Hepatitis B vaccine alone or with hepatitis B immunoglobulin in neonates of HBsAg+/HBeAg- mothers: a systematic review and meta-analysis

J Antimicrob Chemother. 2015 Feb;70(2):396-404. doi: 10.1093/jac/dku404. Epub 2014 Oct 31.


Objectives: The cost-effectiveness of augmenting immunization against hepatitis B infection with hepatitis B immunoglobulin (HBIG) remains controversial, particularly for the subpopulation of babies of HBsAg+/HBeAg- mothers that are considered as low-infective. We aimed to evaluate the effectiveness of vaccine alone compared with vaccine plus HBIG for the immunization of babies of HBsAg+/HBeAg- mothers.

Methods: We searched PubMed, Scopus and Cochrane Central Register of Controlled Trials databases to identify studies comparing the effectiveness of combined immunization (vaccine plus HBIG) with vaccine alone in neonates of HBsAg+/HBeAg- mothers. A systematic review and meta-analysis of eligible studies was performed.

Results: A total of nine eligible studies were identified (four randomized controlled trials). No difference was found regarding the primary outcome of our meta-analysis, namely occurrence of hepatitis B infection, between neonates who received vaccine only, compared with those who received both vaccine and HBIG (four studies, 3426 patients, OR=0.82, 95% CI=0.41-1.64). This finding was consistent with regards to seroprotection rate (four studies, 1323 patients, OR=1.24, 95% CI=0.97-1.58). Safety data were not reported in the included studies.

Conclusions: The available limited published evidence suggests that vaccine alone seems to be equally effective to the combination of HBIG and hepatitis B vaccine for neonates of HBsAg+/HBeAg- mothers in preventing infection. Further studies are needed in order to clarify the potential benefit of combined immunization to this specific subgroup of patients.

Keywords: HBV; hepatitis B virus; immunization.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Hepatitis B / epidemiology
  • Hepatitis B / prevention & control*
  • Hepatitis B / transmission*
  • Hepatitis B Surface Antigens / blood*
  • Hepatitis B Vaccines / immunology*
  • Humans
  • Immunoglobulins / blood*
  • Infant
  • Infant, Newborn
  • Infectious Disease Transmission, Vertical / prevention & control*
  • Infectious Disease Transmission, Vertical / statistics & numerical data
  • Odds Ratio
  • Patient Outcome Assessment


  • Hepatitis B Surface Antigens
  • Hepatitis B Vaccines
  • Immunoglobulins
  • hepatitis B hyperimmune globulin