Impact of lamivudine treatment in late pregnancy on the development of the foetal immune response to hepatitis B virus: a meta-analysis in R with the metafor package.

Background: Hepatitis B virus (HBV) infection is a worldwide public health burden, especially in Asia and Africa. Concerns were raised that foetal exposure to HBV and antiretroviral therapy (ART) might suppress the innate immune response and reduce the production of hepatitis B surface antibody (HBsAb) in foetuses and infants. We therefore conducted the current study to evaluate the impact of ART on the development of the immune response to HBV in foetuses and infants.

Methods: We selected lamivudine instead of telbivudine or tenofovir as the intervention measurement because it was the oldest and most widely used ART during pregnancy and its safety data have been sufficiently documented. A comprehensive search was conducted in eight electronic databases, including four Chinese and four English databases. Studies that met the following eligibility criteria were included: human randomized controlled trials (RCTs); participants in the treatment group were exclusively exposed to lamivudine; participants in the control group were exposed to placebo, no treatment or hepatitis B immunoglobulin; all participants were HBV-positive pregnant women with a high viral load and the main outcome of interest was neonatal HBsAb seropositivity. Data were tabulated and analysed using R software.

Results: Nine RCTs were included and analysed. Compared with controls, lamivudine significantly decreased HBsAb seronegativity in the newborn within 24 h after birth (indicating the foetal immune response to HBV). Similar results were noted in infants within 6-7 months after birth and infants within 12 months (indicating the neonatal immune response to HBV vaccine).

Conclusions: Lamivudine treatment in late pregnancy boosted the foetal immune response to HBV in utero and enhanced the neonatal immune response to hepatitis B vaccine after birth.