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Delaying DPT Vaccination May Reduce Incidence of Childhood Asthma
CME

News Author: Laurie Barclay, MD
CME Author: Laurie Barclay, MD
Disclosures

Release Date: April 14, 2008; Valid for credit through April 14, 2009

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 TH2-type immune response or
decreasing microbial pressure, which shifts the balance between TH1
and TH2 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

Early childhood vaccinations may promote development of asthma,
directly by stimulating a TH2-type immune response or indirectly by
decreasing microbial pressure. In support of this hypothesis, an IgE
response to vaccine antigens often occurs in children vaccinated with
diphtheria/tetanus, and this response is more pronounced among
individuals with atopy.

Epidemiologic evidence linking DPT immunizations to childhood asthma
is inconsistent. Some studies show an increased or decreased risk of
developing asthma, whereas others show no association. This study
assessed whether timing of DPT vaccination affects the risk of
developing childhood asthma by age 7 years.

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/CE Test
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