title: Exploring the risk factors for vaccine-associated and non-vaccine associated febrile seizures in a large pediatric cohort.
abstract: BACKGROUND
  It is not known whether there are underlying physiologic or immunologic differences between febrile seizures (FS) triggered by vaccines versus other causes. Furthermore, while secular and individual-level factors have been associated with FS risk, they are rarely evaluated simultaneously.
  
  
  METHODS
  Subjects included members of Kaiser Permanente Southern California aged 6 months to 3 years from July 1, 2003-December 31, 2011. Primary outcome was first diagnosis of FS. Vaccine-associated (VA) FS were defined as those occurring from day 0 to day 15 following any vaccine; non-vaccine associated (NVA) FS were those outside this period. We compared incidence rates of VA-FS versus NVA-FS. Poisson regression was used to assess the association between FS and secular and individual-level factors. We also evaluated interactions between vaccine exposure and each model covariate on the risk of FS.
  
  
  RESULTS
  Among 265,275 children, 3348 FS were identified; 383(11%) were VA-FS, and 2965(89%) were NVA-FS. Incidence rates were 2.73 and 2.05 per 100,000 person-days for VA-FS and NVA-FS, respectively. Multivariable analyses confirmed previously reported increased risk of FS by age, low gestational age, and winter months. Increased risk was also associated with VA exposure (RR=1.63[95% CI: 1.27-2.11]), non-White race/ethnicity vs. White (African-American RR=1.41[1.22-1.63]; Asian RR=1.58[1.40-1.79]; Hispanic RR=1.60[1.47-1.75]), and maternal age 29 years or less vs. 40+ years (≤ 19 years RR=1.28[1.00-1.65]; 20-29 years RR=1.21[1.02-1.42]). Females were at lower risk of NVA-FS (RR=0.77[0.72-0.83]), but were similar to males for VA-FS (RR=0.97[0.79-1.19]). Children with low 1 min Apgar scores (≤ 3) had increased risk of VA-FS (RR=3.40[1.86-6.22]), but no increased risk for NVA-FS (RR=1.05[0.69-1.60]) compared to children with normal Apgar scores (≥ 7).
  
  
  CONCLUSIONS
  This study suggests that there may be immunogenetic differences underlying VA-FSs compared with other FSs. However, further studies are needed. An understanding of the mechanisms behind these findings may help improve vaccine design or policies.
authors.affiliation: Kaiser Permanente Southern California, Department of Research & Evaluation, USA. Electronic address: sara.y.tartof@kp.org.
authors.forename: Sara Y
authors.initials: SY
authors.lastname: Tartof
authors.affiliation: Kaiser Permanente Southern California, Department of Research & Evaluation, USA. Electronic address: Hung-fu.X.Tseng@kp.org.
authors.forename: Hung Fu
authors.initials: HF
authors.lastname: Tseng
authors.affiliation: Kaiser Permanente Southern California, Department of Research & Evaluation, USA. Electronic address: Amy.L.Liu@kp.org.
authors.forename: Amy L
authors.initials: AL
authors.lastname: Liu
authors.affiliation: Kaiser Permanente Southern California, Department of Research & Evaluation, USA. Electronic address: Lei.X.Qian@kp.org.
authors.forename: Lei
authors.initials: L
authors.lastname: Qian
authors.affiliation: Kaiser Permanente Southern California, Department of Research & Evaluation, USA. Electronic address: lina.s.sy@kp.org.
authors.forename: Lina S
authors.initials: LS
authors.lastname: Sy
authors.affiliation: Kaiser Permanente Southern California, Department of Research & Evaluation, USA. Electronic address: Rulin.C.Hechter@kp.org.
authors.forename: Rulin C
authors.initials: RC
authors.lastname: Hechter
authors.affiliation: Kaiser Permanente Southern California, Department of Research & Evaluation, USA. Electronic address: smmarcy@labiomed.org.
authors.forename: S Michael
authors.initials: SM
authors.lastname: Marcy
authors.affiliation: Kaiser Permanente Southern California, Department of Research & Evaluation, USA. Electronic address: steven.j.jacobsen@kp.org.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Jacobsen
mesh_terms: D001724:Birth Weight; D002140:California; D002675:Child, Preschool; D015331:Cohort Studies; D005006:Ethnicity; D005260:Female; D005865:Gestational Age; D006801:Humans; D007223:Infant; D008297:Male; D008423:Maternal Age; D015999:Multivariate Analysis; D012307:Risk Factors; D003294:Seizures, Febrile / Q000139:chemically induced / Q000209:etiology*; D014612:Vaccines / Q000009:adverse effects*
chemical_list: D014612:Vaccines
keywords: Febrile convulsion; Febrile seizures; Interaction; Risk factors; Vaccination