No Evidence for Disease History as a Risk Factor for Narcolepsy after A(H1N1)pdm09 Vaccination.
To investigate disease history before A(H1N1)pdm09 vaccination as a risk factor for narcolepsy.



Case-control study in Sweden. Cases included persons referred for a Multiple Sleep Latency Test between 2009 and 2010, identified through diagnostic sleep centres and confirmed through independent review of medical charts. Controls, selected from the total population register, were matched to cases on age, gender, MSLT-referral date and county of residence. Disease history (prescriptions and diagnoses) and vaccination history was collected through telephone interviews and population-based healthcare registers. Conditional logistic regression was used to investigate disease history before A(H1N1)pdm09 vaccination as a risk-factor for narcolepsy.



In total, 72 narcolepsy cases and 251 controls were included (range 3-69 years mean19-years). Risk of narcolepsy was increased in individuals with a disease history of nervous system disorders (OR range = 3.6-8.8) and mental and behavioural disorders (OR = 3.8, 95% CI 1.6-8.8) before referral. In a second analysis of vaccinated individuals only, nearly all initial associations were no longer statistically significant and effect sizes were smaller (OR range = 1.3-2.6). A significant effect for antibiotics (OR = 0.4, 95% CI 0.2-0.8) and a marginally significant effect for nervous system disorders was observed. In a third case-only analysis, comparing cases referred before vaccination to those referred after; prescriptions for nervous system disorders (OR = 26.0 95% CI 4.0-170.2) and ADHD (OR = 35.3 95% CI 3.4-369.9) were statistically significant during the vaccination period, suggesting initial associations were due to confounding by indication.



The findings of this study do not support disease history before A(H1N1)pdm09 vaccination as a risk factor for narcolepsy.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Favelle
F
Lamb
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Alexander
A
Ploner
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Katharina
K
Fink
CAST (Centre for allogenic stem cell transplantation), Karolinska Hospital, Stockholm, Sweden.|Division of Therapeutic Immunology (TIM), LabMed Karolinska Institutet, Stockholm, Sweden.
Markus
M
Maeurer
Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet and Karolinska University Hospital, Huddinge, Stockholm, Sweden.
Peter
P
Bergman
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Fredrik
F
Piehl
Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, The Netherlands.
Daniel
D
Weibel
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Pär
P
Sparén
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Lisen Arnheim
LA
Dahlström
D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage*; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009290:Narcolepsy / Q000150:complications / Q000175:diagnosis* / Q000503:physiopathology; D009422:Nervous System Diseases / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy / Q000503:physiopathology; D016017:Odds Ratio; D012042:Registries; D012307:Risk Factors; D013548:Sweden; D014611:Vaccination / Q000706:statistics & numerical data*
D007252:Influenza Vaccines