Immunisation, Hepatitis and Blood Safety Department, Health Protection Agency, Colindale, London NW9 5EQ, UK.
BMJ. 2013 Feb 26;346:f794. doi: 10.1136/bmj.f794.
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.
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.
Sleep centres and paediatric neurology centres in England.
Children and young people aged 4-18 with onset of narcolepsy from January 2008.
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.
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.
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.
评估 2009 年甲型 H1N1 大流行疫苗（Pandemrix）在英格兰针对接种 ASO3 佐剂的儿童和青少年中引发嗜睡症的风险。
回顾性分析。2011 年 8 月至 2012 年 2 月间，从医院病历中提取睡眠测试的临床信息和结果，并由专家小组进行审查以确认诊断。疫苗接种和临床病史均从全科医生处获得。
英格兰的睡眠中心和儿科神经病学中心。
2008 年 1 月以来发病的 4-18 岁儿童和青少年。
调整了接种疫苗的临床指征后，比较嗜睡症患者与同期英格兰人群的疫苗接种几率。使用病例对照研究方法，测量接种疫苗后 6 个月内与该期间以外的嗜睡症发生率。
共审查了 245 名儿童和青少年的病历记录；75 名患有嗜睡症（56 名伴有猝倒），发病时间在 2008 年 1 月以后。11 名患者在发病前已接种疫苗，其中 7 名在发病前 6 个月内接种。在 2011 年 7 月前确诊的患者中，任何时间点接种疫苗的比值比为 14.4（95%置信区间 4.3 至 48.5），发病前 6 个月内接种疫苗的比值比为 16.2（3.1 至 84.5）。在 2011 年 7 月前确诊的患者中，自发病时间为 2008 年 10 月至 2010 年 12 月的病例对照研究分析中，相对发病率为 9.9（2.1 至 47.9）。估计归因风险为每 57500 至 52000 剂疫苗 1 例。
接种 ASO3 佐剂的甲型 H1N1 大流行疫苗后嗜睡症风险增加表明存在因果关系，与芬兰的发现一致。然而，由于诊断延迟的变化，接种疫苗的儿童更快就诊可能会高估风险。
