Hepatitis B vaccination of preterm infants and risk of bronchopulmonary dysplasia: a cohort study, Australia

Objective To determine whether hepatitis B virus (HBV) vaccination of extremely preterm infants (defined in our study as < 29 weeks gestation) within 24 hours of birth (birth-dose) increases the risk of developing bronchopulmonary dysplasia. Methods Using data from Australia, we conducted a population data linkage study using the Victorian Vaccine Safety Health Link. This platform links state-wide immunization and health outcomes from theVictorian Perinatal Data Collection and theVictorian Admitted Episodes Dataset. Our retrospective cohort study included all extremely preterm infants born alive during 2017-2020 (excluding data outliers). We investigated the relationship between birth-dose HBV vaccination and bronchopulmonary dysplasia diagnosis at 36 weeks postmenstrual age. We identified possible confounders using a directed acyclic graph, and included these confounders in a robust Poisson regression model. Findings Of the 818 extremely preterm infants meeting our inclusion criteria, 306 received birth-dose HBV vaccination: 50.7% (155/306) of the vaccinated and 61.9% (317/512) of the unvaccinated infants developed bronchopulmonary dysplasia. After accounting for measured confounders, the adjusted relative risk was 0.83 (95% confidence interval, CI: 0.68-1.00), suggesting no increased risk. However, residual confounding by indication may still be present as it is not known how clinician perception ofthe stability ofthe newborn affects the decision to vaccinate or not, potentially underestimating any association between vaccination and outcome. Conclusion Ourfindings support existing World Health Organization recommendationsto immunizeall infantsagainst HBVwithin 24 hours of birth, including those born prematurely.