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. 2012 Sep 17:345:e5823.
doi: 10.1136/bmj.e5823.

Use of population based background rates of disease to assess vaccine safety in childhood and mass immunisation in Denmark: nationwide population based cohort study

Thomas A Rasmussen  1 , Martin R S Jørgensen, Stephanie Bjerrum, Søren Jensen-Fangel, Henrik Støvring, Lars Østergaard, Ole S Søgaard
Affiliations

Use of population based background rates of disease to assess vaccine safety in childhood and mass immunisation in Denmark: nationwide population based cohort study

Thomas A Rasmussen et al. BMJ. .

Abstract

Objectives: To predict the number of selected outcomes temporally associated but not caused by vaccination, to aid causality assessment of adverse events arising after mass immunisation in a paediatric population.

Design: Nationwide population based cohort study.

Setting: Denmark.

Participants: All liveborn infants delivered after 1 January 1980. Study population was followed from date of birth until hospital admission for selected outcome diagnoses, death, first emigration, age 18 years, or 31 December 2009. The study population was subject to vaccines used in standard childhood immunisation in Denmark, with 82-93% vaccine coverage.

Main outcome measures: Incidence of acute infectious and post-infectious polyneuritis (Guillain-Barré syndrome), acute transverse myelitis, optic polyneuritis, facial nerve palsy, anaphylactic shock, seizure, multiple sclerosis, autoimmune thrombocytopenia, type 1 diabetes mellitus, juvenile and rheumatoid arthritis, narcolepsy, and death of unknown cause stratified by sex, age, and season. We predicted the number of events for a hypothetical vaccine cohort of 1,000,000 people for follow-up periods of up to 182 days.

Results: The study included 2,300,227 liveborn infants, yielding 37,262,404 person years of follow-up; median follow-up was 16.8 person years. Incidence of outcome diagnoses spanned from 0.32 per 100,000 patient years for autoimmune thrombocytopenia to 189.82 per 100,000 patient years for seizure. Seasonal differences were most pronounced for anaphylactic shock, seizure, and multiple sclerosis. Even for rare outcomes, numerous events were predicted in the hypothetical vaccine cohort. We predicted that 20 cases of type 1 diabetes mellitus, 19 of juvenile or rheumatoid arthritis, eight of facial nerve palsy, and five of multiple sclerosis per 1,000,000 children would occur within 42 days after vaccination.

Conclusions: Incorporating exact background rates of disease based on age, sex, and seasonal distribution could strengthen vaccine safety assessment, and provides an evidence based focus for discussing the incremental risk of newly introduced vaccines.

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Conflict of interest statement

Competing interests: All authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: support from Aarhus University Hospital for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous 3 years; no other relationships or activities that could appear to have influenced the submitted work.

Figures

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Fig 1 Annual birth counts and annual deaths before age 5 years
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Fig 2 Seasonal distribution of incidence (per 100 000 person years) of selected outcome diagnoses. Data are shown for each quarter of the year
See this image and copyright information in PMC

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