Childhood Vaccinations and Risk of Asthma

Frank Destefano, MD; David Gu, PhD; Piotr Kramarz, MD; Benedict I. Truman, MD; Michael F. Iademarco, MD; John P. Mullooly, PhD; Lisa A. Jackson, MD; Robert L. Davis, MD; Steven B. Black, MD; Henry R. Shinefield, MD; S. Michael Marcy, MD; Joel I. Ward, MD; Robert T. Chen, MD; The Vaccine Safety Datalink Research Group

Pediatr Infect Dis J. 2002;21(6) 

In This Article

Abstract and Introduction

Background: A few previous studies have suggested that childhood vaccines, particularly whole cell pertussis vaccine, may increase the risk of asthma. We evaluated the suggested association between childhood vaccinations and risk of asthma.
Methods: Cohort study involving 167 240 children who were enrolled in 4 large health maintenance organizations during 1991 to 1997, with follow-up from birth until at least 18 months to a maximum of 6 years of age. Vaccinations were ascertained through computerized immunization tracking systems, and onset of asthma was identified through computerized data on medical care encounters and medication dispensings.
Results: In the study 18 407 children (11.0%) developed asthma, with a median age at onset of 11 months. The relative risks (95% confidence intervals) of asthma were: 0.92 (0.83 to 1.02) for diphtheria, tetanus and whole cell pertussis vaccine; 1.09 (0.9 to 1.23) for oral polio vaccine; 0.97 (0.91 to 1.04) for measles, mumps and rubella (MMR) vaccine; 1.18 (1.02 to 1.36) for Haemophilus influenzae type b (Hib); and 1.20 (1.13 to 1.27) for hepatitis B vaccine. The Hib result was not consistent across health maintenance organizations. In a subanalysis restricted to children who had at least 2 medical care encounters during their first year, the relative risks decreased to 1.07 (0.71 to 1.60) for Hib and 1.09 (0.88 to 1.34) for hepatitis B vaccine.
Conclusion: There is no association between diphtheria, tetanus and whole cell pertussis vaccine, oral polio vaccine or measles, mumps and rubella vaccine and the risk of asthma. The weak associations for Hib and hepatitis B vaccines seem to be at least partially accounted for by health care utilization or information bias.

Asthma is the most common chronic disease of childhood in developed countries, and its prevalence has been increasing.[1,2] It has been suggested that infant and childhood vaccinations may be contributing to the increasing prevalence of asthma.[3,4,5,6] The strongest evidence in support of a possible association between vaccination and asthma comes from a prospective study of a cohort of children born in 1977 in Christchurch, New Zealand.[4] In that study there was no evidence of asthma after 5 to 10 years of follow-up among 23 children who received neither pertussis nor oral polio vaccine, whereas asthma developed in >20% of 1184 children who had been vaccinated. A study of 1934 patients followed from birth to age 12 in a general medical practice in the UK found an ~1.4-fold increased risk of asthma associated with whole cell pertussis vaccination.[7] An association between pertussis vaccination and asthma was also reported in two cross-sectional surveys.[5,8] No association was found, however, in a Swedish clinical trial involving 669 children.[9]

There are theoretical reasons to suspect a possible association of asthma with vaccination. One possible mechanism is that vaccines or their adjuvants may have direct IgE-potentiating effects.[10,11,12,13] Another possibility is that vaccination may shift the immunologic balance toward a more allergenic response.[14] It has also been suggested that vaccination may indirectly affect the tendency to develop allergies and perhaps asthma, by preventing diseases in childhood, such as measles, which may protect against developing allergic conditions later in life.[15,16] In the case of pertussis the disease has been suggested to increase the occurrence of atopy and asthma, and it may be that the vaccine could have similar effects.[9,17,18]

Because vaccination is universally recommended for infants, any association between childhood vaccinations and the occurrence of a common serious condition such as asthma could be of considerable public health importance. We performed a study using the combined data resources of four large health maintenance organizations (HMOs) to evaluate the associations between vaccines and the occurrence of asthma in childhood. We were primarily interested in associations with diphtheria, tetanus and whole cell pertussis (DTP) and measles, mumps and rubella (MMR) vaccines. For completeness we also evaluated the other routinely recommended childhood vaccines.

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