Is health, growth and development impaired in children who are Hepatitis B-exposed but uninfected?

An estimated 254 million people are living with chronic hepatitis B virus (HBV) infection worldwide. Many infants are born to mothers with HBV but do not themselves acquire the infection. It is unclear whether this exposure to HBV in early life - without the development of active infection - may be associated with adverse outcomes. We propose the term "HBV-exposed uninfected (HBEU)", drawing parallels with the HIV field which recognises that children who are HIV-exposed but uninfected face an increased risk of adverse health outcomes. This paper explores the potential health consequences for children HBEU. We summarise existing evidence reporting on children HBEU, and also review existing knowledge from the HIV field that could inform insights. We hypothesise that children HBEU may be at increased risk of preterm birth, and/or impaired growth and neurodevelopmental delay, but comprehensive, longitudinal studies are currently lacking to support this. We propose a conceptual framework to hypothesise how exposure to HBV could potentially lead to adverse growth and neurodevelopment through both HBV-specific and universal pathways, and review the available evidence and research gaps. Data are needed to establish whether short- and long-term sequelae exist for children HBEU, and to inform evidence-based interventions to mitigate against detrimental outcomes. Establishing a comprehensive understanding of the long-term trajectory of health and well-being among children HBEU throughout childhood into adolescence will require longitudinal observational studies with appropriate control groups to characterise outcomes, identify risk factors and explore underlying mechanistic pathways.