Title:
Impact of maternal carrier status on immunologic markers for protection after hepatitis B vaccination in infancy: a meta-analysis.

Abstract:
Better protection against hepatitis B infection in offspring of carrier mothers has been postulated because of a booster effect by close maternal contact. Empirical evidence, however, is inconclusive. Immunologic markers for protection against hepatitis B are anti-HBs ≥ 10 mIU/ml or response to booster in case anti-HBs had fallen below 10 mIU/ml. The objective of this paper was to asses whether immunologic markers suggest a higher protection after hepatitis B vaccination in offspring of carrier mothers. A systematic review was performed in order to identify all studies in offspring of carrier and non-carrier mothers reporting the proportions of individuals with anti-HBs ≥ 10 mIU/ml after infant hepatitis B vaccination with a presently recommended dose in children aged 5 years or older or response to a booster dose in case anti-HBs was below 10 mIU/ml. Associations between carrier status and the proportions of anti-HBs ≥ 10 mIU/ml or booster response were analysed by random effects models with adjustment for age and potential confounders. We identified 19 studies providing proportions of anti-HBs ≥ 10 mIU/ml with explicit information regarding the maternal carrier status. These studies reported 3245 children of carrier mothers aged up to 20 years and 4602 children of non-carrier mothers aged up to 14 years. Antibody titres ≥ 10 mIU/ml were detected in 75.8% of children of carrier and 63.6% of non-carrier mothers. A random effects model with adjustment for confounding yielded an odds ratio of 2.43 (95% CI 1.24-4.75) suggesting a markedly higher probability of anti-HBs ≥ 10 mIU/ml in offspring of carrier compared to non-carrier mothers. The distribution of proportions of individuals with post booster increase of anti-HBs titres ≥ 10 mIU/ml stratified by age at booster (≤ 10 years and >10 years) showed no differences between offspring of carrier and non carrier mothers up to the age of 10 years and only marginal differences thereafter. In conclusion the proportions of anti-HBs ≥ 10 mIU/ml were clearly higher in offspring of carrier mothers years after infant vaccination but there appeared to be no clinically relevant difference in response to booster. It is unclear to which extent higher proportions of breakthrough infections contribute to the higher proportions of protective antibody titres in offspring of carrier mothers.