Risk of narcolepsy in children and young people receiving AS03 adjuvanted pandemic A/H1N1 2009 influenza vaccine: retrospective analysisBMJ 2013; 346 doi: https://doi.org/10.1136/bmj.f794 (Published 26 February 2013) Cite this as: BMJ 2013;346:f794
- Elizabeth Miller, consultant epidemiologist1,
- Nick Andrews, senior statistician2,
- Lesley Stellitano, public health researcher13,
- Julia Stowe, research fellow14,
- Anne Marie Winstone, public health researcher13,
- John Shneerson, consultant physician5,
- Christopher Verity, consultant paediatric neurologist13
- 1Immunisation, Hepatitis and Blood Safety Department, Health Protection Agency, Colindale, London NW9 5EQ, UK
- 2Statistics, Modelling, and Economics Department, Health Protection Agency, Colindale, London NW9 5EQ, UK
- 3PIND Research Group, Addenbrooke’s Hospital, Cambridge CB2 0QQ, UK
- 4General and Adolescent Paediatric Unit, Institute of Child Health, University College London, London NW1 2PF, UK
- 5Respiratory Support and Sleep Centre, Papworth Hospital, Cambridge CB23 3RE, UK
- Correspondence to: E Miller
- Accepted 30 January 2013
Objective To evaluate the risk of narcolepsy in children and adolescents in England targeted for vaccination with ASO3 adjuvanted pandemic A/H1N1 2009 vaccine (Pandemrix) from October 2009.
Design Retrospective analysis. Clinical information and results of sleep tests were extracted from hospital notes between August 2011 and February 2012 and reviewed by an expert panel to confirm the diagnosis. Vaccination and clinical histories were obtained from general practitioners.
Setting Sleep centres and paediatric neurology centres in England.
Participants Children and young people aged 4-18 with onset of narcolepsy from January 2008.
Main outcome measures The odds of vaccination in those with narcolepsy compared with the age matched English population after adjustment for clinical conditions that were indications for vaccination. The incidence of narcolepsy within six months of vaccination compared with the incidence outside this period measured with the self controlled cases series method.
Results Case notes for 245 children and young people were reviewed; 75 had narcolepsy (56 with cataplexy) and onset after 1 January 2008. Eleven had been vaccinated before onset; seven within six months. In those with a diagnosis by July 2011 the odds ratio was 14.4 (95% confidence interval 4.3 to 48.5) for vaccination at any time before onset and 16.2 (3.1 to 84.5) for vaccination within six months before onset. The relative incidence from the self controlled cases series analysis in those with a diagnosis by July 2011 with onset from October 2008 to December 2010 was 9.9 (2.1 to 47.9). The attributable risk was estimated as between 1 in 57 500 and 1 in 52 000 doses.
Conclusion The increased risk of narcolepsy after vaccination with ASO3 adjuvanted pandemic A/H1N1 2009 vaccine indicates a causal association, consistent with findings from Finland. Because of variable delay in diagnosis, however, the risk might be overestimated by more rapid referral of vaccinated children.
We thank Douglas Fleming, Royal College of General Practitioners, for supplying the RCGP data extracts for the vaccine coverage estimates and Stephen Evans, London School of Hygiene and Tropical Medicine, for review of the statistical analysis plan. The authors gratefully acknowledge the participation of Paul Gringras, Evelina Children’s Hospital, St Thomas’ Hospital, London, and Zenobia Zaiwalla, Sleep Disorders Service, John Radcliffe Hospital, Oxford, in the expert panel. We thank the members of the British Sleep Society and the British Paediatric Neurology association, and the general practitioners who assisted with the follow-up. The HES data are re-used with permission of the Health and Social Care Information Centre.
Contributors: All the authors were involved in study design. JS, CV, AMW, and LS extracted clinical information from the centre notes. JS extracted the HES cases and conducted the GP follow-up. JSh assisted in recruitment of sleep centres and was a member of the expert panel. NA conducted the statistical analysis, and EM wrote the first draft of the paper. All authors contributed to the final version and had access to the dataset.
Funding: The study was funded by the Department of Health policy research programme and the Health Protection Agency. The views expressed in the publication are those of the authors and not necessarily those of the Department of Health, England. The funding source had no role in data collection, data analysis, data interpretation, or writing of the report. CV, JS, AMW, and LS were supported by a grant from the Department of Health research and development directorate (No 039/0031).
Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.
Ethical approval: HPA has approval for England from the National Information Governance Board for Health and Social Care (NIGB) (PIAG ref: PIAG 03-(c)/2001), which allows us access to patient identifiable information for purposes of monitoring vaccine safety.
Data sharing: No additional data available.
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