthma; that the association was greater with delays in all of the first 3 doses; and that the underlying mechanism requires further research.
• Limitations of this study include possible ascertainment bias; findings not yet confirmed with the DaPT vaccine; and inability to refute the issue of early-life infections as an explanation for the association between delayed immunization and protection against the development of asthma.

Pearls for Practice

• Among children who received at least 4 doses of DPT, the risk for asthma was reduced by 50% in children in whom administration of the first dose of DPT was delayed by more than 2 months from the recommended period.
• For children with delays in administration of all 3 doses of DPT, the risk of developing asthma was decreased by 60%. The reduction in asthma risk for the second and third doses mainly resulted from the delay in the first dose.

CME Test