Timing of the First Dose of the Hepatitis B Vaccine in Preterm Infants

Abstract

Introduction: The World Health Organization (WHO) recommends all newborn infants receive the first dose of the hepatitis B vaccine within 24 h of birth irrespective of maternal hepatitis B carrier status. However, the physiological immaturity of the immune system in preterm infants may influence the immune responses to the vaccine particularly in the first few days and weeks of life, and adverse events may occur following vaccination that are not observed in infants born at term. Objectives: To review existing published guidelines surrounding timing of the first dose of the hepatitis B vaccine in preterm infants born to hepatitis B surface antigen negative (HBsAg-negative) mothers. Methods: A search was performed for relevant papers and guidelines published between January 2002 and July 2022 on the Ovid MEDLINE and Embase databases and through targeted searches. Two authors independently reviewed the search results to identify relevant sources, which were then analysed and described through narrative synthesis. Results: Twenty-seven relevant papers and guidelines regarding 15 countries and regions were included. Of these, 13.3% of guidelines, which represented 16.8% of the overall population of 4.1 billion people covered by the identified guidelines, recommended a nationwide birth dose of the hepatitis B vaccine to all preterm infants. In 40.0% of guidelines (77.9% of the overall population), the birth dose was only recommended for infants with a birth weight of more than 2000–2200 g. Another 33.3% of countries and regions (covering 4.4% of the population) recommended no universal birth dose for all infants, including preterm infants, whilst 13.3% (1.0% of the population) had guidelines that varied between jurisdictions and hospitals within their country/region. Conclusions: Existing guidelines surrounding the timing of the first dose of the hepatitis B vaccine in preterm infants vary substantially between countries and regions. Further research comparing the immunogenicity and safety of different hepatitis B vaccine schedules is needed to provide concrete evidence to provide guidance regarding the timing of vaccination against hepatitis B in preterm infants.

Safety of Hepatitis B Vaccines (Monovalent or as Part of Combination) in Preterm Infants: A Systematic Review

“…Birth dose hepatitis B vaccination policies for preterm infants are highly variable around the world [ 10 ]. Apart from the prevention of vertical transmission of hepatitis B—which of course is of critical importance, particularly in regions with high hepatitis B prevalence—there is no known added benefit of receiving a birth dose of the hepatitis B vaccine.…”

“…However, for the ~0.5% of neonates born prematurely who are at risk of BPD and for whom, therefore, hepatitis B vaccination at birth may carry an increased risk [ 8 ], there is a paucity of literature regarding the safety of this vaccine. Notably, guidelines in many regions with low hepatitis B prevalence and/or reliable antenatal screening programs and/or high vaccination rates in the first years of life already recommend not administering the birth dose to preterm infants (e.g., birth weight < 2000 g [ 10 ]). Given that the birth dose is not necessary for immunogenicity in preterm babies if a 12-month dose is used [ 31 ], the pragmatic approach already used in many regions appears sensible until reliable safety data are published.…”

“…In a previous systematic review [ 10 ], we noted that the timing of the first dose of the hepatitis B vaccine in preterm infants is highly variable around the world. Only 13% of the guidelines we identified and reviewed recommended a birth dose of the hepatitis B vaccine for all infants, regardless of prematurity.…”

“…Adverse events following immunisation (AEFIs) are untoward events that occur following vaccination, irrespective of causality, while adverse effects are those where causality has been established. Based on our previous paper [ 10 ], it is clear that the timing of hepatitis B vaccination around the world is variable, and these circumstances call for a look at the literature for the safety of hepatitis B vaccination at different time points of administration. Accordingly, we aimed to assess the safety of the hepatitis B vaccine (as a monovalent or a combination vaccine) in infants.…”

Time Interval Distribution of Hepatitis B Vaccine Immunization among Infants in China from 2017 to 2021

“…Studies measuring vaccine timeliness have become more frequent in recent years, and suggest that the first dose of hepatitis B vaccine should be administered within 24 hours of birth regardless of the mother's HBV status [6,[14][15][16][17][18], as recommend by the World Health Organization (WHO) [6].…”