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


A total of 167 240 children were included in the analysis, of whom 18 407 (11.0%) developed asthma according to our case definition. ~77% (14 237 of 18 407) of the cases met the first criterion (at least one asthma diagnosis and one prescription for an asthma medication). Overall the median age at last follow-up was 28 months, and the asthma cases had a median age of 11 months on their incidence date. Children who developed asthma were more likely to be male and to have had a low birth weight ( Table 1 ).

Vaccination coverage was high in our study population. Only a small proportion of children had no record in the automated immunization tracking systems of receiving DTP, OPV or Hib vaccines ( Table 2 ). Nonetheless the total population was so large that even the small proportion not vaccinated resulted in an absolute number of 6069 children who did not receive DTP vaccine. DTP and OPV were often administered together; only 3400 children (2.0%) had no record of receiving either vaccine. Only 400 children received acellular pertussis vaccine as their first pertussis vaccination. Among the children not vaccinated with OPV, none received inactivated polio vaccine. A relatively large proportion of children apparently did not receive MMR or hepatitis B vaccines. The MMR coverage partially reflects the fact that many of the children had an asthma incidence date before the recommended age for MMR vaccination (12 to 15 months). The first years of our study covered the period when recommendations for universal infant vaccination against hepatitis B were first issued, and the lower hepatitis B vaccination coverage probably reflects delays in implementation of these recommendations.

In the proportional hazards regression analyses, we found that DTP, OPV and MMR were not associated with an increased risk of developing asthma in infancy or childhood ( Table 3 ). The relative risks for Hib and hepatitis B vaccine were 1.18 and 1.20, respectively, with 95% confidence intervals that excluded 1.0. The point estimate of the relative risk for hepatitis B vaccine was >1.0 at each of the HMOs, whereas the Hib relative risk was >1.0 only at NCK and <1.0 at the other HMOs.

We also evaluated the effect of the number of doses of a vaccine and found that after the first dose of each of the vaccines of interest the relative risks were similar to those after a second or subsequent dose of the vaccine (data not shown).

In the subanalysis in which we included additional adjustments for Census block indicators of race, ethnicity and socioeconomic factors, the results were little changed from those presented in Table 3 . A total of 116 496 children were included in this subanalysis and the relative risks (95% confidence interval) were 0.96 (0.85 to 1.10) for DTP, 1.00 (0.92 to 1.08) for MMR, 1.14 (0.97 to 1.35) for Hib and 1.16 (1.08 to 1.25) for hepatitis B vaccine.

In the subanalysis in which we used a case definition intended to identify more severe cases of asthma, the relative risks were not materially different from the results of our main analysis. In this analysis, which required a hospital discharge or emergency room visit diagnosis of asthma as part of the case definition, the number of cases decreased to 4164 (from 18 407 in the main analysis). The largest change in the relative risk was for DTP vaccine, which decreased to 0.77 (0.63 to 0.94) compared with 0.92 (0.83 to 1.02) in the main analysis. The relative risks for Hib and hepatitis B vaccines remained elevated at 1.32 (0.99 to 1.76) and 1.15 (1.03 to 1.29), respectively.

To assess the influence of medical care utilization, we performed a subanalysis according to number of medical care encounters during the first year of life. This analysis required availability of computerized outpatient clinic encounters data, which were only completely available at GHC from 1992 through 1996 and at NCK for 1995 and 1996. Among the entire group of 17 949 children included in this subanalysis, regardless of number of encounters, the relative risks for all of the vaccines ( Table 4 ) were generally similar to the results of the main analysis ( Table 3 ). When the analysis was restricted to the 17 740 children at NCK and GHC who had at least 2 medical encounters during their first year of life, the relative risks for both Hib and hepatitis B vaccines, as well as OPV, decreased and the relative risks for the other vaccines were unchanged ( Table 4 ).

In the subanalysis restricted to children who had received at least two doses of OPV, two doses of DTP and one dose of MMR by age 18 months, the relative risk of asthma among children who also received hepatitis B vaccine compared with those who had not received hepatitis B vaccine was 1.12 (1.05 to 1.20).


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