BMJ  2004;328:925-926 (17 April), doi:10.1136/bmj.38045.858889.EB (published 19 March 2004)

Paper

Pertussis vaccination in infancy and asthma or allergy in later childhood: birth cohort study

¹ Bristol Royal Hospital for Children, Department of Respiratory Medicine, Bristol BS2 8BJ, ² Avon Longitudinal Study of Parents and Children, University of Bristol, Department of Community-based Medicine, Bristol BS8 1TQ, ³ St Michael's Hospital, Ear, Nose, and Throat Department, Bristol BS2 8EG

Introduction

Some studies have shown a link between vaccination of infants with whole cell inactivated pertussis vaccine and the later development of asthma and atopy.^{1 2} A randomised controlled trial disagreed with these findings, but follow up was done until only 30 months of age.³ Our previous report of the lack of an association between pertussis vaccination and wheezing disorders was based on outcomes in early childhood.⁴ In this study we have examined the association between pertussis vaccination in infancy and asthma or atopy by age 7.5 years in a large, population based birth cohort.

Participants, methods, and results

Participants were the 13 971 children who survived to 1 year in the Avon longitudinal study of parents and children. The study method has been described previously,⁵ and details can be found on the study website (www.alspac.bris.ac.uk). We obtained the vaccination status for each child from the child health surveillance database. We categorised children with regard to pertussis as fully vaccinated (completed a primary course of diphtheria, tetanus, and pertussis vaccination), partially vaccinated (completed a primary course of diphtheria and tetanus but did not receive pertussis vaccine) or non-vaccinated (no vaccinations). We excluded other combinations from analysis. We obtained three wheezing outcomes based on parental self report questionnaires (asthma at 69-81 months, wheeze with whistling on the chest at 69-81 months, and asthma diagnosed by a doctor at 91 months) and one atopy outcome based on skin prick tests at age 7 years. We defined atopy as one or more positive reactions (wheal 2 mm) to a panel of three common allergens. We selected several variables as potential confounders of the relation between exposure and outcome, which were, however, not considered to be in the causal pathway. These were, from mother's questionnaire data: maternal education, maternal smoking during pregnancy, maternal history of asthma or eczema, maternal financial difficulties, damp housing, overcrowding, child's ethnicity, number of siblings, contact with cats in the home, duration of breast feeding, and passive exposure to tobacco smoke; and, from medical records: birth weight, sex, gestational age, and maternal age at delivery. We used Pearson's ² (or Fisher's exact test if the predicted number of subjects in any category was less than five) for our data analysis of univariable associations between vaccination status and possible confounders and principal outcomes. We used multivariable logistic regression models to evaluate associations between immunisation status and asthma and allergy outcomes while controlling for potential confounders.

Vaccination history was available for 13 810 children, of whom 13 109 (94.9%) were fully vaccinated, 446 did not have pertussis vaccination (340 non-vaccinated; 106 partially vaccinated), and 255 had some other combination. The table shows numbers of subjects with outcome data for each of the principal outcomes. The cumulative prevalence of asthma diagnosed by doctors was 20.3% (n = 1597) at 91 months. The prevalence of reported asthma at 69-81 months was 12.4% (n = 1024), reported wheeze with whistling at 69-81 months 9.8% (n = 798) and atopy at 7 years 20.5% (n = 1324). The table shows the adjusted and unadjusted odds ratios and 95% confidence intervals from logistic regressions for each of the principal outcomes. Although unadjusted analyses showed significant associations (asthma at 69-81 months, P = 0.05; doctor diagnosed asthma, 91 months, P = 0.005), it should be noted that, because of small numbers in some groups, the confidence intervals were wide and the results did not support the hypothesis. When we adjusted for potential confounding factors we detected no significant associations (P = 0.1-0.8).

View this table: [in this window] [in a new window]   Odds ratios with 95% confidence intervals for outcome variables according to pertussis vaccination status

 

Comment

These findings confirm and extend our previous observations of the lack of an independent association between pertussis vaccination in infancy with inactivated, whole cell vaccine and the subsequent development of asthma or atopy during later childhood.

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A supplemental table is on bmj.com

This article was posted on bmj.com on 19 March 2004: http://bmj.com/cgi/doi/10.1136/bmj.38045.858889.EB

Acknowledgments: We thank the mothers and children who took part and the midwives for their cooperation and help in recruitment. The whole ALSPAC study team comprises interviewers, computer technicians, laboratory technicians, clerical workers, research scientists, volunteers, and managers who continue to make the study possible. The ALSPAC study is part of the European Longitudinal Study of Parents and Children initiated by the World Health Organization.

Contributors: MG had the original idea. AM, AS, JH did the analysis. All authors contributed to the interpretation of the data. AM wrote the paper. JH will act as guarantor.

Funding: Core funding for the long term follow up of the cohort came from the Medical Research Council, the Wellcome Trust, the UK Department of Health, the Department of the Environment, DfEE, the National Institutes of Health, and a variety of medical research charities. No specific funding was obtained for this analysis.

Competing interests: None declared.

Ethical approval: Avon Longitudinal Study of Parents and Children Ethics and Law Committee.

References

1. Odent MR, Kimmel T. Pertussis vaccination and asthma: is there a link? JAMA 1994;272: 592-593.
2. Kemp T, Pearce N, Fitzharris P, Crane J, Fergusson D, St George I, Wickens K, Beasley R. Is infant immunization a risk factor for childhood asthma or allergy? Epidemiology 1997;8: 678-680.[CrossRef][Web of Science][Medline]
3. Nilsson L, Kjellman N-IM, Björksten B. A randomised controlled trial of the effect of pertussis vaccines on atopic disease. Arch Pediatr Adolescent Med 1998;152: 734-738.[Abstract/Free Full Text]
4. Henderson AJ, North K, Griffiths M, Harvey I, Golding J, ALSPAC Study Team. Pertussis vaccination and wheezing illnesses in young children: prospective cohort study. BMJ 1999;318: 1173-1176.[Abstract/Free Full Text]
5. Golding J, Pembrey M, Jones R., ALSPAC Study Team. ALSPAC—the Avon longitudinal study of parents and children I. Study methodology. Paediatr Perinatal Epidemiol 2001;15: 74-87.[CrossRef][Web of Science][Medline]

(Accepted 8 December 2003)

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