Hepatitis B vaccine and the risk of CNS inflammatory demyelination in childhood

Neurology. 2009 Mar 10;72(10):873-80. doi: 10.1212/01.wnl.0000335762.42177.07. Epub 2008 Oct 8.


Background: The risk of CNS inflammatory demyelination associated with hepatitis B (HB) vaccine is debated, with studies reporting conflicting findings.

Methods: We conducted a population-based case-control study where the cases were children with a first episode of acute CNS inflammatory demyelination in France (1994-2003). Each case was matched on age, sex, and geographic location to up to 12 controls, randomly selected from the general population. Information on vaccinations was confirmed by a copy of the vaccination certificate. The odds ratios (ORs) of CNS inflammatory demyelination associated with HB vaccination were estimated using conditional logistic regression.

Results: The rates of HB vaccination in the 3 years before the index date were 24.4% for the 349 cases and 27.3% for their 2,941 matched controls. HB vaccination within this period was not associated with an increase in the rate of CNS inflammatory demyelination (adjusted OR, 0.74; 0.54-1.02), neither >3 years nor as a function of the number of injections or brand type. When the analysis was restricted to subjects compliant with vaccination, HB vaccine exposure >3 years before index date was associated with an increased trend (1.50; 0.93-2.43), essentially from the Engerix B vaccine (1.74; 1.03-2.95). The OR was particularly elevated for this brand in patients with confirmed multiple sclerosis (2.77; 1.23-6.24).

Conclusions: Hepatitis B vaccination does not generally increase the risk of CNS inflammatory demyelination in childhood. However, the Engerix B vaccine appears to increase this risk, particularly for confirmed multiple sclerosis, in the longer term. Our results require confirmation in future studies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bias
  • Case-Control Studies
  • Child
  • Data Collection
  • Data Interpretation, Statistical
  • Demyelinating Diseases / epidemiology*
  • Female
  • France / epidemiology
  • Hepatitis B Vaccines / adverse effects*
  • Humans
  • Inflammation / epidemiology
  • Logistic Models
  • Male
  • Multiple Sclerosis / epidemiology
  • Odds Ratio
  • Risk
  • Socioeconomic Factors


  • Hepatitis B Vaccines